Journal of Cardiac Failure RSS feed: Articles in Press. Journal of Cardiac Failure publishes original, peer-reviewed communications of scientific excellence and review articles on clinical research, basic human studies, animal studies, and bench research with potential clinical applications to heart failure -pathogenesis, etiology, epidemiology, pathophysiological mechanisms, assessment, prevention, and treatment.http://www.onlinejcf.com//inpress?rss=yesElsevier Inc.en © 2010 Elsevier Inc. All rights reserved. Journal of Cardiac Failure1071-91642010-02-08 © 2010 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.onlinejcf.com/article/PIIS1071916409012172/abstract?rss=yesAbstract: Background: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways.Methods and Results: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm2, respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 ± 40 versus 168 ± 35 vessels/mm2; P < .05). Ejection fraction was not modified by stem cell therapy.Conclusions: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration - Corrected ProofMontserrat Rigol, Núria Solanes, Jordi Farré, Santiago Roura, Mercè Roqué, Antonio Berruezo, Neus Bellera, Laura Novensà, David Tamborero, Cristina Prat-Vidal, Ma Ángeles Huzman, Montserrat Batlle, Margo Hoefsloot, Marta Sitges, José Ramírez, Ana Paula Dantas, Anna Merino, Ginés Sanz, Josep Brugada, Antoni Bayés-Genís, Magda Heras10.1016/j.cardfail.2009.12.006Journal of Cardiac Failure (2010)2010-02-08Journal of Cardiac Failure2010-02-08http://www.onlinejcf.com/article/PIIS1071916409012305/abstract?rss=yesAbstract: Background: The relationship of peak exercise oxygen consumption (VO2) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO2 values and survival in HF patients with systolic dysfunction.Methods and Results: This study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by-breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 ± 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 ± 12%; mean body mass index 28.7 ± 5.4; 73% on β-blocker). Black patients had a significantly lower peak VO2 than white patients (14.2 ± 5.2 versus 16.4 ± 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO2 was significantly associated with survival in both racial groups.Conclusions: Black HF patients had significantly lower peak VO2, but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients.The Effects of Race on Peak Oxygen Consumption and Survival in Patients With Systolic Dysfunction - Corrected ProofSammy Elmariah, Lee R. Goldberg, Michael T. Allen, Andrew Kao10.1016/j.cardfail.2009.12.010Journal of Cardiac Failure (2010)2010-02-08Journal of Cardiac Failure2010-02-08http://www.onlinejcf.com/article/PIIS1071916409012329/abstract?rss=yesAbstract: Background: We performed a prospective, randomized investigation assessing the incremental effect of automated health monitoring (AHM) technology over and above that of a previously described nurse directed heart failure (HF) disease management program. The AHM system measured and transmitted body weight, blood pressure, and heart rate data as well as subjective patient self-assessments via a standard telephone line to a central server.Methods and Results: A total of 188 consented and eligible patients were randomized between intervention and control groups in 1:1 ratio. Subjects randomized to the control arm received the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) heart failure disease management program. Subjects randomized to the intervention arm received the SPAN-CHF disease management program in conjunction with the AHM system. The primary end point was prespecified as the relative event rate of HF hospitalization between intervention and control groups at 90 days. The relative event rate of HF hospitalization for the intervention group compared with controls was 0.50 (95%CI [0.25–0.99], P = .05).Conclusions: Short-term reductions in the heart failure hospitalization rate were associated with the use of automated home monitoring equipment. Long-term benefits in this model remain to be studied.A Multicenter Randomized Controlled Evaluation of Automated Home Monitoring and Telephonic Disease Management in Patients Recently Hospitalized for Congestive Heart