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AIMS Obesity is associated with high rates of cardiac fatty acid oxidation, low rates of glucose oxidation, cardiac hypertrophy and heart failure. Whether weight loss can lessen the severity of heart failure associated with obesity is not known. We therefore determined the effect of weight loss on cardiac energy metabolism and the severity of heart failure in obese mice with heart failure. MATERIALS AND METHODS Obesity and heart failure were induced by feeding mice a high-fat (HF) diet and subjecting them to transverse aortic constriction (TAC). Obese mice with heart failure were then switched for 8 weeks to either a low-fat (LF) diet (HF TAC LF) or caloric restriction (CR) (40% caloric intake reduction, HF TAC CR) to induce weight loss. RESULTS Weight loss improved cardiac function (%EF was 38 ± 6% and 36 ± 6% in HF TAC LF and HF TAC CR mice vs 25 ± 3% in HF TAC mice, P < 0.05) and it decreased cardiac hypertrophy post TAC (left ventricle mass was 168 ± 7 and 171 ± 10 mg in HF TAC LF and HF TAC CR mice, respectively, vs 210 ± 8 mg in HF TAC mice, P < 0.05). Weight loss enhanced cardiac insulin signalling, insulin-stimulated glucose oxidation rates (1.5 ± 0.1 and 1.5 ± 0.1 μmol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 ± 0.1 μmol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPKTyr172 /ACCSer79 signalling and the acetylation of s-oxidation enzymes, were attenuated following weight loss. CONCLUSIONS Weight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.

Summary Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.

Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

Background The preferred reperfusion strategy for ST-segment elevation myocardial infarction (STEMI) is percutaneous coronary intervention (PCI) provided it can be performed in a timely fashion at an expert 24/7 facility. However, many Canadians reside in areas precluding timely transport to a specialized facility. A new regional PCI facility could be economically viable if implementation costs are at least comparable to urgent transportation and interventional team clinical competency is maintained. Objectives Provide a cost economic model for assisting decisions regarding addition of a regional PCI facility. Methods We used the following in the model: (1) PCI laboratory construction costs, (2) ambulance transportation costs, (3) procedural costs, and (4) expected clinical volume. We compared expected per PCI cost of air transportation vs deploying a regional facility based on population and distance from an existing centre. Results Potential cost economic advantages exist for establishing new PCI centres with decreasing minimum populations of 208,100, 141,900, and 110,000 located at increasing distances of 150 km, 300 km, and 450 km, respectively, from the existing tertiary PCI centres. Sensitivity analyses suggest that regions with modest populations of approximately 200,000 located at these distances may be economically attractive. Conclusions The derived algorithm can be used to assess the economics component of establishing regional PCI laboratories and identify opportunities for extending access for primary PCI. This model presents a means for evaluating the economic implications of constructing a new facility. Additional components such as staffing and patient preferences for location of care also require consideration.

Heart failure (HF) clinics are known to improve outcomes of patients with HF. Studies have been limited to single, usually tertiary centres whose experience may not apply to the general HF population.To determine the effectiveness of HF clinics in reducing death or all-cause rehospitalization in a real-world population.A retrospective analysis of the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) disease registry was performed. All 8731 patients with a diagnosis of HF (844 managed in HF clinics) who were discharged from the hospital between October 15, 1997, and July 1, 2000, were identified. Patients enrolled in any one of four HF clinics (two community-based and two academic-based) were compared with those who were not. The primary outcome was the one-year combined hospitalization and mortality.Patients followed in HF clinics were younger (68 versus 75 years), more likely to be men (63% versus 48%), and had a lower ejection fraction (35% versus 44%), lower systolic blood pressure (137 mmHg verus 146 mmHg) and lower serum creatinine (121 micromol/L versus 130 micromol/L). There was no difference in the prevalence of hypertension (56%), diabetes (35%) or stroke/transient ischemic attack (16%). The one-year mortality rate was 23%, while 31% of patients were rehospitalized; the combined end point was 51%. Enrollment in an HF clinic was independently associated with reduced risk of total mortality (hazard ratio [HR] 0.69 [95% CI 0.51 to 0.90], P=0.008; number needed to treat for one year to prevent the occurrence of one event [NNT]=16), all-cause hospital readmission (HR 0.27 [95% CI 0.21 to 0.36], P0.0001; NNT=4), and combined mortality or hospital readmission (HR 0.73 [95% CI 0.60 to 0.89], P0.0015; NNT=5).HF clinics are associated with reductions in rehospitalization and mortality in an unselected HF population, independent of whether they are academic- or community-based. Such clinics should be made widely available to the HF population.

Background Spironolactone use for heart failure (HF) has increased dramatically after the publication of the Randomized Aldactone Evaluation Study trial; yet, few studies have examined its real-world impact. We aimed to determine the population effect of spironolactone use on mortality in HF patients discharged from hospital. Methods and Results All patients discharged alive between October 1997 and December 2001 in Nova Scotia, Canada, with a primary diagnosis of HF were enrolled in the Improving Cardiovascular Outcomes Study. Two year, all-cause mortality was the primary end point. A total of 7816 patients were identified, of whom 644 (8%) were discharged home on spironolactone. After adjusting for differences in clinical covariates, spironolactone use did not emerge as an independent predictor of long-term survival (OR 0.97, P = .80). When only the subgroup of patients enrolled in a HF clinic were included (n = 990), spironolactone use was associated with reduced rates of all-cause mortality at 2 years (OR 0.52, P = .003). Conclusions Although spironolactone use was not associated with improved long-term survival in the general HF population, it was associated with improved long-term survival in patients enrolled in HF clinics. These data highlight the challenges of knowledge translation from a clinical trial into practice.

