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Background: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease.Objective: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients.Design: Subset analysis of a randomized, controlled trial.Setting: 80 hospitals and affiliates in the United States and Canada.Patients: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL).Intervention: Pravastatin, 40 mg/d, or placebo.Measurements: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke.Results: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P < 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [CI, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [CI, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (CI, 8 to 24) to prevent a major coronary event and 22 (CI, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients.Conclusions: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial. [ABSTRACT FROM AUTHOR]

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, AMPK Tyr172 /ACC Ser79 signalling and the acetylation of ß-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., (© 2019 John Wiley & Sons Ltd.)

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., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

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., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: 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., Objectives: To determine the effectiveness of HF clinics in reducing death or all-cause rehospitalization in a real-world population., Methods: 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., Results: 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], P<0.0001; NNT=4), and combined mortality or hospital readmission (HR 0.73 [95% CI 0.60 to 0.89], P<0.0015; NNT=5)., Discussion: 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.

Objectives: 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., Material and Methods: 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)., Results: 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 (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related., Conclusions: There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), 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.

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.

Objectives: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C]., Design and Methods: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes., Results: Early-onset CAD patients had increased, but non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C (P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls (P = 0.03). There were significantly more APOE epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44-5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%., Conclusions: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate 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 were > or = 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.

Heart failure remains a common diagnosis, especially in older individuals. It continues to be associated with significant morbidity and mortality, but major advances in both diagnosis and management have occurred and will continue to improve symptoms and other outcomes in patients. The Canadian Cardiovascular Society published its first consensus conference recommendations on the diagnosis and management of heart failure in 1994, followed by two brief updates, and reconvened this consensus conference to provide a comprehensive review of current knowledge and management strategies. New clinical trial evidence and meta-analyses were critically reviewed by a multidisciplinary primary panel who developed both recommendations and practical tips, which were reviewed by a secondary panel. The resulting document is intended to provide practical advice for specialists, family physicians, nurses, pharmacists and others who are involved in the care of heart failure patients. Management of heart failure begins with an accurate diagnosis, and requires rational combination drug therapy, individualization of care for each patient (based on their symptoms, clinical presentation and disease severity), appropriate mechanical interventions including revascularization and devices, collaborative efforts among health care professionals, and education and cooperation of the patient and their immediate caregivers. The goal is to translate best evidence-based therapies into clinical practice with a measureable impact on the health of heart failure patients in Canada.

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: 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., Methods: 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., Results: 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., Conclusion: 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.

Background: Previous reports have suggested that internists employ evidence-based care for congestive heart failure (CHF) less frequently than cardiologists. Reasons for this possible difference are unclear., Methods: A retrospective review of 185 consecutive patients admitted to a Canadian tertiary care facility between April 1998 and March 1999 with a primary diagnosis of CHF and who were treated by internists (IM group) or cardiologists (CARD group) was conducted., Results: The CARD group (n=65) was younger (70 versus 76 years, P<0.001) and had larger left ventricular end-diastolic diameter by echocardiography (57 versus 51 mm, P=0.006) than the IM group (n=120). The CARD group documented ejection fraction in 90% of cases versus 54% in the IM group (P<0.05). There was no difference in angiotensin-converting enzyme (ACE) inhibitor usage (68% versus 63%, P=0.48) or optimal ACE dosage (CARD 50% versus IM 42%, P=0.44). Multivariate predictors of ACE inhibitor usage were serum creatinine, male sex, peripheral edema and increasing serum glucose. The CARD group had higher usage of beta-blockers (69% versus 49%, P<0.009), lipid lowering medication (35% versus 17%, P<0.004) and warfarin therapy for atrial fibrillation (74% versus 28%, P<0.005)., Conclusion: The data suggest that Canadian cardiologists and internists use ACE inhibitors equally and care for a relatively similar group of CHF patients. However, beta-blockade, warfarin, lipid lowering therapy and documentation of critical data occurred more frequently under cardiologist care. The possibility that there may be a gradation of adoption of newer guidelines for CHF care according to physician specialty is raised.

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 = 2,109) or heart failure (n = 3,392) 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.

Objectives: 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., Design and Methods: 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., Results: 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., Conclusions: 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.

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.

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.

Background: Septal systolic motion is determined by the end-diastolic trans-septal pressure gradient, and hence is load dependent., Objective: To explore septal contribution to left ventricular (LV) systolic function in patients with heart failure., Design: Echocardiograms were identified post hoc from normal subjects and a cohort of patients with heart failure., Patients: Twelve normal subjects and 69 patients with heart failure and normal conduction or left bundle brance block (LBBB) were studied., Methods: Parasternal short axis LV end-diastolic and end-systolic areas were traced. Using a floating centroid, 32 radial chords were constructed, and perecentage shortening from end-diastole to end-systole was calculated for each chord., Main Results: Comparing heart failure with normal conduction and LBBB, LV end-diastolic area was similar (43+/-10 versus 45+/-12 cm(2) not significant), but stroke area was higher in normal conduction (7+/-4 versus 4+/-4cm(2), P<0.05) as was area ejection fraction (0.17+/-0.11 versus 0.10+/- 0.08, P<0.01). In normal subjects, the summed percentage shortening of 10 midseptal chords was similar to that of 10 midfreewall chords (256+/-16% versus 235+/-32%, not significant). In contrast, patients with heart failure and normal conduction had greater midseptal than midfreewall sum med chord shortening (113+/-18% versus 60+/-12%, P<0.05); patients with heart failure and LBBB had paradoxical septal motion (3+/-28, P<0.05 compared with normal conduction)., Conclusions: Patients with heart failure and normal conduction have an enhanced septal contribution to LV systolic function compared with normal subjects. In heart failure with LBBB, this is lost and the area ejection fraction is lower. Strategies to optimize septal function in heart failure warrant further study.

