Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Patient perspectives on the use of mobile apps to support heart failure management: A qualitative descriptive study.

BACKGROUND: Adherence to diet and medical therapies are key to improving heart failure (HF) outcomes; however, nonadherence is common. While mobile apps may be a promising way to support patients with adherence via education and monitoring, HF patient perspectives regarding the use of apps for HF management in unknown. This data is critical for these tools to be successfully developed, implemented, and adopted to optimize adherence and improve HF outcomes. OBJECTIVE: To determine patients' needs, motivations, and challenges on the use of mobile apps to support HF management. METHODS: A qualitative descriptive study using focus groups (n = 4,60 minutes) was conducted among HF patients from outpatient HF clinics in Toronto, Canada. The Diffusion of Innovation theory informed a ten-question interview guide. Interview transcripts were independently coded by two researchers and analyzed using content analysis. RESULTS: Nineteen HF patients (65 ± 10 yrs, 12 men) identified a total of four key themes related to the use of mobile apps. The theme 'Factors impacting technology use by patients' identified motivations and challenges to app use, including access to credible information, easy and accessible user-interface. Three themes described patients' needs on the use of mobile apps to support HF management: 1) 'Providing patient support through access to information and self-monitoring', apps could provide education on HF-related content (e.g., diet, medication, symptoms); 2) 'Facilitating connection and communication', through information sharing with healthcare providers and connecting with other patients; 3) 'Patient preferences', app features such as reminders for medication, and visuals to show changes in HF symptoms were favoured. CONCLUSIONS: HF patients perceive several benefits and challenges to app use for HF self-management. Capitalizing on the benefits and addressing the challenges during the app development process may maximize adoption of such tools in this patient population.

Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial.

BACKGROUND: The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia-an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients. METHODS: We propose a randomized controlled crossover trial in patients with moderate HPS (PaO2 < 80 mmHg) and orthodeoxia (supine to upright PaO2 decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70-85% of the predicted peak work rate until the "stopping time" is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects. P < 0.05 will be considered statistically significant. DISCUSSION: HPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration and Results System (PRS) NCT04004104 . Registered on 1 July 2019.

Inhaled nitric oxide improves the hepatopulmonary syndrome: a physiologic analysis.

The hepatopulmonary syndrome (HPS) is defined by liver dysfunction, intrapulmonary vasodilatation and abnormal oxygenation. Hypoxaemia is progressive and liver transplant is the only effective treatment. Severe hypoxaemia is a life-threatening HPS complication, particularly after transplant. We evaluated gas-exchange and haemodynamic effects of invasive therapies in a consecutive sample of 26 pre-transplant patients. Inhaled nitric oxide significantly improved partial pressure of oxygen (12.4 mm Hg; p=0.001) without deleterious effects on cardiac output. Trendelenburg positioning resulted in a small improvement, and methylene blue did not, though individual responses were variable. Future studies should prospectively evaluate these strategies in severe post-transplant hypoxaemia.

CCS/CHFS Heart Failure Guidelines: Clinical Trial Update on Functional Mitral Regurgitation, SGLT2 Inhibitors, ARNI in HFpEF, and Tafamidis in Amyloidosis.

In this update, we focus on selected topics of high clinical relevance for health care providers who treat patients with heart failure (HF), on the basis of clinical trials published after 2017. Our objective was to review the evidence, and provide recommendations and practical tips regarding the management of candidates for the following HF therapies: (1) transcatheter mitral valve repair in HF with reduced ejection fraction; (2) a novel treatment for transthyretin amyloidosis or transthyretin cardiac amyloidosis; (3) angiotensin receptor-neprilysin inhibition in patients with HF and preserved ejection fraction (HFpEF); and (4) sodium glucose cotransport inhibitors for the prevention and treatment of HF in patients with and without type 2 diabetes. We emphasize the roles of optimal guideline-directed medical therapy and of multidisciplinary teams when considering transcatheter mitral valve repair, to ensure excellent evaluation and care of those patients. In the presence of suggestive clinical indices, health care providers should consider the possibility of cardiac amyloidosis and proceed with proper investigation. Tafamidis is the first agent shown in a prospective study to alter outcomes in patients with transthyretin cardiac amyloidosis. Patient subgroups with HFpEF might benefit from use of sacubitril/valsartan, however, further data are needed to clarify the effect of this therapy in patients with HFpEF. Sodium glucose cotransport inhibitors reduce the risk of incident HF, HF-related hospitalizations, and cardiovascular death in patients with type 2 diabetes and cardiovascular disease. A large clinical trial recently showed that dapagliflozin provides significant outcome benefits in well treated patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤ 40%), with or without type 2 diabetes.

Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial.

BACKGROUND: Thiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function. OBJECTIVE: We sought to determine whether oral thiamin supplementation improves left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life among patients with HF and reduced LVEF. METHODS: In this prospective, multicenter, double-blind, placebo-controlled randomized trial, eligible ambulatory patients with HF and reduced LVEF were recruited from 4 academic and community hospitals between 2010 and 2015. Participants were randomly assigned to receive either 200 mg oral thiamin mononitrate per day or placebo for 6 mo. RESULTS: Sixty-nine patients (mean ± SD age: 64 ± 12 y; 83% men; LVEF: 37% ± 11%) were randomly assigned: 34 received placebo and 35 received thiamin supplementation. Erythrocyte thiamin pyrophosphate and urine thiamin concentrations were significantly higher in the supplemented group than in the placebo group at 6 mo (P = 0.02 and <0.001, respectively). At 6 mo, LVEF was significantly higher in the placebo group than in the thiamin group (38%; 95% CI: 36%, 39% compared with 35%; 95% CI: 33%, 37%, P = 0.047) after adjusting for baseline measurements. There were no significant differences in Minnesota Living with Heart Failure score, distance walked in 6 min, and N-terminal prohormone of brain natriuretic peptide concentrations between the 2 groups. One patient (2.9%) in the thiamin-supplemented group and none in the control group died at 6 mo. CONCLUSIONS: In ambulatory patients with HF and reduced LVEF, thiamin supplementation for 6 mo did not improve LVEF, quality of life, or exercise capacity, despite increases in thiamin concentrations. These findings do not support routine thiamin supplementation in the treatment of HF and reduced LVEF.This trial was registered at clinicaltrials.gov as NCT00959075.

Prevalence of Thiamin Deficiency in Ambulatory Patients with Heart Failure.

BACKGROUND: Thiamin is a required coenzyme in energy production reactions that fuel myocardial contraction. Therefore, thiamin deficiency (TD) may aggravate cardiac dysfunction in patients with systolic heart failure (HF). OBJECTIVE: To determine the prevalence of TD in ambulatory participants with HF as well as the relationships between thiamin status and HF severity, dietary thiamin intake, diuretic use, and circulating neurohormones. DESIGN: A cross-sectional study comparing the prevalence of TD in ambulatory patients with HF with that of controls. Demographic, anthropometric, nutrition, medication use, and heart function data were collected from direct interviewing, questionnaires, and medical records. Blood samples were obtained to measure levels of neurohormones and assess TD. PARTICIPANTS/SETTING: Fifty age-matched control participants without HF and 100 outpatients with HF and reduced left ventricular function were recruited from clinics at St Michael's Hospital, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada, between September 2009 and February 2011. MAIN OUTCOME MEASURES: To assess TD, erythrocyte thiamin pyrophosphate (TPP) was measured using high-performance liquid chromatography. TD was defined as TPP<6.07 µg/dL (180 nmol/L). STATISTICAL ANALYSES PERFORMED: Prevalence rates were analyzed using χ2 test. Nonparametric statistics (Jonckheere-Terpstra, Kruskal-Wallis, Spearman's correlation) were used to assess TPP levels in relation to HF severity, medication use and plasma concentrations of F2-isoprostanes, norepinephrine, and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: There was no significant difference in the prevalence of TD in outpatients with HF (6%) and controls (6%) (P=0.99). No relationship was found between heart function, thiamin intake, use or dose of diuretics, and TD. A positive relationship was observed between erythrocyte TPP and F2-isoprostane levels (rs=0.22, P=0.03) but not between erythrocyte TPP and norepinephrine (P=0.45) and NT-proBNP (P=0.58). CONCLUSION: The prevalence of TD was low in ambulatory HF participants suggesting that, unlike hospitalized patients, ambulatory patients may be at a low risk for TD.

2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure.

