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JACC : Heart Failure    Follow    
  Full-text available via subscription Subscription journal
     ISSN (Online) 2213-1779
     Published by American College of Cardiology Foundation Homepage  [1 journal]
  • Meta-Analysis Bouillabaisse
    • Authors: O'Connor C.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Correction
    • Abstract: Sanderson JE. HFNEF, HFpEF, HF-PEF, or DHF: What Is an Acronym' J Am Coll Cardiol HF 2014;2:93–4.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Developing Therapies for Heart Failure With Preserved Ejection
           Fraction Current State and Future Directions
    • Authors: Butler J; Fonarow GC, Zile MR, et al.
      Abstract: The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • A Simplified Quantitative Evaluation of Right Ventricular Anatomy and
           Function by Intracardiac Echocardiography
    • Authors: Ren J; Callans DJ, Marchlinski FE.
      Abstract: We read with interest the report by Ujeyl et al. (1), which concluded that despite low left ventricular (LV) ejection fraction, patients with recurrent ventricular tachycardia (VT) who had good right ventricular (RV) function without elevated pulmonary artery systolic pressure (PASP) had a good prognosis after VT ablation, whereas RV dysfunction, tricuspid regurgitation (TR), and elevated PASP identified a high-risk group of VT survivors in whom additional interventions may be necessary to improve survival. Unfortunately, in the current study, no quantitative echocardiographic parameters of RV function and LV diastolic function were shown. In this retrospective study, RV dysfunction was dichotomized as 2 categories, no/mild and moderate/severe, on the basis of a qualitative description.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • How Can We Improve Inpatient Management of Heart Failure'
    • Authors: Dhamoon A; Liu K.
      Abstract: We read with great interest the report by Kociol et al. (1) on the association between inpatient hospitalist care of patients with heart failure and clinical outcomes. Their results suggest that utilization of the hospitalist model for patient care did not improve 30-day outcomes. Although comanagement by hospitalists and cardiologists may improve adherence to some quality measures, the findings of Kociol et al. also beg the following question: is there a novel diagnostic and management tool that frontline physicians can use to improve inpatient management of decompensated heart failure'
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Fatigue as a Predictor of Outcome in Patients With Heart Failure Analysis
           of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure)
    • Authors: Perez-Moreno A; Jhund PS, Macdonald MR, et al.
      Abstract: ObjectivesThe purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF) ≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study.BackgroundAlthough fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis.MethodsAt baseline in CORONA, fatigue “during the past few days” was measured using a 5-point exertion scale (0 = none, 1 = heavy exertion, 2 = moderate exertion, 3 = slight exertion, 4 = rest); a 4-point scale was used for dyspnea (1 to 4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n = 535), fatigue score 2 (n = 1,632), and fatigue score 3 to 4 (n = 1,663); and a dyspnea score of 1 (n = 292), dyspnea score of 2 (n = 1,695), and dyspnea score of 3 to 4 (n = 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality.ResultsIn univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n = 810], vs. group 1, 30% [n = 160]; dyspnea: group 3, 50% [n = 918], vs. group 1, 28% [n = 82]) and all-cause mortality (fatigue: group 3, 38% [n = 623], vs. group 1, 24% [n = 130]; dyspnea: group 3, 38% [n = 697], vs. group 1, 23% [n = 66], log-rank p < 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes.ConclusionsIn HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Anti-Inflammatory Treatment With Colchicine in Stable Chronic Heart
           Failure A Prospective, Randomized Study
    • Authors: Deftereos S; Giannopoulos G, Panagopoulou V, et al.
