Journal of Cardiac Failure RSS feed: Current Issue. 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/?rss=yesElsevier Inc.en © 2010 Elsevier Inc. All rights reserved. Journal of Cardiac Failure1071-9164169September 2010 © 2010 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.onlinejcf.com/article/PIIS1071916410002022/abstract?rss=yesAbstract: Background: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V3 is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation.Methods and Results: A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements.Conclusions: The V3 trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT.Addition of a Second LV Pacing Site in CRT Nonresponders Rationale and Design of the Multicenter Randomized V3 TrialPierre Bordachar, Christine Alonso, Frederic Anselme, Serge Boveda, Pascal Defaye, Stephane Garrigue, Daniel Gras, Didier Klug, Olivier Piot, Nicolas Sadoul, Christophe Leclercq10.1016/j.cardfail.2010.04.010Journal of Cardiac Failure 16, 9 (2010)2010-06-07Journal of Cardiac Failure2010-06-07169S1071-9164(10)X0011-2Clinical Trials709713http://www.onlinejcf.com/article/PIIS107191641000196X/abstract?rss=yesAbstract: Background: Worsening renal function (WRF) portends a poor prognosis, and recent deterioration in creatinine might identify patients with elevated intrarenal adenosine in whom adenosine A1 antagonism may improve renal hemodynamics and function. The purpose of this pilot study was to assess whether rolofylline, an adenosine A1 antagonist (A1RA), would facilitate diuresis while maintaining renal function in patients with acutely decompensated heart failure (ADHF) and recent WRF.Methods and Results: Seventy-six patients with ADHF, volume overload, and recent renal deterioration received rolofylline (30 mg, n = 36) or placebo (n = 40) for 3 days. Rolofylline did not demonstrate a beneficial effect on the primary end points of worsening heart failure or renal function after admission or death or readmission within 30 days. Similar proportions of patients receiving rolofylline (33%) and placebo (30%) were treatment failures within 30 days. However, persistent renal impairment (through Day 14) tended to be less common with rolofylline (6%) than placebo (18%). At Day 14, 11 patients receiving placebo and 13 patients receiving rolofylline had a decrease in creatinine ≥0.3 mg/dL. There were fewer heart failure readmissions with rolofylline (n = 2) than with placebo (n = 7) through Day 60.Conclusions: The Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized with Worsening Renal Function and Heart Failure Requiring Intravenous Therapy (ie, REACH UP) study did not demonstrate any clear benefit of rolofylline in patients with ADHF and worsening renal function. However, beneficial trends raise the possibility that A1RAs might prevent renal dysfunction in these high risk patients. To test this hypothesis, further larger studies need to evaluate the effects of adenosine A1 antagonists in patients with progressive renal dysfunction in the face of active heart failure therapy.The Effects of Adenosine A1 Receptor Antagonism in Patients With Acute Decompensated Heart Failure and Worsening Renal Function: The REACH UP StudyStephen S. Gottlieb, Michael M. Givertz, Marco Metra, Kevin Gergich, Steven Bird, Charlotte Jones-Burton, Barry Massie, Gad Cotter, Piotr Ponikowski, Beth Weatherley, Christopher O'Connor, Howard Dittrich10.1016/j.cardfail.2010.04.006Journal of Cardiac Failure 16, 9 (2010)2010-06-07Journal of Cardiac Failure2010-06-07169S1071-9164(10)X0011-2Clinical Trials714719http://www.onlinejcf.com/article/PIIS1071916410001983/abstract?rss=yesAbstract: Background: Although nesiritide is a potent vasodilator, studies using myocytes and isolated muscle strips have shown that recombinant B-type natriuretic peptide (BNP; nesiritide) decreases contractility. We sought to determine whether nesiritide decreases contractility in heart failure patients.Methods and Results: Twenty-five heart failure patients underwent left heart