Failure: The SPAN-CHF II Trial - Corrected ProofAndrew Weintraub, Douglas Gregory, Ayan R. Patel, Daniel Levine, David Venesy, Kathleen Perry, Christine Delano, Marvin A. Konstam10.1016/j.cardfail.2009.12.012Journal of Cardiac Failure (2010)2010-02-08Journal of Cardiac Failure2010-02-08http://www.onlinejcf.com/article/PIIS1071916409012330/abstract?rss=yesAbstract: Background: Alterations of endothelial nitric oxide synthase (eNOS) enzyme activity via eNOS gene polymorphisms have been associated with significant cardiovascular morbidity and mortality. Both the thymidine to cytosine transition mutation (T−786→C) in the promoter region and the missense mutation in the exon 7 coding region of the eNOS gene (G894→T) have been associated with several cardiovascular disease states. We hypothesized that heart transplant recipients who carried at least 1 allele of either of the polymorphisms would have reduced myocardial tissue expression of eNOS measured in the explanted heart.Methods and Results: Genomic DNA was isolated from myocardial tissue samples obtained from 43 explanted human hearts using standard methods. Regions of the eNOS gene were amplified from genomic DNA with a polymerase chain reaction using specific primers. Protein expression of eNOS was measured by Western blot analysis. There was a statistically significant decrease in mean eNOS expression in samples containing at least one allele for the T−786→C promoter polymorphism (P=.04) compared with patients homozygous for the T allele. There was no change in eNOS expression associated with the G894→T exonic polymorphisms.Conclusions: Our data show in failing human myocardium that the T−786→C promoter polymorphism is associated with reduced eNOS expression, whereas the G894→T polymorphism of exon 7 is not associated with change in either eNOS mRNA or protein expression. Reduced eNOS expression associated with the promoter polymorphism may contribute to the vascular, contractile, and autonomic responses to ventricular failure.A Promoter Polymorphism of the Endothelial Nitric Oxide Synthase Gene is Associated With Reduced mRNA and Protein Expression in Failing Human Myocardium - Corrected ProofAmit A. Doshi, Mark T. Ziolo, Honglan Wang, Emily Burke, Amanda Lesinski, Philip Binkley10.1016/j.cardfail.2009.12.013Journal of Cardiac Failure (2010)2010-02-08Journal of Cardiac Failure2010-02-08http://www.onlinejcf.com/article/PIIS1071916409012366/abstract?rss=yesAbstract: Background: Myocardial biopsy can be used for the detection of viral genome in dilated cardiomyopathy (DCM). Pilot studies have previously reported beneficial effects on clinical outcome and safety of an antiviral therapy using interferon β-1b in chronic viral DCM.Methods and Results: Myocardial biopsies were taken from patients with DCM. Using polymerase chain reaction and Southern Blot analysis, viral genome could be detected in 49% of patients. In 42 patients with viral infection, off-label use with interferon β-1b was initiated. A further 68 patients formed the control group. The outcome was evaluated after follow-up with echocardiography, exercise electrocardiogram, and New York Heart Association class. A total of 81 men and 29 women with a median left ventricular ejection fraction of 34% were included. The follow-up period was 36 months. In 33 (79%) patients with interferon β-1b treatment, minor adverse reactions occurred, but no major adverse events were reported. No significant benefit for interferon β-1b treatment on clinical outcome could be detected during follow-up.Conclusions: Off-label use with interferon β-1b in patients with viral DCM is feasible and safe under routine clinical practice. Concerning the herein evaluated clinical outcome parameters, promising results from pilot studies could not be confirmed. High prevalence of parvovirus B19 (92%) might influence the results.Interferon β-1b Therapy in Chronic Viral Dilated Cardiomyopathy—Is There a Role for Specific Therapy? - Corrected ProofOliver Zimmermann, Christoph Rodewald, Michael Radermacher, Martin Vetter, Juliane M. Wiehe, Magdalena Bienek-Ziolkowski, Vinzenz Hombach, Jan Torzewski10.1016/j.cardfail.2009.12.016Journal of Cardiac Failure (2010)2010-02-08Journal of Cardiac