      Abstract: ObjectivesThe purpose of this study was to test the efficacy of a 6-month course of anti-inflammatory treatment with colchicine in improving functional status of patients with stable chronic heart failure (CHF).BackgroundCHF has been shown to be associated with inflammatory activation. Inflammation has been designated as a therapeutic target in CHF.MethodsPatients with stable CHF were randomly assigned to colchicine (0.5 mg twice daily) or placebo for 6 months. The primary endpoint was the proportion of patients achieving at least one-grade improvement in New York Heart Association class.ResultsTwo hundred sixty-seven patients were available for final evaluation of the primary endpoint: its rate was 11% in the control group and 14% in the colchicine group (odds ratio: 1.40; 95% confidence interval: 0.67 to 2.93; p = 0.365). The rate of the composite of death or hospital stay for heart failure was 9.4% in the control group, compared with 10.1% in the colchicine group (p = 0.839). The changes in treadmill exercise time with treatment were insignificant and similar in the 2 groups (p = 0.938). C-reactive protein and interleukin-6 were both significantly reduced in the colchicine group (–5.1 mg/l and –4.8 pg/ml, respectively; p < 0.001 for both, compared with the control group).ConclusionsAccording to this prospective, randomized study, anti-inflammatory treatment with colchicine in patients with stable CHF, although effective in reducing inflammation biomarker levels, did not affect in any significant way patient functional status (in terms of New York Heart Association class and objective treadmill exercise tolerance) or the likelihood of death or hospital stay for heart failure.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Randomized, Double-Blind, Placebo-Controlled Study of Sitaxsentan to
           Improve Impaired Exercise Tolerance in Patients With Heart Failure and a
           Preserved Ejection Fraction
    • Authors: Zile MR; Bourge RC, Redfield MM, et al.
      Abstract: ObjectivesThe purpose of this study was to evaluate the efficacy and safety of the selective endothelin type A (ETA) receptor antagonist sitaxsentan in patients who have heart failure with preserved ejection fraction (HFpEF).BackgroundFifty percent of heart failure (HF) patients have a preserved ejection fraction. No treatment has been shown to improve their clinical outcomes. Previous studies have suggested that ETA receptor antagonists might improve diastolic function and exercise tolerance in some forms of HF.MethodsIn all, 192 HFpEF patients (EF ≥50%) were randomly assigned 2:1 to sitaxsentan 100 mg/day (n = 128) versus placebo (n = 64) for 24 weeks. The primary endpoint was change in treadmill exercise time after 24 weeks of treatment. Secondary objectives included changes in left ventricular mass, transmitral inflow velocity to early diastolic mitral annulus velocity ratio, and Minnesota Living With Heart Failure questionnaire, and New York Heart Association functional class. Subjects were age 65 ± 11 years, 63% female, 29% non-Caucasian, and in functional class II (56.5%) or III (43.5%).ResultsSubjects treated with sitaxsentan had an increase in median treadmill time (90 s) compared with placebo-treated subjects (37 s, p = 0.0302). There was no significant treatment differences in transmitral inflow velocity to early diastolic mitral annulus velocity ratio, left ventricular mass, Minnesota Living With Heart Failure questionnaire, New York Heart Association functional class, deaths, or HF hospital stay. The incidence of adverse events was similar for sitaxsentan and placebo.ConclusionsIn HFpEF patients, treatment with a selective ETA receptor antagonist increased exercise tolerance but did not improve any of the secondary endpoints such as left ventricular mass or diastolic function. Further studies will be necessary to determine whether ETA receptor antagonists may be useful in the treatment of HFpEF. (A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure; NCT00303498)
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Inside This Issue
    • PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Left Ventricular Amyloid Deposition in Patients With Heart
           Failure and Preserved Ejection Fraction
    • Authors: Mohammed SF; Mirzoyev SA, Edwards WD, et al.
