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The Antarctic environment presents an extreme variation in the natural light-dark cycle which can cause variability in the alignment of the circadian pacemaker with the timing of sleep, causing sleep disruption, and impaired mood and performance. This study assessed the incidence of circadian misalignment and the consequences for sleep, cognition, and psychological health in 51 over-wintering Antarctic expeditioners (45.6 ± 11.9 years) who completed daily sleep diaries, and monthly performance tests and psychological health questionnaires for 6 months. Circadian phase was assessed via monthly 48-h urine collections to assess the 6-sulphatoxymelatonin (aMT6s) rhythm. Although the average individual sleep duration was 7.2 ± 0.8 h, there was substantial sleep deficiency with 41.4% of sleep episodes7 h and 19.1%6 h. Circadian phase was highly variable and 34/50 expeditioners had sleep episodes that occurred at an abnormal circadian phase (acrophase outside of the sleep episode), accounting for 18.8% (295/1565) of sleep episodes. Expeditioners slept significantly less when misaligned (6.1 ± 1.3 h), compared with when aligned (7.3 ± 1.0 h; p .0001). Performance and mood were worse when awake closer to the aMT6s peak and with increased time awake (all p .0005). This research highlights the high incidence of circadian misalignment in Antarctic over-wintering expeditioners. Similar incidence has been observed in long-duration space flight, reinforcing the fidelity of Antarctica as a space analog. Circadian misalignment has considerable safety implications, and potentially longer term health risks for other circadian-controlled physiological systems. This increased risk highlights the need for preventative interventions, such as proactively planned lighting solutions, to ensure circadian alignment during long-duration Antarctic and space missions.

New Zealand has among the highest rates of colorectal cancer and inflammatory bowel disease in the world. With the imminent rollout of the National Bowel Screening Programme, we sought to determine the capacity of and demand faced by the current gastroenterology specialist workforce, and to compare it with other countries.Specialists in gastroenterology were asked to complete a questionnaire on their education, number of FTE in the public and private sectors, number of colonoscopies performed, anticipated years to retirement and other associated information. Additional statistics were obtained from personal communication, visits to endoscopy units throughout the country and government datasets.In November 2017 there were 93 gastroenterologists in New Zealand, equating to 1.96 gastroenterologist specialists/100,000 population. The response rate was 55%. One quarter of gastroenterologists spent time working in general internal medicine additionally to gastroenterology in public hospitals. Fifty-one percent of gastroenterologists were older than 50 years and 42% aimed to retire within the next 10 years. Four of the 20 district health boards had no gastroenterologists in post.New Zealand has a lower specialist gastroenterologist ratio and older workforce compared with other comparable western countries and may struggle to meet the growing gastroenterology healthcare needs of the population. Substantial regional gastroenterology service inequities exist across the country.

Endoscopic variceal ligation (EVL) is an important treatment modality in managing complications of portal hypertension. Since its advent 30 years ago, the procedural complications have decreased significantly, especially when compared with variceal sclerotherapy. With the current widespread use of EVL, rare complications are now becoming increasingly recognized. We present a case of complete esophageal obstruction, its management, and clinical course. Our literature review identified only eight reported cases. We compare the varied treatment approaches and outcomes in the cited articles.

Background— The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results— We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P P =0.001), and improved net clinical benefit (adjusted P P =0.082 for ischemic stroke and adjusted P =0.109 for major hemorrhage). Conclusions— In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00041938.