Failure2010-02-08http://www.onlinejcf.com/article/PIIS1071916409012159/abstract?rss=yesAbstract: Background: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks.Methods and Results: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF.Conclusions: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.What are the Thromboembolic Risks of Heart Failure Combined With Chronic or Paroxysmal AF? - Corrected ProofJane Cochrane Caldwell, Mamas A. Mamas, Ludwig Neyses, Clifford J. Garratt10.1016/j.cardfail.2009.12.004Journal of Cardiac Failure (2010)2010-02-05Journal of Cardiac Failure2010-02-05REVIEW ARTICLEhttp://www.onlinejcf.com/article/PIIS1071916409012287/abstract?rss=yesAbstract: Background: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block.Methods and Results: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO2max). Sixty patients were enrolled, and the mean follow-up period was 17.5 ± 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO2max were not significantly different. Death occurred more frequently with RVP.Conclusion: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode.Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study - Corrected ProofMartino Martinelli Filho, Sérgio Freitas de Siqueira, Roberto Costa, Oswaldo T. Greco, Luiz Felipe Moreira, Andre D'avila, E. Kevin Heist10.1016/j.cardfail.2009.12.008Journal of Cardiac Failure (2010)2010-02-05Journal of Cardiac Failure2010-02-05http://www.onlinejcf.com/article/PIIS1071916409012299/abstract?rss=yesAbstract: Background: Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics.Methods and Results: Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days.Conclusions: Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD - Corrected ProofMaria Rosa Costanzo, Mitchell T. Saltzberg, Mariell Jessup, John R. Teerlink, Paul A. Sobotka, Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (Unload) Investigators10.1016/j.cardfail.2009.12.009Journal of Cardiac Failure (2010)2010-02-05Journal of Cardiac Failure2010-02-05http://www.onlinejcf.com/article/PIIS1071916409011968/abstract?rss=yesAbstract: Background: The right ventricle normally operates as a low pressure, high-flow pump connected to a high-capacitance pulmonary vascular circuit. Morbidity and mortality in humans with pulmonary hypertension (PH) from any cause is increased in the presence of right ventricular (RV) dysfunction, but the differences in pathology of RV dysfunction in chronic versus acute occlusive PH are not widely recognized.Methods and Results: Chronic PH that develops over weeks to months leads to RV concentric hypertrophy without inflammation that may progress slowly to RV failure. In contrast, pulmonary embolism (PE) results in an abrupt vascular occlusion leading to increased pulmonary artery pressure within minutes to hours that causes immediate deformation of the RV. RV injury is secondary to mechanical stretch, shear force, and ischemia that together provoke a cytokine and chemokine-mediated inflammatory phenotype that amplifies injury.Conclusions: This review will briefly describe causes of pulmonary embolism and chronic PH, models of experimental study, and pulmonary vascular changes, and will focus on mechanisms of right ventricular dysfunction, contrasting mechanisms of RV adaptation and injury in these 2 settings.Right Ventricular Heart Failure From Pulmonary Embolism: Key Distinctions From Chronic Pulmonary Hypertension - Corrected ProofJohn A. Watts, Michael R. Marchick, Jeffrey A. Kline10.1016/j.cardfail.2009.11.008Journal of Cardiac Failure (2010)2010-01-18Journal of Cardiac Failure2010-01-18http://www.onlinejcf.com/article/PIIS1071916409012160/abstract?rss=yesAbstract: Background: Over the last 50 years left bundle branch block (LBBB) has been defined as homophasic (concordant: cLBBB) or heterophasic (discordant: dLBBB) when associated with a positive or negative T wave in leads I and V5-V6, respectively. LBBB is recognized as an adverse prognostic factor in heart failure (HF). The prevalence and clinical significance of cLBBB and dLBBB in HF patients are unknown.Methods and Results: A total of 897 consecutive systolic HF patients (age 65 ± 13 years, left ventricular ejection fraction [LVEF], 34 ± 10%) underwent clinical