It has been hypothesized that angiotensin-converting enzyme (ACE) inhibition, independent from its effect on ventricular function and blood pressure, could affect the atherosclerotic process and reduce the incidence of ischemic events and its complications. Several large clinical outcome trials were designed to test this hypothesis: QUIET, HOPE, EUROPA, PEACE, and IMAGINE. The results of the PEACE study were recently reported, leaving the IMAGINE study as the last chapter in our efforts to evaluate the role of ACE inhibition in coronary artery disease with preserved left ventricular function. In this report, we compare these studies with respect to their methodology and patient population and analyze the unique nature of the last ongoing study, IMAGINE. The reported studies show that patients with coronary artery disease who are at low-to-moderate or high risk should receive an ACE inhibitor if tolerated. However, when the absolute risk of a patient decreases, and intensive contemporary management is given, with good control of risk factors, the absolute and perhaps relative benefits of an ACE inhibitor decrease and their routine use in these patients may not be warranted. The role of ACE inhibition started early post-coronary artery bypass graft in patients with preserved left ventricular function, and intensive contemporary management remains to be determined and should get answered by the IMAGINE study. Moreover, the IMAGINE population is not only a lower risk population than those enrolled in HOPE or EUROPA, but also the risk for this population is bimodal in nature (early post-revascularization inflammation and thrombosis vs long-term atherosclerosis progression) and may provide further insight into underlying mechanisms.

Between 1984 and 1993, prevalence and case fatality of hospitalized acute myocardial infarction (AMI) had declined in the population of Halifax County. We aimed to determine whether these trends continued into the 21st century by investigating patient characteristics, treatment methods, and fatality for hospital admissions of residents of Halifax County, aged 25–74, during 1984–1989 (period 1), 1990–1993 (period 2), and 1998–2001 (period 3) and diagnosed as AMI that were extracted from databases for the Halifax County MONICA and ICONS (Improving Cardiovascular Outcomes in Nova Scotia) Studies. Trends in patient characteristics and treatment methods were assessed by χ2 statistics. Their association with 28-day fatality was determined by logistic regression. Event rate declined during 1984–1993 but not into 1998–2001 (p = 0.206). Compared with 1990–1993, fewer AMI patients during 1998–2001 were ≥55 years (73.3% vs. 69.9%), cigarette smokers (49.8% vs. 42.9%), had a history of myocardial infarction (28.9% vs. 24.9%), and had an admission heart rate >100 (34.8% vs. 17.4%). Additionally, more patients had a history of diabetes (22.5% vs. 28.1%). Case fatality declined progressively over the 3 study time periods (16.6%, 13.1%, and 9.4%, respectively). Changes also occurred in prevalence of Killip class 4 status during admission (20.2%, 10.3%, and 13.3%, respectively), use of thrombolysis (9.0%, 30.9, and 32.6%, respectively), and percutaneous coronary intervention (PCI) (4.3%, 11.2%, and 22.4%, respectively) in the different periods. Significant associations were found between case fatality and patient history of diabetes, history of MI, age, elevated admission heart rate, Killip class 4 impairment, thrombolysis, and PCI. The ICONS registry of hospitalized acute myocardial infarctions was used to compare case fatality during 1998–2001 with that reported by the Halifax County MONICA Project for 1984–1993. Whereas the population rate of myocardial infarctions had declined between 1984–1993 but not subsequently, case fatality declined significantly throughout the study period. The continued decline in case fatality is likely explained by changes in patient profile on presentation and medical therapies, including the increased use of thrombolysis and PCI.

Background Complementary and alternative medical (CAM) therapies are becoming increasingly popular, yet little information is available about the prevalence and patterns of CAM therapy use by patients with cardiovascular disease (CVD). Methods Interviewers administered telephone questionnaires to 107 patients randomly selected from a stratified cohort of 2487 eligible patients participating in a registry of patients with CVD. Results The current use of CAM therapies was reported by 64% of the patients surveyed. Nutritional supplements (40%) and megadose vitamins (35%) were the most frequently used preparations. Most CAM therapy users (65%) cited their underlying cardiac condition as the reason for taking such therapy. The most common sources of information about CAM were a friend or relative (43%) or the respondent’s usual physician. However, although 80% of respondents claimed that they had discussed their use of CAM therapies with their physician, 58% of respondents taking a potentially toxic cardiovascular medication (digoxin, warfarin, sotalol, or amiodarone) were simultaneously taking an oral supplement. Conclusion The use of CAM therapies was high in the cohort of patients surveyed. Physicians caring for patients with CVD need to inquire about CAM therapy use. Further scientific study should be performed to evaluate the potential benefits and risks of CAM therapies in this patient population.