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 5,20-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.

Objective: To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis., Background: Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously., Methods: Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically., Results: There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females., Conclusions: Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in 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.

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 < or = 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 > or = 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 < or = 1 week in 25%, < or = 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., Conclusion: 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.

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-converting 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 < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Many of the recommendations presented in this consensus report are summarized in Figure 2. All patients with known or suspected heart failure should undergo a detailed history and physical examination. Other causes for the symptoms and/or clinical signs indicative of heart failure should be excluded. Routine biochemical tests, as well as a standard chest x-ray and ECG, should be performed on all patients with heart failure. Precipitating or aggravating causes of heart failure should be eliminated. Patients with potentially surgically correctable lesions, such as constrictive pericarditis, valvular disease or left ventricular aneurysm, should be referred for cardiological evaluation and the appropriate surgery. Patients with ischemic induced heart failure should be assessed for possible revascularization by either angioplasty or bypass surgery. Pending clinical findings and the degree of systolic or diastolic dysfunction present, determined by noninvasive tests, the panel made recommendations concerning the choice of various therapeutic agents. These clinical guidelines have been developed for practising physicians who manage patients with heart failure. The process by which consensus recommendations were developed by the Canadian Cardiovascular Society was based on the principle that guidelines have the best chance of succeeding if they are developed by those who will be using them. Strategies that ensure physicians are aware of the current guidelines, and that their implementation leads to measurable improvement in the diagnosis and management of patients with heart failure must be developed. Consensus reports represent an ongoing process which is subject to revision when further conclusive evidence is obtained by ongoing and future clinical trials.

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 venous 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 drug 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: This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo., Background: Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure., Methods: A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction < or = 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560)., Results: Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire., Conclusions: Modest benefits in quality of life for > or = 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.

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 impaired (< or = 45%, group I) or preserved (> 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 impaired 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 angiotensin-converting 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.

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 approximately 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 taking many medications in relation to severity of congestive heart failure symptoms and ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction: Left-sided stellate ganglion predominance has been proposed as a mechanism responsible for lethal ventricular arrhythmias, due to heterogenous ventricular repolarization. To determine the cardiovascular effects of such asymmetric sympathetic ganglion innervation 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 ganglionic 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.

Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.

Objective: To investigate whether desensitization of inotropic responses elicited during prolonged efferent sympathetic neural stimulation is due to decreased responsiveness of myocardial beta-adrenergic receptors or to alterations in the efferent sympathetic neurons innervating the heart., Design: Increasing doses of noradrenaline and isoproterenol were administered intravenously before and during prolonged (20 mins) stimulation of the intrathoracic efferent sympathetic nervous system of eight dogs. Cardiac augmentor responses were correlated with liberation of catecholamines by the heart. In a second group of experiments (nine dogs), right and left ventricular beta-adrenergic receptor number and affinity were determined before and during such stimulations., Main Results: Similar ventricular augmentations were induced when isoproterenol or noradrenaline was administered before and after 20 mins of efferent sympathetic neural stimulation. During the early peak stimulation response, no further augmentations were induced by isoproterenol or noradrenaline. Liberation of noradrenaline by the heart followed a similar course after an initial peak, while noradrenaline values fell to levels which were 6% of those attained during peak response after 20 mins of continuous stimulation. The Bmax and Kd of ventricular beta-adrenergic receptors were similar before and after 20 mins of efferent sympathetic neural stimulation., Conclusions: Desensitization of ventricular inotropism that occurs during prolonged cardiac efferent sympathetic nervous system stimulation is not primarily due to alteration of myocyte cell surface beta-adrenergic receptors or to a change in myocyte responsiveness to beta-adrenergic agonists, but rather to a reduction in noradrenaline release by sympathetic efferent post ganglionic neurons presumably reflecting a reduction in the activity of these neurons despite continued stimulation.

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.

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.

We studied the evolution of body-surface potential map (BSPM) patterns in 32 patients following first acute inferior myocardial infarction. Initial BSPMs were obtained at a mean of 79 hours post-infarction; follow-up BSPMs, a mean of eight months post-infarction. Temporal area-of-difference maps, constructed by subtracting initial from follow-up group-mean BSPMs, revealed reciprocal changes over the superior and inferior torso for both Q-zone and ST-segment time-integral distributions. The temporal changes in Q-zone patterns were small but definite: over the inferior torso there was a relative gain in Q-zone values and, over the superior torso, a relative decrease. In contrast, there were marked spatial and quantitative changes of ST-segment distributions during the follow-up period. Over the superior torso, particularly anteriorly, there was a gain in ST-segment values; over the inferior torso, a decrease. With the small temporal changes in Q-zone time-integral distributions, individual Q-zone maps continued to reflect a pattern of inferior myocardial infarction at follow-up. In contrast, the marked temporal changes in ST-segment time-integral distributions resulted in individual map patterns at follow-up that were nearly indistinguishable from normal ST-segment maps. The relatively small changes in depolarization time-integral patterns during the early post-infarction period suggest that the Q-zone patterns of the acute phase of myocardial infarction reflect near-irreversible or completed myocardial damage. The marked normalization of repolarization time-integral patterns during the recovery phase suggests, however, that there are also considerable areas of myocardium-at-risk during the early phase of the infarction process which stabilize with time.