characterization, electrocardiographic evaluation for LBBB diagnosis and classification, and follow-up for cardiac events (median 37 months, range 1-84). LBBB was diagnosed in 232 patients (26%), cLBBB in 71 (31%), and dLBBB in 161 (69%). The dLBBB patients were older than those with cLBBB, and presented with lower LVEF, greater left ventricular telediastolic diameter and left ventricular mass index, higher level of brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, renin activity, and norepinephrine (all P < .05). At Kaplan-Meier analysis, LBBB (P = .003) and dLBBB (P = .036) were associated with a worse prognosis when the composite end point of sudden death and implantable cardioverter defibrillator shock was considered.Conclusions: In systolic HF, dLBBB is associated with a worse clinical, neurohormonal, and prognostic profile. LBBB classification could represent a useful tool in routine clinical evaluation.Concordant Versus Discordant Left Bundle Branch Block in Heart Failure Patients: Novel Clinical Value of an Old Electrocardiographic Diagnosis - Corrected ProofLuigi Padeletti, Alessandro Valleggi, Giuseppe Vergaro, Fabiana Lucà, Carmelo M. Rao, Laura Perrotta, Francesco Cappelli, Antonio L'abbate, Claudio Passino, Michele Emdin10.1016/j.cardfail.2009.12.005Journal of Cardiac Failure (2010)2010-01-18Journal of Cardiac Failure2010-01-18http://www.onlinejcf.com/article/PIIS1071916409012184/abstract?rss=yesPatients with type 2 diabetes mellitus (DM) are 2.5 times more likely to develop heart failure (HF) as compared with age- and sex-matched individuals without DM, with the relative risk increasing by 32% per unit increase in glycated hemoglobin. In elderly people without history of DM or HF, higher fasting glucose levels are associated with increased risk of incident HF. Conversely, HF itself is considered an insulin-resistant state and is associated with significant risk for developing DM. Given these relationships, it is not surprising that HF is present in more than 30% of all adults with DM, whereas DM is present in 45% of all HF patients, making overt DM a very common comorbidity in HF. Many more patients with HF may have insulin resistance or undiagnosed DM. Importantly, HF patients have worse outcomes if they have concomitant DM, especially if HF is of ischemic etiology because the ischemic cardiomyocytes largely rely on aerobic and anaerobic glycolysis and glucose utilization, an insulin-mediated process, that is impaired in this setting. Finally, considering the worsening population obesity trend, this problem is likely to get worse underscoring the need for efforts providing insights into therapeutic approaches for the management of this complex comorbid state.Metformin Use in Patients With Diabetes Mellitus and Heart Failure: Friend or Foe? - Corrected ProofGregory Giamouzis, Filippos Triposkiadis, Javed Butler10.1016/j.cardfail.2009.12.007Journal of Cardiac Failure (2010)2010-01-18Journal of Cardiac Failure2010-01-18EDITORIAL COMMENThttp://www.onlinejcf.com/article/PIIS107191640901197X/abstract?rss=yesAbstract: Background: The left ventricular assist device (LVAD) is a therapy for patients with end-stage heart failure, many of whom have a preexisting implantable cardioverter-defibrillator (ICD). We investigated whether the implantation of a LVAD affects ICD function.Methods and Results: Patients implanted with a LVAD between September 2000 and February 2009 were studied. Right ventricular (RV), right atrial, and left ventricular lead impedance, sensing, and capture thresholds were recorded before and after LVAD placement and subsequent lead-related interventions were noted. Of the 61 patients receiving a LVAD, data were collected from 30 patients who had preexisting ICDs. Significant pre-post differences were noted for all RV lead parameters: sensing amplitude decreased from 9.2±3.1 to 5.7±3.6 millivolts (P < .001); impedance decreased from 479±118 to 418±94 ohms (P=.008); and threshold increased from 4.3±6.7 to 11.0±16.8 microjoules (P=.021). As a result of alterations in lead parameters, 4 patients (13%) required lead revisions and 6 patients (20%) required ICD testing.Conclusions: Differences in ICD lead function were observed after LVAD placement resulting in clinically