      Abstract: ObjectivesThis study sought to determine the frequency of left ventricular amyloid in heart failure with preserved ejection fraction (HFpEF).BackgroundLeft ventricular amyloid deposition can cause diastolic dysfunction and HFpEF.MethodsAutopsy of left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n = 109) and from control subjects (n = 131) were screened with sulfated Alcian blue and subsequent Congo red staining with microdissection for mass spectrometry–based proteomics to determine amyloid type. Fibrosis was assessed with quantitative whole-field digital microscopy.ResultsThe presence of wild-type transthyretin (wtTTR) amyloid was associated with age at death and male sex, but the age- and sex-adjusted prevalence of wtTTR amyloid was higher in HFpEF patients than in control subjects (odds ratio: 3.8, 95% confidence interval: 1.5 to 11.3; p = 0.03). Among HFpEF patients, moderate or severe interstitial wtTTR deposition, consistent with senile systemic amyloidosis as the primary etiology of HFpEF, was present in 5 (5%) patients (80% men), with mild interstitial and/or variable severity of intramural coronary vascular deposition in 13 (12%) patients. While, wtTTR deposition was often mild, adjusting for age and presence of HFpEF, wtTTR amyloid was associated with more fibrosis (p = 0.005) and lower age, sex, and body size–adjusted heart weight (p = 0.04).ConclusionsGiven the age- and sex-independent association of HFpEF and wtTTR deposition and an emerging understanding of the pathophysiology of the amyloidoses, the current findings support further investigation of the role of wtTTR in the pathophysiology of HFpEF.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Time for Change in United States Donor Heart Allocation Policy ∗
    • Authors: Kobashigawa JA.
      Abstract: In this issue of JACC: Heat Failure, Schulze et al. (1) report on the impact of the 2006 United Network for Organ Sharing (UNOS) donor heart allocation policy change on patients waiting for heart transplant and post-transplant patient outcomes in the United States. This policy change allocated donor hearts to the most sick patients (status 1A/1B) first locally, then to Zone A (500-mile radius from the donor hospital), then to Zone B (1,000-mile radius), with the goal to reduce waitlist mortality. Importantly, the authors demonstrated a reduction in waitlist and post-transplant mortalities while illustrating differences in regional waitlist time and mechanical circulatory support device (MCSD) use after the policy change. The authors also noted an overall increase in average waitlist times since the 2006 policy was implemented. The authors conclude that the 2006 policy change and the recent greater use of MCSDs both contributed to the reduction of waitlist and post-transplant mortalities. In addition, presumably due to the longer waitlist times, the use of MCSDs increased more dramatically in several regions. The authors raise concern that the longer waitlist time might result in more MCSD complications that could lead to worsening post-transplant outcome in the future.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Effects of Exercise Training on Outcomes in Women With Heart Failure
           Analysis of HF-ACTION (Heart Failure–A Controlled
           Trial Investigating Outcomes of Exercise TraiNing) by Sex
    • Authors: Piña IL; Bittner V, Clare RM, et al.
      Abstract: ObjectivesThe authors hypothesized that the women enrolled in the HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial and randomly assigned to exercise training (ET) would improve functional capacity as measured by peak oxygen uptake (VO2) compared with those in the usual care group. Furthermore, they hypothesized that the improvement in peak VO2 would correlate with prognosis. They explored whether exercise had a differential effect on outcomes in women versus men.BackgroundThere is less evidence for the benefit of ET in women with heart failure (HF) compared with men because of the small numbers of women studied.MethodsHF-ACTION was a randomized trial of ET versus usual care in 2,331 patients with class II-IV HF and a left ventricular ejection fraction of ≤35%. Sex differences in the effects of randomized treatment on clinical outcomes were assessed through the use of a series of Cox proportional hazards models, controlling for covariates known to affect prognosis in HF-ACTION.ResultsWomen had lower baseline peak VO2 and 6-min walk distance than did men (median, 13.4 vs. 14.9 ml/min/kg and 353 vs. 378 m, respectively). An increase in peak VO2 at 3 months was present in women and men in the ET group (mean ± SD; median, 0.88 ± 2.2, 0.80 and 0.77 ± 2.7, 0.60, respectively, women vs. men; p = 0.42). Women randomly assigned to ET had a significant reduction in the primary endpoint, (hazard ratio: 0.74) compared with men (hazard ratio: 0.99) randomly assigned to ET, with a significant treatment-by-sex interaction (p = 0.027).ConclusionsAlthough there is no significant difference between men and women in the effect of ET on peak VO2 change at 3 months, ET in women with HF is associated with a larger reduction in rate of the combined endpoint of all-cause mortality and hospital stay than in men.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Impact of Cardiovascular Events on Change in Quality of Life and Utilities
           in Patients After Myocardial Infarction A VALIANT Study (Valsartan In
           Acute Myocardial Infarction)
    • Authors: Lewis EF; Li Y, Pfeffer MA, et al.