Background— Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. Methods and Results— We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death ( P P P =0.024 for interaction of group by treatment). Conclusion— Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

After the 2009 publication of Building a Heart Healthy Canada, the Canadian Cardiovascular Society was commissioned to address a long-standing information gap related to the compatibility and comparability of data on the quality of cardiovascular care in Canada. Through collaboration between the Canadian Institute for Health Information, the Institute for Clinical Evaluative Sciences, the Public Health Agency of Canada, and 5 regional cardiovascular registries, 2 committees were tasked with developing standardized cardiovascular data definitions and quality indicators. The work culminated in national consensus on the definitions of 55 patient, disease, and therapeutic variables (core and optional) to facilitate cardiovascular care comparisons within and across Canada. Supplemental data definition chapters were then developed on acute coronary syndrome and coronary angiography/revascularization, with chapters on heart failure and atrial fibrillation electrophysiology to follow. This foundational work led to a critical appraisal of cardiac quality indicator development initiatives via the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Quality Indicator tool, followed by the development of quality indicator catalogues on heart failure and atrial fibrillation. These indicators will be embedded within the clinical practice guidelines of the Canadian Cardiovascular Society, facilitating national comparisons across Canada on cardiovascular disease incidence, prevalence, patterns and quality of care, and clinical outcomes. This methodology-achieving national stakeholder consensus on a standardized process for the development and selection of cardiovascular quality indicators-illustrates the capacity to reach agreement by drawing on expertise and research across diverse organizational mandates and agendas, potentially contributing to improved cardiovascular care and outcomes for patients.

The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD.To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150;50 yr) vs. late-onset CAD (n = 150;65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4.The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4.Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.

Aims Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. Methods and results C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. Conclusion We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes.

Background Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. Methods and Results In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH ( P =0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, P =0.006) and of congestive heart failure (9.3% versus 15.4%, P Conclusions The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure.

Last fall, the Editors of the journal Congestive Heart Failure, Drs. Marc Silver and John Strobeck, asked me to serve as Guest Editor for an issue of the journal. Accepting this honor was linked to the requirement that I had to generate a meaningful theme. The thought of delivering another series of articles on CHF trials and their interpretation, bench-to-bedside (and vice-versa) topics in heart failure, and similar efforts did little to excite me and, in fact, it threatened to exacerbate my narcoleptic condition. Besides, we have many colleagues more skilled at delivering this information and they truly enjoy doing so. We have fortunately entered the era of “evidence-based medicine” this theme will likely remain with us for the entire lifetime of health care delivery. While most physicians have now joined this movement, it is remarkable how much of the day-to-day medical care of the patient with heart failure has not yet been addressed by statistically powered (i.e., evidence-based) trials. Much (probably most) of what we do to keep patients as healthy and functional as possible is still based on our experience as clinicians and on the information shared by colleagues (personal contact, consultation, conferences, written material). It is not often that data from a large treatment trial assist me in determining the optimal dose of a drug or doses of combinations in an individual patient, in optimizing the immediate care and management of a complexly ill patient, in addressing the emergency phone call at 2 a.m., and so forth. Until statistically powered trials can address all aspects and details of patient care, “experience-based medicine” must fill the knowledge void. Unfortunately, much of this information is not available in textbooks, review articles, the Internet and other media. As the passionate fervor of evidence-based medicine soars to its fever pitch, there will be even less incentive to share in print potentially helpful information based on clinical experience. In his submission to this issue, Thomas D. Giles, MD, wrote, “I am fearful that valuable contributions to patient care will be lost and sacrificed on the altar of ‘evidenced-based’ medicine (usually referring to data from clinical trials). While I certainly believe that important concepts emanate from clinical trials, I also believe that there are other sources of guidance for the care of patients. The Reverend Bayes reminded us that intuition and prior experience are an integral part of the analysis of data.” Parenthetically, most of the questions addressed by trials and the design of trials are largely based on information gleaned from clinical experience. It is in this spirit that the Editors, Drs. Silver and Strobeck, CHF, Inc., and I present to you the first installment in a four-part series. The fuel for this project has both a historical and a pragmatic thrust; “it would be a shame” if we allowed our venerable colleagues to advance into the autumn of their careers or even retire without learning about their insights, thoughts, and passions regarding patient care, which grew out of decades of focused, intense clinical experience. Instead of less, we need to hear more from Drs. Chatterjee, Cohn, Armstrong, and colleagues. This series is not intended to serve as a comprehensive treatise on the management of heart failure. In fact, the authors assume that the reader is reasonably well versed in this area of study and practice. The content of each author's submission was not substantially altered by the editors and staff. Any disagreements that we and fellow coauthors may have regarding any submission were set aside so as to allow a free and open rendering of views and opinions. We are asking you, the reader, to judge and decide for yourself which of the “nuggets and pearls” are palatable and useful in your practice and in the day-to-day care of your patients afflicted with heart failure. To give you a better sense of the format and content of this series, I am sharing with you the directive I sent to each author in the letter of invitation: I would like you to contribute a piece on helpful tips, suggestions, maneuvers, and approaches that have been helpful to you (and your patients) over the years in the evaluation, management, and therapy of CHF. Everything is fair game. Much of the material will not have been previously published and is certainly not yet evidence-based. Basically, much of what we do in our day-to-day management of CHF patients is still related to simple clinical experience, doing what works, and our own ‘tricks of the trade.’ It is my intent to get these ideas, experiences, and thoughts into print. The publication should serve as a rich source of clinical insight, experience, and information, and perhaps will serve as a springboard for further studies and evidence-generating trials. With the exception of the deadline, there are absolutely no rules (referring to the usual editorial instructions for authors) for your submission! With the hundreds of heart failure experts located across this country and Canada, the selection of authors was a serious challenge. The selection targeted physician-scientists with at least two decades of heart failure experience, a significant publication record of peer-reviewed investigation in heart failure, and known, masterful clinical expertise in human heart failure at the bedside. Under the directive of the Guest Editor and taking advantage of my own lack of discretion, I added my name to the list of authors. A few of those invited could not contribute to the manuscript, thus accounting for the absence of certain authors. The Editors and I deeply apologize to those who were not invited to contribute because of our inadvertent oversight. If this venture is successful and well received, you are likely to be part of similar endeavors planned over the coming years. The coauthors and I dedicate this collection of insights and views to our teachers, who have collectively consisted of our patients, students, colleagues, and mentors. I thank Dr. Silver and Dr. Strobeck for this honor, and I thank my esteemed coauthors and colleagues for making this an educational and enjoyable experience for me.