significant interventions. These data suggest that ICD interrogation be performed post-LVAD placement and that patients be counseled for the potential need for lead revisions and ICD testing when consented for a LVAD.Effect of Left Ventricular Assist Device Placement on Preexisting Implantable Cardioverter-defibrillator Leads - Corrected ProofAmrut V. Ambardekar, Christopher M. Lowery, Larry A. Allen, Anne P. Cannon, Joseph C. Cleveland, Joann Lindenfeld, Andreas Brieke, William H. Sauer10.1016/j.cardfail.2009.12.003Journal of Cardiac Failure (2010)2010-01-11Journal of Cardiac Failure2010-01-11http://www.onlinejcf.com/article/PIIS1071916409011907/abstract?rss=yesAbstract: Background: Low body temperature is an independent predictor of poor prognosis in patients with congestive heart failure. The cardiomyopathic hamster develops progressive biventricular dysfunction, resulting in heart failure death at 9 months to 1 year of life. Our goal was to use cardiomyopathic hamsters to examine the relationship between body temperature and heart failure decompensation and death.Methods and Results: To this end, we implanted temperature and activity transducers with telemetry into the peritoneal space of 46 male Bio-TO-2 Syrian cardiomyopathic hamsters. Multiple techniques, including computing mean temperature, frequency domain analysis, and nonlinear analysis, were used to determine the most useful method for predicting poor prognosis. Data from 44 hamsters were included in our final analysis. We detected a decline in core body temperature in 98% of the hamsters 8±4 days before death (P < .001). We examined the dominant frequency of temperature variation (ie, the circadian rhythm) by using cosinor analysis, which revealed a significant decrease in the amplitude of the body temperature circadian rhythm 8 weeks before death (0.28°C; 95% CI, 0.26-0.31) compared to baseline (0.36°C; 95% CI, 0.34-0.39; P=.005). The decline in the circadian temperature variation preceded all other evidence of decompensation.Conclusions: We conclude that a decrease in the amplitude of the body temperature circadian rhythm precedes fatal decompensation in cardiomyopathic hamsters. Continuous temperature monitoring may be useful in predicting preclinical decompensation in patients with heart failure and in identifying opportunities for therapeutic intervention.Circadian Body Temperature Variability is an Indicator of Poor Prognosis in Cardiomyopathic Hamsters - Corrected ProofAmany Ahmed, Sreedevi Gondi, Casey Cox, Suwei Wang, Igor V. Stupin, K.J. Shankar, Shahzeb M. Munir, Ed Sobash, Alan Brewer, James J. Ferguson, MaCarthur A. Elayda, S. Ward Casscells, James M. Wilson10.1016/j.cardfail.2009.11.004Journal of Cardiac Failure (2010)2010-01-07Journal of Cardiac Failure2010-01-07http://www.onlinejcf.com/article/PIIS1071916409011956/abstract?rss=yesAbstract: Background: Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients.Methods and Results: The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on β-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. β-blockers at baseline were associated with improved survival in patients with LVEF ≤40% independently of COPD.Conclusion: COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients.COPD Predicts Mortality in HF: The Norwegian Heart Failure Registry - Corrected ProofJonathan De Blois, Serge Simard, Dan Atar, Stefan Agewall, For the Norwegian Heart Failure Registry10.1016/j.cardfail.2009.12.002Journal of Cardiac Failure (2010)2010-01-07Journal of Cardiac Failure2010-01-07CLINICAL INVESTIGATIONhttp://www.onlinejcf.com/article/PIIS1071916409011919/abstract?rss=yesAbstract: Background: Despite advances in the treatment of chronic ambulatory heart failure, hospitalization rates for acute decompensated heart failure (ADHF) remain high. Although loop diuretics are used in nearly all patients with ADHF to relieve congestive symptoms, optimal dosing strategies remain poorly defined.Methods and Results: This was a prospective, randomized, parallel-group study comparing the effectiveness of continuous intravenous (cIV) with intermittent intravenous (iIV) infusion of furosemide in 56 patients with ADHF. The dose and duration of furosemide as well as concomitant