catheterization (using a pressure-volume conductance catheter) and echocardiography at baseline and after a 2 mcg/kg bolus and 30-minute nesiritide infusion (0.01 mcg·kg·min). From invasive and noninvasive measurements, left ventricular (LV) systolic function indices were calculated, including ejection fraction, end-systolic elastance (Ees; single-beat invasive and noninvasive methods) and preload-recruitable stroke work (PRSW; noninvasive, single-beat method). The mean age was 60 ± 11 years, 48% were male, 56% had coronary disease, and 64% had hypertension. Although nesiritide did not change LV ejection fraction, it did decrease contractility on pressure-volume analysis. Noninvasive Ees decreased from 2.6 ± 1.6 to 2.0 ± 1.4 mm Hg/mL (P = .02). For those with reduced ejection fraction, Ees decreased by invasive (P = .006) and noninvasive (P = .02) methods. PRSW decreased from 76 ± 37 to 62 ± 28 g/cm2 (P = .003). On tissue Doppler imaging, nesiritide reduced the systolic annular tissue velocity of the mitral annulus from 8.0 ± 1.9 to 6.9 ± 1.3 cm/s (P = .04).Conclusions: Nesiritide infusion acutely decreases derived measures of contractility and systolic function in patients with chronic heart failure.Acute Effects of Intravenous Nesiritide on Cardiac Contractility in Heart FailureSanjiv J. Shah, Andrew D. Michaels10.1016/j.cardfail.2010.04.008Journal of Cardiac Failure 16, 9 (2010)2010-06-02Journal of Cardiac Failure2010-06-02169S1071-9164(10)X0011-2Clinical Investigations720727http://www.onlinejcf.com/article/PIIS1071916410002046/abstract?rss=yesAbstract: Background: The association between sleep-disordered breathing (SDB) assessed by polysomnography and cardiac sympathetic nerve activity (SNA) assessed by cardiac iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging has not been investigated in patients with chronic heart failure (CHF).Methods and Results: We performed cardiac 123I-MIBG scintigraphy and overnight polysomnography in 59 patients with stable CHF. The patients were classified into the 3 groups: 19 with no or mild SDB (NM-SDB, apnea-hypopnea index <15); 21 with central sleep apnea (CSA), and 19 with obstructive sleep apnea (OSA). The cardiac washout rate (WR) of 123I-MIBG was obtained from initial and delayed planar 123I-MIBG images. The WR was higher in patients with CSA (54.2 ± 11.6%) than in those with OSA (37.9 ± 8.6%, P < .05) or NM-SDB (40.8 ± 8.8%, P < .05). The WR correlated positively with central apnea index (ρ = 0.40, P = .002). A stepwise multiple regression analysis selected CSA and plasma brain natriuretic peptide levels as independent variables associated with the WR.Conclusions: The WR was higher in CHF patients with CSA than in those with OSA or NM-SDB, and CSA was independently associated with the WR, suggesting a link of CSA to increased cardiac SNA in CHF.Washout Rate of Cardiac Iodine-123 Metaiodobenzylguanidine is High in Chronic Heart Failure Patients With Central Sleep ApneaAkira Tamura, Shinichi Ando, Yukie Goto, Yoshiyuki Kawano, Kazuhiro Shinozaki, Munenori Kotoku, Junichi Kadota10.1016/j.cardfail.2010.04.012Journal of Cardiac Failure 16, 9 (2010)2010-06-11Journal of Cardiac Failure2010-06-11169S1071-9164(10)X0011-2Clinical Investigations728733http://www.onlinejcf.com/article/PIIS1071916410002010/abstract?rss=yesAbstract: Background: Implantable cardioverter-defibrillators (ICDs) improve survival and are cost-effective in adults with poor left ventricular function. Because of differences in heart failure etiology, sudden death rates, and ICD complication rates, these findings may not be applicable to children.Methods and Results: We developed a Markov model to compare typical management of childhood dilated cardiomyopathy with symptomatic heart failure to prophylactic ICD implantation plus typical management. Model costs included costs of outpatient care, medications, complications, and transplantation. Time horizon was up to 20 years from model entry. Total costs were $433,000 (ICD strategy) and $355,000 (typical