      Abstract: ObjectivesThe objective of this study was to determine the impact of nonfatal cardiovascular (CV) events on changes in health-related quality of life (HRQL).BackgroundThere is limited understanding of the impact of nonfatal CV events on long-term changes in HRQL in survivors of myocardial infarction (MI).MethodsThe VALIANT (Valsartan In Acute Myocardial Infarction) trial enrolled 14,703 patients post-MI complicated by Killip class II or higher (scale measuring heart failure severity post-MI ranging from class I to IV) and/or reduced ejection fraction. The HRQL substudy included 2,556 (17.4%) patients who completed the EQ-5D with 5 questions, with responses mapped to utility weight on a scale of 0 to 1 and a visual analog scale (VAS) ranging from 0 (worst) to 100 (best) imaginable health state. EQ-5D was administered at baseline and 6, 12, 20, and 24 months. The trajectory of EQ-5D scores was developed by using linear mixed effects regression models with calculation of deviation from this trajectory after nonfatal CV events. Patients who died before the next EQ-5D assessment were excluded.ResultsOver a 2-year period, 597 patients experienced a nonfatal CV event and survived to have another EQ-5D assessment. Their baseline EQ-5D scores were lower than patients without a subsequent nonfatal CV event (VAS 61.0 ± 19 vs 68.2 ± 18 [p < 0.001] and US-based utility score 0.76 ± 0.22 vs 0.83 ± 0.17 [p < 0.001]). These patients with CV events experienced a trajectory-adjusted 6.6 point decrease (p < 0.001) in VAS scores and a 0.07 decrease (p 
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Regional Differences in Recipient Waitlist Time and Pre- and
           Post-Transplant Mortality After the 2006 United Network for
    • Authors: Schulze P; Kitada S, Clerkin K, et al.
      Abstract: ObjectivesThis study examined the impact of the United Network for Organ Sharing (UNOS) policy changes for regional differences in waitlist time and mortality before and after heart transplantation.BackgroundThe 2006 UNOS thoracic organ allocation policy change was implemented to allow for greater regional sharing of organs for heart transplantation.MethodsWe analyzed 36,789 patients who were listed for heart transplantation from January 1999 through April 2012. These patients were separated into 2 eras centered on the July 12, 2006 UNOS policy change. Pre- and post-transplantation characteristics were compared by UNOS regions.ResultsWaitlist mortality decreased nationally (up to 180 days: 13.3% vs. 7.9% after the UNOS policy change, p < 0.001) and within each region. Similarly, 2-year post-transplant mortality decreased nationally (2-year mortality: 17.3% vs. 14.6%; p < 0.001) as well as regionally. Waitlist time for UNOS status 1A and 1B candidates increased nationally 17.8 days on average (p < 0.001) with variability between the regions. The greatest increases were in Region 9 (59.2-day increase, p < 0.001) and Region 4 (41.2-day increase, p < 0.001). Although the use of mechanical circulatory support increased nearly 2.3-fold nationally in Era 2, significant differences were present on a regional basis. In Regions 6, 7, and 10, nearly 40% of those transplanted required left ventricular assist device bridging, whereas only 19.6%, 22.3%, and 15.5% required a left ventricular assist device in regions 3, 4, and 5, respectively.ConclusionsThe 2006 UNOS policy change has resulted in significant regional heterogeneity with respect to waitlist time and reliance on mechanical circulatory support as a bridge to transplantation, although overall both waitlist mortality and post-transplant survival are improved.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Changes of Natriuretic Peptides Predict Hospital Admissions in Patients
           With Chronic Heart Failure A Meta-Analysis
    • Authors: Savarese G; Musella F, D’Amore C, et al.