Background Conflicting data exist regarding the association between left ventricular (LV) lead position and benefit from cardiac resynchronization therapy. We evaluated the relationships between LV lead positions and the risk of death or hospitalization for heart failure (HF) in the cardiac resynchronization therapy arm of the R esynchronization-Defibrillation for A mbulatory Heart F ailure T rial (RAFT). Methods LV lead position was categorized by site investigator (MD) and in a chest radiograph core laboratory (CXR) as "anterior," "lateral," or "posterior" in the short axis, and "basal," "mid," or "apical" in the long axis. Agreement between MD and CXR LV lead position classification was evaluated and the independent relationship between LV lead position and clinical outcome was assessed using Cox multivariable models. Results Agreement between MD and CXR LV lead position was poor (κ ≤ 0.26). Over 39 ± 20 months, 140 of 447 (31.3%) patients met the RAFT primary end point (death or HF hospitalization). In adjusted analyses, neither MD-determined nor CXR-determined anterior or apical LV lead position was significantly associated with the primary outcome. However, CXR-defined apical LV lead position was associated with a higher risk of HF hospitalization (hazard ratio, 1.99; P = 0.004). Conclusions Poor agreement between implanting physician and core lab CXR-based categorizations of LV lead position was observed. Neither categorization method resulted in significant associations between apical or anterior LV lead position and the risk of the composite primary outcome of death or heart failure hospitalization. However, CXR-defined apical lead position was associated with increased risk of HF hospitalization.

Purpose of review This paper reviews the effect of cardiac resynchronization therapy (CRT) on patients with heart failure symptoms, in particular, in patients with mild symptoms of heart failure. It provides the rationale and design of a randomized controlled trial to determine if CRT, when added to implantable cardioverter defibrillator, will be beneficial in patients with left ventricular dysfunction, ventricular conduction delay and mild heart failure symptoms. Recent findings CRT has been demonstrated to improve functional capacity, quality of life, and reduce heart failure hospitalization in patients with advanced symptomatic heart failure, and evidence of a ventricular conduction abnormality on ECG. In patients with milder heart failure symptoms, three randomized controlled trials and observational studies failed to convincingly show improvement of functional status, but demonstrated improved ventricular reverse remodelling with more advanced heart failure patients. Summary Two large randomized clinical trials are currently ongoing (RAFT and MADIT-CRT). The results of these trials will determine the efficacy of CRT in patients with systolic heart failure, ventricular conduction abnormality and milder symptoms.

Background— Higher levels of red blood cell distribution width (RDW) may be associated with adverse outcomes in patients with heart failure. We examined the association between RDW and the risk of all-cause mortality and adverse cardiovascular outcomes in a population of people with coronary disease who were free of heart failure at baseline. Methods and Results— We performed a post hoc analysis of data from the Cholesterol and Recurrent Events study. Baseline RDW was measured in 4111 participants who were randomized to receive pravastatin 40 mg daily or placebo and followed for a median of 59.7 months. We used Cox proportional hazards models to examine the association between RDW and adverse clinical outcomes. During nearly 60 months of follow-up, 376 participants died. A significant association was noted between baseline RDW level and the adjusted risk of all-cause mortality (hazard ratio per percent increase in RDW, 1.14; 95% confidence interval, 1.05 to 1.24). After categorization based on quartile of baseline RDW and further adjustment for hematocrit and other cardiovascular risk factors, a graded independent relation between RDW and death was observed ( P for trend=0.001). For instance, participants with RDW in the highest quartile had an adjusted hazard ratio for death of 1.78 (95% confidence interval, 1.28 to 2.47) compared with those in the lowest quartile. Higher levels of RDW were also associated with increased risk of coronary death/nonfatal myocardial infarction, new symptomatic heart failure, and stroke. Conclusions— We found a graded independent relation between higher levels of RDW and the risk of death and cardiovascular events in people with prior myocardial infarction but no symptomatic heart failure at baseline.