Background Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction. Methods and Results PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions ≤35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 ( P =.002) for all-cause mortality, 2.55 ( P =.003) for cardiovascular mortality, 2.55 ( P =.005) for hospitalization for heart failure, 1.88 ( P =.002) for development of heart failure, 1.92 ( P =.001) for ischemic events, and 2.59 ( P =.005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events. Conclusions Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity.

Objectives . This study sought to assess the impact of delaying coronary artery bypass surgery at one Canadian academic tertiary referral center. Background . Universal access to medical services in Canada comes at the expense of waiting lists whose impact has been incompletely assessed. Methods . A prospective, observational study of all residents of Nova Scotia and Prince Edward Island accepted for bypass surgery between 1 April 1992 and 31 October 1992 was undertaken to determine 1) whether triage guidelines were being followed; and 2) the incidence of cardiac death, nonfatal myocardial infarction and worsening symptoms associated with delayed operation. The analysis had 90% power to detect a mortality rate of ≥3% (alpha 0.05). Results . Of 423 patients referred, 35% were triaged as urgent, 9.7% as semiurgent A, 39% as semiurgent B and 16.3% as elective, with no age or gender bias identified. Operation occurred at ≤1 week in 25%, ≤1 month in 47%, and >6 months in 1.4%. There were no nonfatal myocardial infarctions, but five cardiac deaths occurred (1.2%). Of 275 patients not initially classified as urgent, 12.4% required reclassification to higher priorities because of worsening symptoms: none had perioperative myocardial infarction or died. One in four patients queued longer than target waiting times. Only 4% of patients considered prioritization on the basis of medical need unfair, but 64% experienced at least moderate anxiety. Conclusions . This triage system equitably stratified patients to a queue. Deaths were rare and could not be attributed to the triage process. Patients with worsening clinical status were safely accommodated with earlier waiting times, but concerns remain regarding excessive waiting times and patient anxiety.

Background— The Alberta Cardiac Access (ACA) initiative was implemented in the spring of 2008 to increase access to specialized heart failure (HF) clinics after hospital discharge. Methods and Results— We identified all adults hospitalized with a most responsible diagnosis of HF between April 1999 and December 2009. We randomly selected 1 episode of care per patient and evaluated outcomes using interrupted time series: the a priori specified primary outcome was all-cause readmission or death in the first 30 days postdischarge. Between 1999 and 2009, median length of stay increased from 8 days to 10 days ( P P P =0.008). After roll out of the ACA initiative, patients discharged from vanguard regions (those that had specialized HF clinics) exhibited lower 30-day postdischarge death/readmission rates than those discharged from other areas of the province (18.6% versus 22.2%, adjusted odds ratio 0.83, 95% confidence interval, 0.75–0.93). Conclusions— An initiative which increased specialized HF clinic access was associated with a statistically significant improvement in 30-day postdischarge mortality/readmission rates.

A working group was convened by the Canadian Cardiovascular Society (CCS) in 2010 to identify quality indicators (QIs) for heart failure (HF). Using the CCS "Best Practices for Developing Cardiovascular Quality Indicators" methodology, a total of 49 "long-list" QIs was identified and rated. Subsequent ranking and discussion led to the selection of an initial "short-list" of 6 QIs to evaluate quality care, including daily assessment of blood chemistry indicators, chest radiography, patient education, in-hospital use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, assessment of left ventricular function, and 30-day hospital readmission. The short-list QIs were selected as being important for quality assurance and because the patient information, for the most part, can be captured during the inpatient setting, which would allow these QIs to be adopted more easily. These 6 QIs were subjected to a feasibility test that found that even within the inpatient setting, there is a significant gap between the existing knowledge infrastructure and the necessary information-tracking processes to measure QIs. Only 1 QI (30-day hospital readmission) can currently be measured comparatively across Canada, although the other 5 of 6 short-list QIs can be measured using other data collected by jurisdictions. Standardization and enhancements to knowledge infrastructure are essential to provide the comprehensive patient data necessary to evaluate the quality of HF care across Canada.

The aim of this study was to compare the long-term effects of treatment with enalapril or placebo on plasma neurohormones in patients with left ventricular (LV) dysfunction. Elevated neurohormonal levels are associated with increased mortality in patients with congestive heart failure. Multiple studies have shown that angiotensin-converling enzyme inhibitors decrease mortality and morbidity in these patients. In Studies of Left Ventricular Dysfunction (SOLVD), enalapril significantly reduced mortality in patients with symptomatic LV dysfunction (treatment trial). In contrast, in patients with asymptomatic LV dysfunction (prevention trial), there was no significant reduction in mortality with enalapril therapy. The effect of enalapril was examined in 333 prevention trial and 129 treatment trial patients. Plasma norepinephrine (NE) and plasma renin activity were measured in these patients at baseline, and at 4 and 12 months of follow-up. In a subset of these patients, atrial natriuretic peptide (ANP) and arginine vasopressin were also measured. Analysis of covariance models were used to determine the effect of enalapril on each neurohormone. Participants in the treatment trial had significantly higher neurohormonal levels when compared with those in the prevention trial or normal control subjects. In the treatment trial, patients taking enalapril had a greater decrease in plasma NE levels than patients taking placebo (p

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction—a randomized clinical trial in patients with left ventricular ejection fraction

Clinical and exper-imental studies implicate oxidative stress (ie, the greater produc-tion of reactive oxygen species (ROS) relative to antioxidantdefenses) as an important contributor to the pathogenesis andprogression of HF. The mechanisms underlying the deleteriouseffects of ROS in HF are multifaceted and include the ability toimpair cardiac myocyte ionic homeostasis and contractile func-tion, as well as promoting adverse cardiac remodelling.