management). Although quality adjusted survival was greater in the ICD group (6.78 versus 6.43 quality adjusted life-years [QALY]), the incremental cost-utility ratio was $281,622/QALY saved with the ICD strategy. In sensitivity analyses, the ICD strategy cost less than the $100,000/QALY benchmark for cost-effectiveness only when the annual probability of sudden death exceeded 13% or when strong, sustained benefits in quality of life from the ICD were assumed.Conclusions: Prophylactic ICD use in children with dilated cardiomyopathy, poor ventricular function, and symptomatic heart failure does not appear to be cost-effective. This is likely due to lower sudden death rates in this population.Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Children With Dilated CardiomyopathyBrian Feingold, Gaurav Arora, Steven A. Webber, Kenneth J. Smith10.1016/j.cardfail.2010.04.009Journal of Cardiac Failure 16, 9 (2010)2010-06-07Journal of Cardiac Failure2010-06-07169S1071-9164(10)X0011-2Clinical Investigations734741http://www.onlinejcf.com/article/PIIS1071916410002034/abstract?rss=yesAbstract: Background: Complementary therapies such as yoga practice have become commonplace, yet the safety, physical, and psychological effects on patients with heart failure (HF) are unknown. The purpose of this study was to determine whether an 8-week yoga program was safe and would positively influence physical and psychological function in HF patients.Methods and Results: Stable HF patients were recruited (n = 15) and completed (n = 12) 8 weeks of yoga classes. Data collected were: safety (cardiac and orthopedic adverse events); physical function (strength, balance, endurance, flexibility); and psychological function (quality of life [QOL], depression scores, mindfulness) before and after 8 weeks of yoga classes.Results: Mean age was 52.4 ± 11.6 with three-fourths (n = 9) being male and Caucasian. No participant had any adverse events. Endurance (P < .02) and strength (upper P = .04 and lower body P = .01) significantly improved. Balance improved by 13.6 seconds (26.9 ± 19.7 to 40.0 ± 18.5; P = .05). Symptom stability, a subscale of QOL, improved significantly (P = .02). Although no subject was depressed, overall mood was improved. Subjects subjectively reported improvements in overall well-being.Conclusions: Yoga practice was safe, with participants experiencing improved physical function and symptom stability. Larger studies are warranted to provide more nonpharmacological options for improved outcomes in patients with HF.Yoga in Heart Failure Patients: A Pilot StudyJill Howie-Esquivel, Jiyeon Lee, Gina Collier, Wolf Mehling, Kirsten Fleischmann10.1016/j.cardfail.2010.04.011Journal of Cardiac Failure 16, 9 (2010)2010-06-07Journal of Cardiac Failure2010-06-07169S1071-9164(10)X0011-2Clinical Investigations742749http://www.onlinejcf.com/article/PIIS1071916410001971/abstract?rss=yesAbstract: Background: The purpose of this study was to evaluate whether dysfunction of specific cognitive abilities is a predictor of impending mortality in adults with systolic heart failure (HF).Methods: A total of 166 stable outpatients with HF completed cognitive function evaluation in language, working memory, memory, visuospatial ability, psychomotor speed, and executive function using a neuropsychological test battery. Demographic and clinical variables, comorbidity, depressive symptoms, and health-related quality of life were also measured. Patients were followed for 12 months to determine all-cause mortality.Results: There were 145 survivors and 21 deaths. In logistic regression analyses, significant predictors of mortality were lower left ventricular ejection fraction (LVEF) and poorer scores on measures of global congnitive function Mini-Mental State Examination [MMSE], working memory, memory, psychomotor speed, and executive function. Memory loss was the most predictive cognitive function variable (overall χ2 = 17.97, df = 2, P < .001; Nagelkerke R2 = 0.20). Gender was a significant covariate in 