Background: Central obesity, diabetes mellitus, dyslipidaemia and chronic hypertension-features of the metabolic syndrome-have been individually associated with venous thromboembolism (VTE). However, whether each of these factors additively increases the risk of VTE is uncertain. Aim: To determine whether features of the metabolic syndrome independently increase the risk of VTE. Design: Prospective cohort study derived from the Heart Outcomes Prevention Evaluation 2 (HOPE-2) randomized clinical trial. Setting: One hundred and forty-five clinical centres in 13 countries. Methods: We studied 5522 adults aged >55 years with cardiovascular disease or diabetes mellitus. At enrolment, 35% had 0-1 features of the metabolic syndrome, 30% had two, 24% had three and 11% had four. We defined symptomatic VTE as an objectively confirmed new episode of deep-vein thrombosis or pulmonary embolism. Results: VTE occurred in 88 individuals during a median 5.0 years of follow-up. The incidence rate of VTE (per 100 person-years) was 0.30 with 0-1 features, 0.36 with two features, 0.38 with three features and 0.40 with four features of the metabolic syndrome (trend p=0.43). Relative to the presence of 0-1 features of the metabolic syndrome, the adjusted hazard ratio (95%Cl) for VTE was 1.22 (0.71-2.08) with two features, 1.25 (0.70-2.24) with three features, and 1.26 (0.59-2.69) with four features. Discussion: The number of features of the metabolic syndrome present was not a clinically important risk factor for VTE in older adults with vascular arterial disease.

Objective To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults. Options and Outcomes For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome. Evidence A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. Recommendations Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65mmol/day to 100mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5kg/m2 to 24.9kg/m2) and waist circumference (less than 102cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. Validation All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Background— Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling and heart failure. Despite incomplete understanding of how this process is regulated, the upregulation of tumor necrosis factor (TNF)-α after aortic banding in the myocardium is known. In the present study, we tested our hypothesis that TNF-α regulates the cardiac inflammatory response, extracellular matrix homeostasis, and ventricular hypertrophy in response to mechanical overload and contributes to ventricular dysfunction. Methods and Results— C57/BL wild-type mice and TNF-knockout (TNF −/− ) mice underwent descending aortic banding or sham operation. Compared with sham-operated mice, wild-type mice with aortic banding showed a significant increase in cardiac TNF-α levels, which coincided with myocyte apoptosis, inflammatory response, and cardiac hypertrophy in week 2 and a significant elevation in matrix metalloproteinase-9 activity and impaired cardiac function in weeks 2 and 6. Compared with wild-type mice with aortic banding, TNF −/− mice with aortic banding showed attenuated cardiac apoptosis, hypertrophy, inflammatory response, and reparative fibrosis. These mice also showed reduced cardiac matrix metalloproteinase-9 activity and improved cardiac function. Conclusions— Findings from the present study have suggested that TNF-α contributes to adverse left ventricular remodeling during pressure overload through regulation of cardiac repair and remodeling, leading to ventricular dysfunction.

Matrix metalloproteinases (MMPs) can alter myocardial extracellular matrix and thereby contribute to adverse ventricular remodeling in progressive heart failure (HF). We hypothesized that increased plasma MMP levels correlate with increased left ventricular (LV) volumes and reduced LV ejection fraction (LVEF) in patients with HF.In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, patients with symptomatic HF and LVEF0.40 were randomized to receive various combinations of therapies with candesartan, enalapril, and metoprolol CR. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and LVEF were determined by radionuclide angiography at baseline and at Week 43. Baseline and Week 43 plasma MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in 184 patients in this substudy. At baseline, plasma MMP-9 correlated positively with ESV (Spearman's rank correlation coefficient rho = 0.17, P = .02) and negatively with LVEF (rho = -0.18, P = .01). After 43 weeks, LVEF, EDV, and ESV increased significantly (all P.01); MMP-2 level increased (P = .01), but MMP-9 and TIMP-1 levels did not change significantly overall in the study population. Temporal changes in MMP-9 level were inversely correlated with changes in LVEF (rho = -0.16, P = .04). In multivariable analysis adjusting for clinical characteristics and treatment, a smaller proportional change in MMP-9 level after 43 weeks (below versus above median) predicted a concurrent improvement in LVEF (odds ratio = 2.35, 95% CI 1.24-4.46; P.01). Similar relationships for MMP-2 and TIMP-1 were not observed.Elevated plasma MMP-9 levels correlated with lower LVEF and higher ESV, whereas increasing MMP-9 levels are associated with a concurrent deterioration of LV function. These findings suggest that monitoring of plasma markers of myocardial matrix remodeling may provide important prognostic information with respect to ongoing adverse LV remodeling in HF patients.