Objectives. This study examined the relation between neurohumoral activation and severity of left ventricular dysfunction and congestive heart failure in a broad group of patients with depressed left ventricular function who were not recruited on the basis of eligibility for a therapeutic trial. Background. Previous studies have established the presence of neurohumoral activation in patients with severe congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to an impairment in left ventricular function. Methods. From the 6,273 patients recruited into the Studies of Left Ventricular Dysfunction Registry (SOLVD), a subgroup of 859 patients were randomly selected, and their plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were correlated with clinical findings, New York Heart Association functional class, left ventricular ejection fraction and drug use. Results. There was a weak but significant correlation between ejection fraction and an increase in plasma norepinephrine (rho = −0.18, p < 0.0001), plasma renin activity (rho = −0.24, p < 0.0001) and arginine vasopressin (rho = −0.12, p < 0.003). The only exception was atrial natriuretic peptide, which showed the best correlation to ejection fraction (rho = −0.37, p < 0.0001). Deterioration in functional class was associated more with increases in atrial natriuretic peptide (p = 0.0003) and plasma renin activity (p = 0.0003) and less with an increase in plasma norepinephrine. Of the clinical variables, elevated jugular venons pressure and third heart sound (S3) gallop were significantly associated with increased levels of plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. We then compared the relation of neurohormones with clinical signs, functional status, ejection fraction and drag therapy and controlled for mutual interactive effects. After adjustment, a decrease in ejection fraction was still significantly related to an increase in plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. In contrast, only a difference between functional classes I and III/IV was associated with an increase in plasma renin activity and atrial natriuretic peptide levels. Conclusions. Neurohumoral activation in patients with heart failure is related to severity of left ventricular functional depression, and this relation is independent of functional class or concomitant drug therapy.

Objectives. The aim of this study was to determine the differences in neurohumoral responses between patients with pulmonary congestion with and without impaired left ventricular ejection fraction.Background. Previous studies have established the presence of neurohumoral activation in patients with congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to the impairment in systolic contractility.Methods. The 898 patients recruited into the Studies of Left Ventricular Dysfunction (SOLVD) Registry substudy were examined to identify those patients with pulmonary congestion on chest X-ray film who had either unpaired ( 45%, group II) left ventricular ejection fraction. Plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were measured in these two groups of patients and compared with values in matched control subjects,Results. Distribution of the New York Heart Association symptom classification was the same in the two groups of patients. Compared with control subjects, patients in group II with pulmonary congestion and preserved ejection fraction had no activation of the neurohumoral mechanisms, except for a small but statistically significant increase in arginine vasopressin and plasma renin activity. Compared with patients in group II, those in group I with pulmonary congestion and unpaired ejection fraction had significant increases in plasma norepinephrine (p < 0.002), plasma renin activity (p < 0.02) and atrial natriuretic peptide levels (p < 0.0007). When we controlled for baseline differences between groups I and II, the between-group differences in plasma norepinephrine (p < 0.02) and atrial natriuretic peptide (p < 0.002) remained significant. However, plasma renin activity was not significantly different between groups I and II. When the effects of diuretic agents and angiotensinconverting enzyme inhibitors were adjusted, patients with lower ejection fraction were found to have significantly higher plasma norepinephrine and atrial natriuretic peptide levels.Conclusions. The results point to the importance of the decrease in left ventricular ejection fraction as one of the mechanisms for activation of neurohormones in patients with heart failure.

CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand.We examined the frequencies of V249I and T280M among early-onset CAD patients (G1; n = 149;50 years), late-onset CAD patients (G2; n = 150;65 years) and healthy controls (HC; n = 149, 47-93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein-C (HDL-C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non-carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI).G1 patients had non-significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL-C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related.There were significantly higher lipid ratios in G1 compared to G2 and HC (G1G2HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early-onset CAD. Neither allele affected MI or lipid levels.

Aim To determine the impact of previous coronary artery revascularization by percutaneous transluminal coronary angioplasty and/or stenting (PCI) on outcome after subsequent coronary artery bypass grafting (CABG).Methods and results The ischaemia management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial, conducted between November 1999 and September 2004, tested whether early initiation of an angiotensin-converting enzyme inhibitor post-CABG, in stable patients with LVEF >= 40%, would reduce cardiovascular events. Of the 2489 patients included in the IMAGINE trial, undergoing their first operation, 430 had a history of PCI prior to surgery (PCI group), and 2059 were referred to surgery without previous PCI (non-PCI group). There was a significant increase in the primary IMAGINE endpoint in the PCI group, HR = 1.53 [1.17-1.98], P = 0.0016. Coronary revascularization, HR = 1.80 [1.13-2.87], P = 0.014, unstable angina requiring hospitalization, HR = 2.43 [1.52-3.89], P = 0.0002, were the two individual components that significantly increased in the PCI group, even when adjusted for baseline characteristics (age, sex, history of myocardial infarction or stroke, diabetes, treatment group, or off-pump surgery).Conclusion Patients with left ventricular ejection fraction >= 40% having a history of PCI prior to surgery had a worse outcome post-CABG than those with no prior PCI. Further studies are needed to investigate whether these results apply for drug eluting stents.