2 models, with men more likely to die. Age, comorbidity, depressive symptoms, and health-related quality of life were not significant predictors. In further analyses, significant predictors of mortality were lower systolic blood pressure and poorer global cognitive function, working memory, memory, psychomotor speed, and executive function, with memory being the most predictive.Conclusions: As hypothesized, lower LVEF and memory dysfunction predicted mortality. Poorer global cognitive score as determined by the MMSE, working memory, psychomotor speed, and executive function were also significant predictors. LVEF or systolic blood pressure had similar predictive values. Interventions are urgently needed to prevent and manage memory loss in HF.Memory Dysfunction, Psychomotor Slowing, and Decreased Executive Function Predict Mortality in Patients With Heart Failure and Low Ejection FractionSusan J. Pressler, Jinshil Kim, Penny Riley, David L. Ronis, Irmina Gradus-Pizlo10.1016/j.cardfail.2010.04.007Journal of Cardiac Failure 16, 9 (2010)2010-06-07Journal of Cardiac Failure2010-06-07169S1071-9164(10)X0011-2Clinical Investigations750760http://www.onlinejcf.com/article/PIIS1071916410002496/abstract?rss=yesAbstract: Background: A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more than a century. HF is also closely linked to abnormal glucose regulation (AGR) and insulin resistance (IR) in patients without DM and, similarly, these conditions commonly coexist. In epidemiological studies, each condition appears to predict the other. The prevalence of AGR/IR in HF patients without DM is significantly underrecognized and, as yet, the optimal method for screening for these abnormalities in the outpatient setting is unclear.Methods and Results: The purpose of this review is to overview the prevalence and prognostic impact of AGR and IR in HF patients without DM and discuss potential pathophysiological pathways that link these conditions with HF. The severity of glucose intolerance in patients with HF correlates with functional and clinical severity of HF and is an independent predictor of an adverse outcome. It is thought that changes in cardiac metabolism, including a switch from glucose metabolism toward fatty acid metabolism, may in part contribute to the pathophysiological processes associated with HF patients with AGR/IR.Conclusions: We discuss how pharmacological targeting of metabolic pathways in the myocardium of these patients with HF may represent novel therapeutic strategies in these at-risk patients.Impaired Glucose Tolerance and Insulin Resistance in Heart Failure: Underrecognized and Undertreated?Mamas A. Mamas, Christi Deaton, Martin K. Rutter, Martin Yuille, Simon G. Williams, Simon G. Ray, John New, J. Martin Gibson, Ludwig Neyses10.1016/j.cardfail.2010.05.027Journal of Cardiac Failure 16, 9 (2010)2010-07-22Journal of Cardiac Failure2010-07-22169S1071-9164(10)X0011-2Review Article761768http://www.onlinejcf.com/article/PIIS1071916410002113/abstract?rss=yesAbstract: Background: Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog.Methods and Results: MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients.Conclusions: Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function.Mast Cell Stabilization Decreases Cardiomyocyte and LV Function in Dogs With Isolated Mitral RegurgitationBetty Pat, Cheryl Killingsworth, Yuanwen Chen, James D. Gladden, Greg Walcott, Pamela C. Powell, Thomas Denney, Himanshu Gupta, Ravi Desai, Michael Tillson, A. Ray Dillon, Louis J. Dell'Italia10.1016/j.cardfail.2010.05.005Journal of Cardiac Failure 16, 9 (2010)2010-07-02Journal of Cardiac Failure2010-07-02169S1071-9164(10)X0011-2Basic Science and Experimental Studies769776http://www.onlinejcf.com/article/PIIS1071916410001715/abstract?rss=yesAbstract: Background: There is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, after permanent coronary artery ligation or sham operation.Methods and Results: Coronary artery ligation resulting in MI between 25% to 