The time course and differential effects of statin regimens on endothelial function after acute coronary syndromes (ACSs) are unknown and could contribute to the superiority of a more intense strategy. A subset of subjects who were enrolled in the PROVE IT-TIMI 22 trial (n = 50) underwent evaluation of vascular reactivity by high-resolution brachial ultrasound. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilation (NMD) were measured at baseline and at 48 hours, 1 month, and 4 months after the initiation of 40 mg of pravastatin (n = 26) or 80 mg of atorvastatin (n = 24). After 4 months, low-density lipoprotein cholesterol was decreased by 32% in the atorvastatin group but was not different from baseline after ACS in the pravastatin group. C-reactive protein decreased similarly in the 2 groups. Brachial artery diameters at rest were similar in the 2 groups and at each time point of the trial. FMD and NMD increased significantly after 4 months by 27% and 24%, respectively (p

Left ventricular (LV) and right ventricular (RV) function are known predictors of morbidity and mortality after an acute myocardial infarction (MI). However, the prognostic use of a late evaluation of cardiac function after an MI remains unclear.We analyzed echocardiograms obtained 1 year after MI in patients with LV dysfunction at baseline (ejection fraction [EF]or = 40%) from 291 patients enrolled in the SAVE echocardiographic substudy who did not develop heart failure (HF) or a recurrent MI during this first year. Left ventricular EF and RV fractional area change were assessed.After a median follow-up of 22 months after the 1-year echocardiogram, a low LVEF (30%) at 1 year was associated with an increased risk of death and/or HF (hazards ratio [HR] 2.7, 95% CI 1.3-5.3). Presence of RV dysfunction was also associated with an increased risk of death (HR 8.9, 95% CI 3.5-22.1), development of HF (HR 7.1, 95% CI 3.4-15.0), and the composite end point of death or HF (HR 7.6, 95% CI 4.1-14.2). In multivariate analyses, both low LVEF and RV dysfunction remained independently predictive of the composite end point of death or HF. Patients with biventricular dysfunction were at the greatest risk of death and/or HF (HR 19.4, 95% CI 8.2-46.0) in follow-up.In a stable population of survivors of MI, impaired LV and RV function at 1 year after MI are independently and additively predictive of increased risk of HF or death.

Grapefruit can augment oral medication bioavailability through irreversible (mechanism‐based) inhibition of intestinal CYP3A4. Supplementary data from our recent coffee–drug interaction clinical study showed some subjects had higher area under the plasma drug concentration ‐ time curve (AUC) and plasma peak drug concentration (Cmax) of the CYP3A4 probe felodipine compared to aqueous control. It was hypothesized that coffee might interact like grapefruit in responsive individuals. Beans from six geographical locations were consistently brewed into coffee that was separated chromatographically to a methanolic fraction for in vitro inhibition testing of CYP3A4 metabolism of felodipine at 1% coffee strength. The effect of simultaneous incubation and 10‐min preincubation with coffee fractions determined whether coffee had direct and mechanism‐based inhibitory activity. A subsequent five‐way randomized balanced controlled crossover clinical study evaluated the clinical pharmacokinetic interaction with single‐dose felodipine. Grapefruit juice, water, or three of the in vitro tested coffees were ingested at 300 mL alone 1 h before and then with felodipine. In vitro, all six coffees decreased felodipine metabolism for both simultaneous and preincubation exposure compared to corresponding control. Five coffees demonstrated mechanism‐based inhibition. Grapefruit increased felodipine AUC 0–8 (25 vs. 13 ng.h/mL, P

There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF.

Aims: Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos.\ud \ud Methods and results: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34–50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21–44%; P < 0.0001) and heart failure hospitalization (49%, 39–58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15–39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27–48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16–45%; P < 0.0001) for cardiovascular death, 46% (33–56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11–39%; P < 0.0001) for all-cause mortality.\ud \ud Conclusion: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.