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.

Body surface ST integral maps were recorded in 36 coronary artery disease (CAD) patients at: rest; peak, angina-limited exercise; and, 1 and 5 min of recovery. They were compared to maps of 15 CAD patients who exercised to fatigue, without angina, and eight normal subjects. Peak exercise heart rates were similar (NS) in all groups. With exercise angina, patients with two and three vessel CAD had significantly (p less than 0.05) greater decrease in the body surface sum of ST integral values than patients with single vessel CAD. CAD patients with exercise fatigue, in the absence of angina, had decreased ST integrals similar (NS) to patients with single vessel CAD who manifested angina and the normal control subjects. There was, however, considerable overlap among individuals; some patients with single vessel CAD had as much exercise ST integral decrease as patients with three vessel CAD. All CAD patients had persistent ST integral decreases at 5 min of recovery and there was a direct correlation of the recovery and peak exercise ST changes. Exercise ST changes correlated, as well, with quantitative CAD angiographic scores, but not with thallium perfusion scores. These data suggest exercise ST integral body surface mapping allows quantitation of myocardium at ischemic risk in patients with CAD, irrespective of the presence or absence of ischemic symptoms during exercise. A major potential application of this technique is selection of CAD therapy guided by quantitative assessment of ischemic myocardial risk.

Background— Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors. Methods and Results— The Ischemia Management with Accupril post–bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (≤7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40%. The trial was a double-blind, placebo-controlled study of 2553 patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years. The incidence of the primary composite end point (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P =0.212) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P =0.0356). Adverse events also increased in the quinapril group, particularly during the first 3 months after CABG. Conclusions— In patients at low risk of cardiovascular events after CABG, routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG; however, it increases the incidence of adverse events, particularly early after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk.

Between 1984 and 1993, prevalence and case fatality of hospitalized acute myocardial infarction (AMI) had declined in the population of Halifax County. We aimed to determine whether these trends continued into the 21st century by investigating patient characteristics, treatment methods, and fatality for hospital admissions of residents of Halifax County, aged 25-74, during 1984-1989 (period 1), 1990-1993 (period 2), and 1998-2001 (period 3) and diagnosed as AMI that were extracted from databases for the Halifax County MONICA and ICONS (Improving Cardiovascular Outcomes in Nova Scotia) Studies. Trends in patient characteristics and treatment methods were assessed by chi2 statistics. Their association with 28-day fatality was determined by logistic regression. Event rate declined during 1984-1993 but not into 1998-2001 (p = 0.206). Compared with 1990-1993, fewer AMI patients during 1998-2001 wereor = 55 years (73.3% vs. 69.9%), cigarette smokers (49.8% vs. 42.9%), had a history of myocardial infarction (28.9% vs. 24.9%), and had an admission heart rate100 (34.8% vs. 17.4%). Additionally, more patients had a history of diabetes (22.5% vs. 28.1%). Case fatality declined progressively over the 3 study time periods (16.6%, 13.1%, and 9.4%, respectively). Changes also occurred in prevalence of Killip class 4 status during admission (20.2%, 10.3%, and 13.3%, respectively), use of thrombolysis (9.0%, 30.9, and 32.6%, respectively), and percutaneous coronary intervention (PCI) (4.3%, 11.2%, and 22.4%, respectively) in the different periods. Significant associations were found between case fatality and patient history of diabetes, history of MI, age, elevated admission heart rate, Killip class 4 impairment, thrombolysis, and PCI. The ICONS registry of hospitalized acute myocardial infarctions was used to compare case fatality during 1998-2001 with that reported by the Halifax County MONICA Project for 1984-1993. Whereas the population rate of myocardial infarctions had declined between 1984-1993 but not subsequently, case fatality declined significantly throughout the study period. The continued decline in case fatality is likely explained by changes in patient profile on presentation and medical therapies, including the increased use of thrombolysis and PCI.

The prognostic significance of left ventricular hypertrophy (LVH) identified by simple electrocardiographic (ECG) criteria in high-risk patients with established cardiovascular (CV) diseases is not clearly understood.The Heart Outcomes Prevention Evaluation (HOPE) trial was a randomized trial, which evaluated the effects of ramipril and of vitamin E on major CV outcomes in 9541 men and women aged 55 years or older with a history of coronary artery disease, stroke, peripheral vascular disease or diabetes mellitus with at least one additional CV risk factor. Patients were followed for an average of 4.5 years. We evaluated the association between simple ECG criteria for LVH and the risk for major vascular events, for CV and all-cause mortality and for heart failure.Electrocardiographic LVH was present in 793 (8.3%) HOPE study participants. Of these, 19.0% sustained a major CV event (MI, stroke or CV death), 15.6% died and 6.1% developed heart failure compared with 15.6%, 10.8% and 2.9% respectively of those without ECG-LVH (P = 0.0023; P0.0001 and P0.0001). In multivariate analysis ECG-LVH was an independent predictor of CV and all-cause death and of heart failure.In patients with CV disease simple, easily applicable ECG criteria for LVH identify a subset of individuals at particularly high risk for death and for heart failure.