medications to treat ADHF were determined by physician preference. The primary end point of the study was net urine output (nUOP)/24hours. Safety measures including electrolyte loss and hemodynamic instability were also assessed.Twenty-six patients received cIV and 30 patients received iIV dosing. The mean nUOP/24hours was 2098±1132mL in patients receiving cIV versus 1575±1100mL in the iIV group (P=.086). The cIV group had significantly greater total urine output (tUOP) with 3726±1121mL/24hours versus 2955±1267mL/24hours in the iIV group (P=.019) and tUOP/mg furosemide with 38.0±31.0mL/mg versus 22.2±12.5mL/mg (P=.021). Mean weight loss was not significantly different between the groups. The cIV group experienced a shorter length of hospital stay (6.9±3.7 versus 10.9±8.3 days, P=.006). There were no differences in safety measures between the groups.Conclusions: The cIV of furosemide was well tolerated and significantly more effective than iIV for tUOP. In addition, continuous infusion appears to provide more efficient diuresis.Continuous Versus Intermittent Infusion of Furosemide in Acute Decompensated Heart Failure - Corrected ProofMargaret R. Thomson, Jean M. Nappi, Steven P. Dunn, Ian B. Hollis, Jo E. Rodgers, Adrian B. Van Bakel10.1016/j.cardfail.2009.11.005Journal of Cardiac Failure (2010)2010-01-06Journal of Cardiac Failure2010-01-06http://www.onlinejcf.com/article/PIIS1071916409011944/abstract?rss=yesAbstract: Background: Although renin-angiotensin system (RAS) inhibitors have little demonstrable effect on mortality in patients with heart failure and preserved ejection fraction (HF-PEF), some trials have suggested a benefit with regard to reduction in HF hospitalization.Methods and Results: Here, we systematically review and evaluate prospective clinical studies of RAS inhibitors enrolling patients with HF-PEF, including the 3 major trials of RAS inhibition (Candesartan in Patients with Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction [CHARM-Preserved], Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction [I-PRESERVE], and Perindopril in Elderly People with Chronic Heart Failure [PEP-CHF]). We also conducted a pooled analysis of 8021 patients in the 3 major randomized trials of RAS inhibition in HF-PEF (CHARM-Preserved, I-PRESERVE, and PEP-CHF) in fixed-effect models, finding no clear benefit with regard to all-cause mortality (odds ratio [OR] 1.03, 95% confidence interval [CI], 0.92-1.15; P=.62), or HF hospitalization (OR 0.90, 95% CI 0.80-1.02; P=.09).Conclusions: Although RAS inhibition may be valuable in the management of comorbidities related to HF-PEF, RAS inhibition in HF-PEF is not associated with consistent reduction in HF hospitalization or mortality in this emerging cohort.The Effect of Renin-angiotensin System Inhibitors on Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction: A Systematic Review and Meta-analysis - Corrected ProofRavi V. Shah, Akshay S. Desai, Michael M. Givertz10.1016/j.cardfail.2009.11.007Journal of Cardiac Failure (2010)2010-01-06Journal of Cardiac Failure2010-01-06http://www.onlinejcf.com/article/PIIS1071916409011762/abstract?rss=yesAbstract: Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association.Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization.Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure - Corrected ProofLarry A. Allen, G. Michael Felker, Mandeep R. Mehra, Jun R. Chiong, Stephanie H. Dunlap, Jalal K. Ghali, Daniel J. Lenihan, Ron M. Oren, Lynne E. Wagoner, Todd A. Schwartz, Kirkwood F. Adams10.1016/j.cardfail.2009.11.003Journal of Cardiac Failure (2009)2009-12-28Journal of Cardiac Failure2009-12-28http://www.onlinejcf.com/article/PIIS1071916409011312/abstract?rss=yesAbstract: Background: The value between paced QRS duration (pQRSd) and native QRS duration (nQRSd) in paced population has not been compared. The relation between nQRSd and pQRSd remains undefined now.Methods and Results: A total of 310 right ventricular apex (RVA) paced patients were enrolled. The correlation coefficients between nQRSd and pQRSd to left ventricular (LV) dimensions and ejection fraction (LVEF) were calculated and then compared. The association between pQRSd and nQRSd was examined. pQRSd was better correlated