Objective Our purpose was to study the changes in vasoconstrictive neurohormones, N-terminal proatrial natriuretic peptide (Nt-proANP), and brain natriuretic peptide (BNP) and their relationship with left ventricular (LV) remodeling soon after anterior myocardial infarction (MI). Background The Healing and Afterload Reducing Therapy (HEART) trial has shown that early use of ramipril improves left ventricular ejection fraction (LVEF) and attenuates LV remodeling when initiated soon after MI. This neurohumoral substudy of HEART investigates the changes in vasoconstrictive and natriuretic peptides and their relationship with LV remodeling. Methods One hundred twenty-two patients had blood drawn for the measurement of catecholamines, endothelin-I, angiotensin II, Nt-proANP and BNP, and prostacyclins within 24 hours of an MI, and at 3, 14, and 90 days after the MI. Quantitative echocardiograms were performed at baseline and at 14 days. Results All neurohormones except angiotensin II ( P = .12) and prostaglandins were significantly elevated at baseline. Vasoconstrictive neurohormones decreased significantly over time but remained elevated at 14 days. Both Nt-proANP and BNP were elevated within the first 14 days. BNP decreased significantly by 90 days, whereas Nt-proANP exhibited no change between 14 and 90 days. Ramipril decreased plasma levels of angiotensin II at 3 days but had no effect on the other neurohormones. Conclusions Neurohumoral activation occurs and persists in patients with anterior MI and overall preserved LV function. Ramipril had only a modest impact on neurohormones despite its significant benefits on LV remodeling soon after MI. (Am Heart J 2001;142:1056-64.)

© 2013 Paterson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Imaging has become a routine part of heart failure (HF) investigation. Echocardiography is a first-line test in HF given its availability and it provides valuable diagnostic and prognostic information. Cardiac magnetic resonance (CMR) is an emerging clinical tool in the management of patients with non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role in the detection of a variety of cardiomyopathies but there is a paucity of high quality evidence to support these recommendations. The primary objective of this study is to compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (that is, echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The primary hypothesisis that the routine use of CMR will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HF with preserved ejection fraction.Design: Tertiary care sites in Canada and Finland, with dedicated HF and CMR programs, will randomize consecutive patients with new or deteriorating HF to routine CMR or selective CMR. All patients will undergo a standard clinical echocardiogram and the interpreter will assign the most likely HF etiology. Those undergoing CMR will also have a standard examination and will be assigned a HF etiology based upon the findings. The treating physician's impression about non-ischemic HF etiology will be collected following all baseline testing (including echo ± CMR). Patients will be followed annually for 4 years to ascertain clinical outcomes, quality of life and cost. The expected outcome is that the routine CMR arm will have a significantly higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other' cardiomyopathy than the selective CMR group.Discussion: This study will be the first multicenter randomized, controlled trial evaluating the role of CMR in non-ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order to determine whether there are any gains over management strategies employing selective CMR utilization. The insight gained from this study should improve appropriate CMR use in HF. Trial registration: NCT01281384. © 2013 Paterson et al.; licensee BioMed Central Ltd.

Background This post hoc analysis of the HF-ACTION cohort explores the primary and secondary results of the HF-ACTION study by etiology and severity of illness. Methods HF-ACTION randomized stable outpatients with reduced left ventricular (LV) function and heart failure (HF) symptoms to either supervised exercise training plus usual care or to usual care alone. The primary outcome was all-cause mortality or all-cause hospitalization; secondary outcomes included all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or HF hospitalization. The interaction between treatment and risk variable, etiology or severity as determined by risk score, New York Heart Association class, and duration of cardiopulmonary exercise test was examined in a Cox proportional hazards model for all clinical end points. Results There was no interaction between etiology and treatment for the primary outcome ( P = .73), cardiovascular (CV) mortality or CV hospitalization ( P = .59), or CV mortality or HF hospitalization ( P = .07). There was a significant interaction between etiology and treatment for the outcome of mortality ( P = .03), but the interaction was no longer significant when adjusted for HF-ACTION adjustment model predictors ( P = .08). There was no significant interaction between treatment effect and severity, except a significant interaction between cardiopulmonary exercise duration and training was identified for the primary outcome of all-cause mortality or all-cause hospitalization. Conclusion Consideration of symptomatic (New York Heart Association classes II to IV) patients with HF with reduced LV function for participation in an exercise training program should be made independent of the cause of HF or the severity of the symptoms.