Medical, social and economic costs of congestive heart failure (CHF) continue to rise. There exists a 'care gap' between what the optimal care populations with CHF should receive and actually do receive. Central to the goal to develop effective strategies against the 'care gap' is accurate measurement of the CHF burden. Administrative data are limited in detail and accuracy and clinical databases suffer from limited size. Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a province-wide population-based disease management study with access to all patient health data including outcomes.Medical records of all patients admitted to any Nova Scotia health care institution with a cardiovascular disorder were prospectively examined by trained abstractors. Patients were followed up and health outcomes measured through assignment of unique identifier numbers and linkage with Vital Statistics Nova Scotia. This report summarizes baseline data for the population admitted to hospital with a diagnosis of CHF between October 15, 1997 and October 14, 1998.There were 2637 unique patients enrolled with 3547 hospitalizations. The median length of stay was eight days, with in-hospital mortality of 18.2%; 10.8% were discharged to long term care. The mortality rate was 38.7% at 12 months and the rehospitalization rate was 39.9%. Average age was 75 +/- 10 years (median 76) and 52% were female. There were 4.5 comorbidities per patient. Left ventricular ejection fraction (LVEF) was measured in fewer than 40%; of these, fewer than 39% had a documented ejection fraction less than 40%. At discharge, 61.3% of survivors were prescribed angiotensin-converting enzyme (ACE) inhibitors, 6.0% angiotensin blockers, 42.1% beta-blockers, 75.6% diuretics, 26.1% calcium channel blockers and 19.3% warfarin. Females were older and had lower rate of LVEF testing and ACE and warfarin usage.The burden of disease for CHF in Nova Scotia is large and affects an elderly population with multiple comorbidities. Adverse outcomes such as death, rehospitalization and admission to a chronic care facility are common. Measurement of the 'care gap' requires consideration of these factors and of elderly and female patients regardless of left ventricular function. Successful strategies will likely be multidisciplinary in scope with a focus toward improving access to care.

Purpose Poor documentation in medical records might reduce the quality of care and undermine analyses based on retrospective chart reviews. We assessed the documentation of cardiac risk factors and cardiac history in the records of patients hospitalized with myocardial infarction or heart failure. Methods We performed a retrospective cohort study involving direct chart audit of all consecutive hospitalizations for myocardial infarction (n = 2109) or heart failure (n = 3392) in Nova Scotia, Canada, from October 15, 1997, to October 14, 1998. The main outcome measures were the documentation rates for prespecified clinical items, including cardiac risk factors and history of myocardial infarction or heart failure, which were recognized as indicators of the quality of care for the conditions under study. Results Information was not documented in a high proportion of cases, ranging from 9% (smoking) to 58% (previous history of heart failure) in charts from patients hospitalized for myocardial infarction, and from 19% (smoking) to 69% (hyperlipidemia) in charts from heart failure hospitalizations. Lack of documentation was more common in women and the elderly. Conclusion Documentation of important clinical information is poor even in the hospital charts of patients with severe conditions. This quality-of-care issue has implications for health services and outcomes research, including the development of report cards.

Background The Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) gene has been associated with coronary artery disease (CAD) in some but not all studies. To determine the impact of the mutant Asp298 eNOS allele on the development of premature CAD, we examined the prevalence of this mutation in patients with early-onset CAD compared with those manifesting CAD later in life. If this mutation confers an increased risk of premature CAD, we hypothesized that the frequency of the homozygous mutation (Asp298Asp298) would be greater among the younger patient group. Methods A total of 299 patients with a history of myocardial infarction (MI) or angina pectoris plus angiographically documented CAD were studied. Patients were divided into 2 groups: group 1 (149 patients) included patients with CAD before the age of 50 years and group 2 (150 patients) included patients with a first presentation of CAD at >65 years old. Prevalence of eNOS Glu298 and Asp298 alleles was assessed by molecular analysis and compared for the 2 groups. Results There was no significant difference in the frequency of the mutant Asp298 allele between the 2 groups (G1: 42% vs G2: 42.7%, P =.79). The frequencies of the Glu298Glu298, Glu298Asp298, and Asp298Asp298 genotypes were similar in both groups (34.9%, 46.3%, and 18.8% for G1 and 29.3%, 56%, and 14.7% for G2, respectively, P =.29). Conclusions Our study does not support the conclusion that the eNOS Asp298 allele contributes to the development of premature CAD. (Am Heart J 2001;142:586-9.)

Background The Queen Elizabeth II Health Sciences Centre uses a weekly peer-review conference of cardiovascular experts to prioritize each surgical case to 1 of 4 queues with the use of standardized criteria of coronary anatomy, stress test result, and symptoms. We examined the hazard of waiting as well as the impact of waiting on surgical outcomes. Methods and Results Analysis was performed for 2102 consecutive patients queued for CABG, aortic valve replacement, or CABG+aortic valve replacement between January 1, 1998, and December 31, 1999. Among 1854 patients undergoing surgery, median waiting times on the respective queues were as follows: in-house urgent group, 8 days; semiurgent A group, 37 days; semiurgent B group, 64 days; and elective group, 113 days. There were 13 deaths (12 cardiac) that occurred during the waiting period (0.7% of the patients). Of the 8.7% patients upgraded to a more urgent queue, 86.1% required hospitalization before surgery. Although female sex was not associated with prolonged waiting time, it was predictive of urgent status ( P =0.001). The incidence of postoperative complications was 25.0%, and operative mortality was 2.86%. Both were more frequent among patients undergoing surgery early ( P =0.01); however, this difference was attributable to the in-house urgent queue. The median length of stay was 7 days for all patients and was not affected by waiting time. Conclusions Death and upgrades while the patients were waiting tended to occur early in the queuing process, and prolonged waiting was not associated with worse surgical outcomes. The cost of reducing waiting times could in part be offset by prevention of hospital admissions among upgraded patients.