50% of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On postoperative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit+ cells in the border region.Conclusions: These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling.Effects of ACE2 Inhibition in the Post-Myocardial Infarction HeartMyung-A. Kim, Dongheon Yang, Keisuke Kida, Natalia Molotkova, Seon Ju Yeo, Nissi Varki, Michikado Iwata, Nancy D. Dalton, Kirk L. Peterson, Wolf-Eberhard Siems, Thomas Walther, Randy T. Cowling, John Kjekshus, Barry Greenberg10.1016/j.cardfail.2010.04.002Journal of Cardiac Failure 16, 9 (2010)2010-05-24Journal of Cardiac Failure2010-05-24169S1071-9164(10)X0011-2Basic Science and Experimental Studies777785http://www.onlinejcf.com/article/PIIS107191641000151X/abstract?rss=yesAbstract: Background: The complete removal of the cardiac sodium-calcium exchanger (NCX1) is associated with embryonic lethality, whereas its overexpression is linked to heart failure. To determine whether or not a reduced expression of NCX1 is compatible with normal heart structure and function, we studied 2 knockout (KO) mouse models with reduced levels of NCX1: a heterozygous global KO (HG-KO) with a 50% level of NCX1 expression in all myocytes, and a ventricular-specific KO (V-KO) with NCX1 expression in only 10% to 20% of the myocytes.Methods and Results: Both groups of mice were evaluated at baseline, after transaortic constriction (TAC), and after acute or chronic β-adrenergic stimulation. At baseline, the HG-KO mice had smaller hearts and the V-KO mice had larger hearts than their wild-type (WT) controls (P < .05). The HG-KO and their control WT mice had normal responses to TAC and β-adrenergic stimulation. However, the V-KO group was intolerant to TAC and had a significantly (P < .05) blunted response to β-adrenergic stimulation as compared with the HG-KO mice and WT controls. Unlike the HG-KO mice, the V-KO mice did not tolerate chronic isoproterenol infusion. Telemetric analysis of the electrocardiogram, body temperature, and activity revealed a normal diurnal rhythm in all groups of mice, but confirmed shorter QT intervals along with increased arrhythmias and reduced R wave to P wave amplitude ratios in the V-KO mice.Conclusions: Though NCX1 can be reduced by half in all myocytes without significant functional alterations, it must be expressed in more than 20% of the myocytes to prevent severe remodeling and heart failure in mouse heart.Myocardial Function With Reduced Expression of the Sodium-Calcium ExchangerMaria C. Jordan, Scott A. Henderson, Tieyan Han, Michael C. Fishbein, Kenneth D. Philipson, Kenneth P. Roos10.1016/j.cardfail.2010.03.012Journal of Cardiac Failure 16, 9 (2010)2010-05-14Journal of Cardiac Failure2010-05-14169S1071-9164(10)X0011-2Basic Science and Experimental Studies786796http://www.onlinejcf.com/article/PIIS1071916410010638/abstract?rss=yesCalendar of Events10.1016/S1071-9164(10)01063-8Journal of Cardiac Failure 16, 9 (2010)2010-09-01Journal of Cardiac Failure2010-09-01169S1071-9164(10)X0011-2Basic Science and Experimental Studies797797http://www.onlinejcf.com/article/PIIS1071916410010547/abstract?rss=yesEditorial Board10.1016/S1071-9164(10)01054-7Journal of Cardiac Failure 16, 9 (2010)2010-09-01Journal of Cardiac Failure2010-09-01169S1071-9164(10)X0011-2FrontmatterA3A3http://www.onlinejcf.com/article/PIIS1071916410010559/abstract?rss=yesMasthead10.1016/S1071-9164(10)01055-9Journal of Cardiac Failure 16, 9 (2010)2010-09-01Journal of Cardiac Failure2010-09-01169S1071-9164(10)X0011-2FrontmatterA4A4http://www.onlinejcf.com/article/PIIS1071916410010560/abstract?rss=yesTable of Contents10.1016/S1071-9164(10)01056-0Journal of Cardiac Failure 16, 9 (2010)2010-09-01Journal of Cardiac Failure2010-09-01169S1071-9164(10)X0011-2FrontmatterA5A6http://www.onlinejcf.com/article/PIIS1071916410010572/abstract?rss=yesInformation for Authors10.1016/S1071-9164(10)01057-2Journal of Cardiac Failure 16, 9 (2010)2010-09-01Journal of Cardiac Failure2010-09-01169S1071-9164(10)X0011-2FrontmatterA7A8