To assess the usefulness of incorporating a posture sensor into a ventricular inhibited rate modulated pacemaker, the hemodynamic effects of increasing the ventricular pacing rate with standing were studied in 15 pacemaker dependent patients aged 55 +/- 3.5 years. In a randomized cross-over design, the pacing rate remained at 70 or was increased to 100 beats/min immediately prior to standing. Blood pressure was monitored continuously and forearm blood flow was measured by venous occlusion plethysmography. There was no difference in supine blood pressure (117 +/- 4/63 +/- 3 compared to 118 +/- 5/64 +/- 4 mmHg) or forearm blood flow (2.88 +/- 0.36 vs 2.94 +/- 0.32 mL/100 mL/min) before the 70 or 100 pacing rate intervention. With standing, blood pressure fell to an equivalent degree at the two pacing rates (fall in mean blood pressure at 70 beats/min 6 +/- 4 and at 100 beats/min 8 +/- 2 mmHg, P = 0.7). After 1 minute of standing differences in blood pressure were similar, but after 2.5 minutes of standing the increase in mean blood pressure was less at 70 than at 100 beats/min (increase from control 28 +/- 2 compared to 36 +/- 3 mmHg, P = 0.002). Forearm blood flow decreased after standing for 1 and 2.5 minutes but there was no difference between the 70 and 100 pacing rates (fall in forearm blood flow at 2.5 minutes 0.50 +/- 0.24 and 0.59 +/- 0.25 mL/100 mL/cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

The Canadian Heart Rhythm Society in conjunction with the Canadian Cardiovascular Society is committed to the promotion of evidence-based practice in Canada. Since the last Canadian guidelines on the management of sudden cardiac death were published in 2000, several well-conducted clinical trials evaluating the implantable cardioverter defibrillator have been completed and published. The Canadian Cardiovascular Society Council has granted permission to review and update guidelines for the indications for implantable cardioverter defibrillators. Furthermore, data are emerging on the potential benefits of biventricular pacing therapy (cardiac resynchronization) for heart failure; recommendations for the use of this therapy have been included in the present paper. Ethical considerations and the economic implications of these recommendations are also included. Canada's heart rhythm specialists, represented by the Canadian Heart Rhythm Society, have been joined by two heart failure specialists, a medical ethicist and an economist, to develop the present position paper. Members of the Canadian Heart Rhythm Society participated in the discussion of these recommendations in open forum meetings and by electronic communication.

Cardiovascular disease is a major health issue for the elderly patient. Many diagnostic, therapeutic and ethical issues are specific for the the older adult with heart disease. The Canadian Cardiovascular Society 2002 Consensus Conference provides recommendations for the most frequently encountered cardiac problems in the elderly patient. A common theme of the recommendations is the need to apply the best evidence based medicine together with an assessment of frailty, comorbidity and quality of life. A major goal of the conference was to identify treatments that are not optimally used in the older patient.

Symptomatic heart failure (HF) affects 4.7 million patients in the U.S. with approximately 550,000 new cases identified annually.1-3 Proportionally, there are 428,000 patients in Canada, incurring $8 billion in annual hospital costs alone, an economic burden expected to double in the next 2 decades.4-6 Other forms of cardiovascular disorders are remaining stable, while the incidence of heart failure is increasing. This is partly the consequence of the successful management of acute heart failure, and partly due to an aging population. The rising prevalence of heart failure is occurring in the context of a persistent one-year mortality rate of between 25 and 40%.5