Objective: Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. Methods: 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. Results and Conclusions: None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10–0.73.

Objective: In the presence of low serum folate, mutant 5,10-methylenetetrahydrofolate reductase (MTHFR+ [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. Methods: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. Results: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). Conclusion: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

OBJECTIVES: To explore psychological and socioeconomic concerns of patients who queued for coronary artery bypass surgery and the effectiveness of support existing in one Canadian cardiovascular surgical center. DESIGN: Standardised questionnaire and structured interview. SETTING: Victoria General Hospital, Halifax, Nova Scotia. SUBJECTS: 100 consecutive patients awaiting non-emergency bypass surgery. RESULTS: Most patients (96%) found the explanation of findings at cardiac catheterisation and the justification given for surgery satisfactory. However, 84 patients complained that waiting for surgery was stressful and 64 registered at least moderate anxiety. Anger over delays was expressed by 16%, but only 4% thought that queuing according to medical need was unfair. Economic hardship, attributed to delayed surgery, was declared by 15 patients. This primarily affected those still working--namely, blue collar workers and younger age groups. Only 41% of patients were satisfied with existing institutional supports. Problems related mainly to poor communication. CONCLUSIONS: Considerable anxiety seems to be experienced by most patients awaiting bypass surgery. Better communication and education might alleviate some of this anxiety. Economic hardship affects certain patient subgroups more than others and may need to be weighed in the selection process. A more definitive examination of these issues is warranted.

Unilateral Stellate Block. Introduction: Left sided stellate ganglion predominance has been proposed as a mechanism responsible for lethal ventricular arrhythmias, due to hetaerae nouns ventricular repolarization. To determine the cardiovascular effects of such asymmetric sympathetic ganglion innervations in man, studies were performed in 15 patients undergoing unilateral stellate ganglion blockade for the management of chronic arm pain. Methods and Results: Standard 12-lead ECGs, systemic blood pressure, body surface potential mapping, and radionuclide angiography were performed during rest and graded exercise before and after blockade. Successful unilateral blockade was accomplished in 13 of the patients, 11 of whom had right-sided blockade and two left-sided blockade. No significant changes due to blockade of stellate ganglia, including QT intervals, were detected during rest or graded exercise in standard ECGs. No cardiac rhythm disturbances occurred in these states, Body surface potential maps and arterial blood pressure were similar during resting supine and upright positions, as well as immediately after exercise before and after blockade. Unilateral ganglion blockade did not modify resting or exercise cardiac ejection fractions. Conclusion: Unilateral stellate blockade in man does not induce untoward cardiovascular effects during rest or exercise.

A total of 6,273 consecutive relatively unselected patients with heart failure or left ventricular dysfunction, or both (mean age 62 ± 12 years, mean ejection fraction 31 ± 9%), were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry over a period of 14 months. All patients were followed up for vital status and hospital admissions at 1 year. Ischemic heart disease was the underlying cause of failure or dysfunction in ≈70% of patients, whereas hypertensive heart disease was considered to be primarily involved in only 7%. There were striking differences in the etiology of heart failure among blacks and whites: 73% of whites had an ischemic etiology of failure versus only 36% of blacks; 32% of blacks had a hypertensive condition versus only 4% of whites. The total 1-year mortality rate was 18%; 19% of patients had hospital admissions for heart failure and 27% either died or had a hospital admission for congestive heart failure during the 1st year of follow-up. Factors related to 1-year mortality or hospital admission for congestive heart failure included age, ejection fraction, diabetes mellitus, atrial fibrillation and female gender. There was no difference in mortality associated with congestive heart failure among blacks and whites, but hospital admissions for heart failure were more frequent in blacks. Digitalis and diuretic agents were the drugs most often used in these patients, who were often making many medications in relation to severity of congestive heart failure symptoms and ejection fraction. Surprisingly, angiotensin-converting enzyme inhibitors were taken by only 30% of patients, and a substantial number were treated by drugs controversial in the presence of left ventricular dysfunction and heart failure, such as calcium channel antagonists and antiarrhythmic or beta-adrenergic blocking agents.

The effects of increasing heart rate by six different methods on cardiac function were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atrioventricular sequential pacing, (5) right stellate ganglion stimulation, and (6) isoproterenol administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary blood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricular sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.

The Canadian Cardiovascular Society (CCS) classification of angina pectoris has been widely adopted since its introduction in the 1970s. Recent appraisals of this classification scheme have identified a number of concerns, including (1) the unproven assumption of symptomatic or physiologic equivalence among diverse levels of different activities within individual angina grades, (2) the fact that the scale is potentially cumbersome were one to work through the full permutations of symptoms and qualifiers for each patient, and (3) the weak relation between symptom severity as captured by the scale and anatomic disease or prognosis. To high-light patients' perceptions of their own functional limitations and to assess how such introspection has compared with the categorization accorded by medical personnel using the CCS scale, we developed a patient disability score, a 4-grade scale that simply refers to “no”, “mild”, “moderate”, or “severe limitation of desired activities”.