Since the inception of the Canadian Cardiovascular Society heart failure (HF) guidelines in 2006, much has changed in the care for patients with HF. Over the past decade, the HF Guidelines Committee has published regular updates. However, because of the major changes that have occurred, the Guidelines Committee believes that a comprehensive reassessment of the HF management recommendations is presently needed, with a view to producing a full and complete set of updated guidelines. The primary and secondary Canadian Cardiovascular Society HF panel members as well as external experts have reviewed clinically relevant literature to provide guidance for the practicing clinician. The 2017 HF guidelines provide updated guidance on the diagnosis and management (self-care, pharmacologic, nonpharmacologic, device, and referral) that should aid in day-to-day decisions for caring for patients with HF. Among specific issues covered are risk scores, the differences in management for HF with preserved vs reduced ejection fraction, exercise and rehabilitation, implantable devices, revascularization, right ventricular dysfunction, anemia, and iron deficiency, cardiorenal syndrome, sleep apnea, cardiomyopathies, HF in pregnancy, cardio-oncology, and myocarditis. We devoted attention to strategies and treatments to prevent HF, to the organization of HF care, comorbidity management, as well as practical issues around the timing of referral and follow-up care. Recognition and treatment of advanced HF is another important aspect of this update, including how to select advanced therapies as well as end of life considerations. Finally, we acknowledge the remaining gaps in evidence that need to be filled by future research.

Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model.

BACKGROUND: The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. METHODS AND RESULTS: Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus tachycardia rates were significantly reduced after RDN. CONCLUSIONS: RDN in the infarcted pig model leads to reduction of postinfarction VAs and myocardial sympathetic effectors. This may form the basis for a potential therapeutic role of RDN in postinfarct VAs.

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications.

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Focus Update: anemia, biomarkers, and recent therapeutic trial implications.

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides discussion on the management recommendations on 3 focused areas: (1) anemia; (2) biomarkers, especially natriuretic peptides; and (3) clinical trials that might change practice in the management of patients with heart failure. First, all patients with heart failure and anemia should be investigated for reversible causes of anemia. Second, patients with chronic stable heart failure should undergo natriuretic peptide testing. Third, considerations should be given to treat selected patients with heart failure and preserved systolic function with a mineralocorticoid receptor antagonist and to treat patients with heart failure and reduced ejection fraction with an angiotensin receptor/neprilysin inhibitor, when the drug is approved. As with updates in previous years, the topics were chosen in response to stakeholder feedback. The 2014 Update includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers to best manage patients with heart failure.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update: focus on rehabilitation and exercise and surgical coronary revascularization.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides focused discussions on the management recommendations on 2 topics: (1) exercise and rehabilitation; and (2) surgical coronary revascularization in patients with heart failure. First, all patients with stable New York Heart Association class I-III symptoms should be considered for enrollment in a tailored exercise training program, to improve exercise tolerance and quality of life. Second, selected patients with suitable coronary anatomy should be considered for bypass graft surgery. As in previous updates, the topics were chosen in response to stakeholder feedback. The 2013 Update also includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers manage their patients with heart failure.

Dantrolene improves survival after ventricular fibrillation by mitigating impaired calcium handling in animal models.

BACKGROUND: Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. METHODS AND RESULTS: VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21 ± 6 s versus 181 ± 57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 µmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024 ± 0.013 versus 0.12 ± 0.02 arbitrary unit [200-ms cycle length], P=0.001). CONCLUSIONS: Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.

Computed tomographic coronary angiography for patients with heart failure (CTA-HF): a randomized controlled trial (IMAGE HF Project 1-C).

BACKGROUND: The prevalence of heart failure (HF) is rising in industrialized and developing countries. Though invasive coronary angiography (ICA) remains the gold standard for anatomical assessment of coronary artery disease in HF patients, alternatives are being sought. Computed tomographic coronary angiography (CTA) has emerged as an accurate non-invasive diagnostic tool for coronary artery disease (CAD) and has been demonstrated to have prognostic value. Whether or not CTA can be used in HF patients is unknown. Acknowledging the aging population, the growing prevalence of HF and the increasing financial burden of healthcare, we need to identify non-invasive diagnostic tests that are available, safe, accurate and cost-effective. METHODS/DESIGN: The proposed study aims to provide insight into the efficacy of CTA in HF patients. A multicenter randomized controlled trial will enroll 250 HF patients requiring coronary anatomical definition. Enrolled patients will be randomized to either CTA or ICA (n = 125 per group) as the first test to define coronary anatomy. The primary outcomes will be collected to determine downstream resource utilization. Secondary outcomes will include the composite clinical events and major adverse cardiac events. In addition, the accuracy of CTA for detecting coronary anatomy and obstruction will be assessed in patients who subsequently undergo both CTA and ICA. It is expected that CTA will be a more cost-effective strategy for diagnosis: yielding similar outcomes with fewer procedural risks and improved resource utilization. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01283659. Team grant #CIF 99470.

Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation.

BACKGROUND: For the primary prevention of sudden cardiac death, guidelines provide left ventricular ejection fraction (EF) criteria for implantable cardioverter defibrillator (ICD) placement without specifying the technique by which it should be measured. We sought to investigate the potential impact of performing cardiovascular magnetic resonance (CMR) for EF on ICD eligibility. METHODS: The study population consisted of patients being considered for ICD implantation who were referred for EF assessment by CMR. Patients who underwent CMR within 30 days of echocardiography were included. Echocardiographic EF was determined by Simpson's biplane method and CMR EF was measured by Simpson's summation of discs method. RESULTS: Fifty-two patients (age 62±15 years, 81% male) had a mean EF of 38 ± 14% by echocardiography and 35 ± 14% by CMR. CMR had greater reproducibility than echocardiography for both intra-observer (ICC, 0.98 vs 0.94) and inter-observer comparisons (ICC 0.99 vs 0.93). The limits of agreement comparing CMR and echocardiographic EF were - 16 to +10 percentage points. CMR resulted in 11 of 52 (21%) and 5 of 52 (10%) of patients being reclassified regarding ICD eligibility at the EF thresholds of 35 and 30% respectively. Among patients with an echocardiographic EF of between 25 and 40%, 9 of 22 (41%) were reclassified by CMR at either the 35 or 30% threshold. Echocardiography identified only 1 of the 6 patients with left ventricular thrombus noted incidentally on CMR. CONCLUSIONS: CMR resulted in 21% of patients being reclassified regarding ICD eligibility when strict EF criteria were used. In addition, CMR detected unexpected left ventricular thrombus in almost 10% of patients. Our findings suggest that the use of CMR for EF assessment may have a substantial impact on management in patients being considered for ICD implantation.

Cardiac sympathetic activation in patients with pulmonary arterial hypertension.

Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 ± 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 ± 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 ± 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 ± 2.2 vs. 1.5 ± 0.9 pmol/ml; P < 0.01) but similar to that seen in those with CHF (3.3 ± 1.4; P = NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure.

Role of KATP channels in the maintenance of ventricular fibrillation in cardiomyopathic human hearts.

RATIONALE: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. OBJECTIVE: We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. METHODS AND RESULTS: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 µmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia). CONCLUSIONS: K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.

A high-sodium diet is associated with acute decompensated heart failure in ambulatory heart failure patients: a prospective follow-up study.

BACKGROUND: A low-sodium diet is an accepted treatment of patients with heart failure (HF), although minimal evidence exists on the appropriate amount of sodium intake for this population. Certain HF guidelines have liberalized dietary sodium recommendations, which actually exceed guidelines for healthy adults. OBJECTIVES: We tested the hypothesis that high sodium intake is related to acute decompensated HF (ADHF) in ambulatory HF patients. Secondary outcomes included all-cause hospitalization and mortality. DESIGN: We prospectively enrolled medically stable, ambulatory patients with systolic HF (n = 123; mean ± SD age: 60 ± 13 y) from 2 outpatient HF clinics from 2003 to 2007. Baseline estimates of dietary sodium and other nutrient intakes were obtained from two 3-d food records. RESULTS: The median follow-up time was 3.0 y. Mean (±SD) sodium intakes were 1.4 ± 0.3, 2.4 ± 0.3, and 3.8 ± 0.8 g Na/d in the lower, middle, and upper tertiles, respectively. Cumulative ADHF event rates at 3 y were 12 ± 6%, 15 ± 7%, and 46 ± 11% in the low, middle, and upper tertiles, respectively (log-rank P = 0.001). For ADHF, the upper tertile was associated with an adjusted hazard ratio of 2.55 (95% CI: 1.61, 4.04; P < 0.001). Time-to-event probabilities were significant for mortality (log-rank P = 0.022) but not for all-cause hospitalization (log-rank P = 0.224). The high-sodium tertile was associated with an adjusted hazard ratio of 1.39 (95% CI: 1.06, 1.83; P = 0.018) for all-cause hospitalization and 3.54 (95% CI: 1.46, 8.62; P = 0.005) for mortality. CONCLUSIONS: To our knowledge, this study provides the first prospective evidence that ambulatory HF patients who consume higher amounts of sodium are at greater risk of an ADHF event. These data provide support for more stringent sodium intake guidelines than those currently recommended for HF patients.