with LVDD, LVDS, and LVEF than nQRSd in all patients or patients with no intraventricular conduction block (NIVCB, n = 136) or complete right bundle-branch block (CRBB, n = 86) (all P < .01). pQRSd was positively correlated with nQRSd in NIVCB, CRBB, and complete left bundle-branch block (CLBB, n = 45) patients (r = 0.408, 0.465, and 0.766, respectively; all P < .001). However, pQRSd was not different between NIVCB, CRBB, and CLBB patients (P > .05) after adjusting for LVEF and LV dimensions.Conclusions: pQRSd is superior to nQRSd in terms of reflecting LV structures and function in RVA-paced patients. Bundle branch block (BBB) has no significant effect on pQRSd and thus further studies are needed to clarify whether BBB is an independent risk factor for the development of heart failure after RVA pacing.Native and Paced QRS Duration in Right Ventricular Apex Paced Patients - Corrected ProofWenzhi Pan, Yangang Su, Aijun Sun, Xue Gong, Junbo Ge10.1016/j.cardfail.2009.10.021Journal of Cardiac Failure (2009)2009-12-11Journal of Cardiac Failure2009-12-11http://www.onlinejcf.com/article/PIIS1071916409011440/abstract?rss=yesAbstract: Background: Functional electrical stimulation (FES) improves exercise capacity and quality of life in chronic heart failure (CHF) patients. However, there is no evidence regarding the effectiveness of this treatment modality according to the severity of CHF. This study compares the effectiveness of FES on exercise capacity, endothelial function, neurohormonal status, and emotional stress in New York Heart Association (NYHA) III-IV versus NYHA II patients.Methods and Results: Eighteen NYHA II and 13 age- and sex-matched NYHA III-IV patients with stable CHF (left ventricular ejection fraction <35%) underwent a 6-week FES training program. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire, functional and overall), and emotional stress (Zung self-rating depression scale, Beck Depression Inventory), as well as plasma B-type natriuretic peptide (BNP), 6-minute walking distance test (6MWT), and endothelial function (flow-mediated dilatation [FMD]) were assessed at baseline and after completion of training protocol. 6MWT and plasma BNP improved significantly in 2 patient groups (both P < .001) after training program. The improvement of BNP was statistically greater in NYHA III-IV patients posttreatment than in those with NYHA II class (F=315.342, P < .001). Similarly, the improvement of 6MWT was statistically greater in NYHA III-IV group than in NYHA II patients (F=79.818, P < .001). Finally, an FES-induced greater improvement of FMD (F=9.517, P=.004) and emotional stress scores was observed in NYHA III-IV patients in comparison to NYHA II patients. There was a higher proportion of NYHA III-IV patients adhering to the FES training program for additional 3 months compared with the NYHA II group of patients (76.9% vs. 55.6%, P < .001).Conclusion: FES might exert a greater beneficial effect on clinical and neurohormonal status of NYHA III-IV patients in comparison to NYHA II patients. This effect may have important clinical relevance leading to increased adherence of severe CHF patients to exercise rehabilitation programs.Functional Electrical Stimulation is More Effective in Severe Symptomatic Heart Failure Patients and Improves Their Adherence to Rehabilitation Programs - Corrected ProofApostolos Karavidas, John T. Parissis, Vassiliki Matzaraki, Sophia Arapi, Christos Varounis, Ignatios Ikonomidis, Panagiotis Grillias, Ioannis Paraskevaidis, Vlassios Pirgakis, Gerasimos Filippatos, Dimitios T. Kremastinos10.1016/j.cardfail.2009.10.023Journal of Cardiac Failure (2009)2009-12-11Journal of Cardiac Failure2009-12-11CLINICAL INVESTIGATIONhttp://www.onlinejcf.com/article/PIIS1071916409011452/abstract?rss=yesAbstract: Background: The initiation of ventricular diastole is an energy-dependent phase of cardiac cycle. Delayed onset of left ventricular (LV) relaxation has been proposed to identify myocardial ischemia. Diabetes mellitus (DM) is known to be associated with coronary microangiopathy, but its influence on LV early relaxation is not established.Methods and Results: Ninety-two subjects consisting of 70 DM patients without overt cardiac disease and 22 normal controls were evaluated. Using strain rate imaging, time from R-wave on the electrocardiogram to onset of LV relaxation (Tr) was measured at rest and peak exercise. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest and peak exercise, enabling MBF reserve. Tr at rest was similar between DM patients and controls, but Tr at peak exercise was significantly longer in DM patients than controls. MBF reserve was significantly reduced in DM patients compared with controls. There was a significant negative correlation between Tr at peak exercise and MBF reserve. In a multivariate analysis, MBF reserve was an independent determinant of Tr at peak exercise.Conclusions: This study demonstrates that DM patients have exercise-induced delayed onset of LV relaxation in association with impaired coronary microcirculatory function in the absence of coexistent heart disease.Exercise-induced Delayed Onset of Left Ventricular Early Relaxation in Association With Coronary Microcirculatory Dysfunction in Patients With Diabetes Mellitus - Corrected ProofReiko Mizuno, Shinichi Fujimoto, Yoshihiko Saito, Shinobu Nakamura10.1016/j.cardfail.2009.10.024Journal of Cardiac Failure (2009)2009-12-11Journal of Cardiac Failure2009-12-11http://www.onlinejcf.com/article/PIIS1071916409011750/abstract?rss=yesAbstract: Background: Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support.Methods and Results: We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 ± 5 mm Hg, mean pulmonary artery pressure 36 ± 11 mm Hg, pulmonary capillary wedge pressure 23 ± 9 mm Hg, and cardiac index 2.0 ± 0.6 L·min·m2. Preoperatively, RV dysfunction was moderate (2.6 ± 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 ± 0.6 cm, and mid-RV was 3.5 ± 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 ± 0.9) failed to improve, despite reduced RV afterload.Conclusions: RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.Right Ventricular Dysfunction During Intensive Pharmacologic Unloading Persists After Mechanical Unloading - Corrected ProofMaryse Palardy, Anju Nohria, Jose Rivero, Neal Lakdawala, Patricia Campbell, Mahoto Kato, Leslie M. Griffin, Colleen M. Smith, Gregory S. Couper, Lynne W. Stevenson, Michael M. Givertz10.1016/j.cardfail.2009.11.002Journal of Cardiac Failure (2009)2009-12-11Journal of Cardiac Failure2009-12-11http://www.onlinejcf.com/article/PIIS1071916409011324/abstract?rss=yesAbstract: Background: Although 25% to 44% of patients with heart failure (HF) have diabetes mellitus (DM), the optimal treatment regimen for HF patients with DM is uncertain. We investigated the association between metformin therapy and outcomes in a cohort of advanced, systolic HF patients with DM.Methods and Results: Patients with DM and advanced, systolic HF (n = 401) were followed at a single university HF center between 1994 and 2008. The cohort was divided into 2 groups based on the presence or absence of metformin therapy. The cohort had a mean age of 56 ± 11 years, left ventricular ejection fraction (LVEF) of 24 ± 7%, with 42% being New York Heart Association (NYHA) III and 45% NYHA IV. Twenty-five percent (n = 99) were treated with metformin therapy. The groups treated and not treated with metformin were similar in terms of age, sex, baseline LVEF, medical history, and baseline glycosylated hemoglobin. Metformin-treated patients had a higher body mass index, lower creatinine, and were less often on insulin. One-year survival in metformin-treated and non-metformin-treated patients was 91% and 76%, respectively (RR = 0.37, CI 0.18-0.76, P = .007). After multivariate adjustment for demographics, cardiac function, renal function, and HF medications, metformin therapy was associated with a nonsignificant trend for improved survival.Conclusion: In patients with DM and advanced, systolic HF who are closely monitored, metformin therapy appears to be safe. Prospective studies are needed to determine whether metformin can improve HF outcome.Metformin Therapy and Outcomes in Patients With Advanced Systolic Heart Failure and Diabetes - Corrected ProofDigish D. Shah, Gregg C. Fonarow, Tamara B. Horwich10.1016/j.cardfail.2009.10.022Journal of Cardiac Failure (2009)2009-11-16Journal of Cardiac Failure2009-11-16CLINICAL INVESTIGATION