      Abstract: ObjectivesThe goal of this study was to explore the association between changes in B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) plasma levels and risk of hospital admission for heart failure (HF) worsening in patients with chronic HF.BackgroundThe relationship between BNP and NT-proBNP plasma levels and risk of cardiovascular events in patients with chronic HF has been previously demonstrated. However, it is unclear whether changes in BNP and NT-proBNP levels predict morbidity in patients with chronic HF.MethodsThe MEDLINE, Cochrane, ISI Web of Science, and SCOPUS databases were searched for papers about HF treatment up to August 2013. Randomized trials enrolling patients with systolic HF, assessing BNP and/or NT-proBNP at baseline and at end of follow-up, and reporting hospital stay for HF were included in the analysis. Meta-regression analysis was performed to test the relationship between BNP and NT-proBNP changes and the clinical endpoint. Sensitivity analysis was performed to assess the influence of baseline variables on results. Egger's linear regression was used to assess publication bias.ResultsNineteen trials enrolling 12,891 participants were included. The median follow-up was 9.5 months (interquartile range: 6 to 18 months), and 22% of patients were women. Active treatments significantly reduced the risk of hospital stay for HF worsening. In meta-regression analysis, changes in BNP and NT-proBNP were significantly associated with risk of hospital stay for HF worsening. Results were confirmed by using sensitivity analysis. No publication bias was detected.ConclusionsIn patients with HF, reduction of BNP or NT-proBNP levels was associated with reduced risk of hospital stay for HF worsening.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Acquired von Willebrand Syndrome in Patients With a Centrifugal or Axial
           Continuous Flow Left Ventricular Assist Device
    • Authors: Meyer AL; Malehsa D, Budde U, et al.
      Abstract: ObjectivesThe aim of this study was to determine whether differences in continuous flow left ventricular assist devices (LVADs) may lead to differences in the von Willebrand profile and the occurrence of bleeding and thromboembolic events.BackgroundThe HeartMate II (Thoratec Corp., Pleasanton, California) and HeartWare Ventricular Assist Device (HVAD) (HeartWare, Inc., Framingham, Massachusetts) systems are the most frequently implanted LVADs worldwide. In all patients with an axial-flow HeartMate II, acquired von Willebrand syndrome (AvWS) due to the loss of large molecular weight multimers was found. The large molecular weight multimers of the von Willebrand factor (vWF) play a key role in primary hemostasis through interactions with platelets.MethodsThis was a retrospective study of the vWF profile and incidence of bleeding and thromboembolic events in 102 patients receiving the HeartMate II (n = 51) and HVAD (n = 51). Between January 2003 and December 2010, vWF testing was performed in 102 of 175 consecutive patients after LVAD implantation.ResultsAvWS was found in all patients, demonstrated by a decrease in the high molecular weight multimers of vWF to 30 ± 14% in HeartMate II patients and 34 ± 13% in patients with an HVAD. Significant predictors of vWF antigen included age (p = 0.011), number of days on the device (p = 0.035), C-reactive protein (p < 0.001), and blood group (p = 0.007). Bleeding and thromboembolic event rates were similar. However, lower fractions of vWF antigen and high molecular weight multimers did not correlate with the rate of bleeding complications or thromboembolic events.ConclusionsAvWS developed in all patients after centrifugal or axial flow pump implantation. Different patterns of AvWS were seen between the devices as well as individually. However, the complication rates after implantation were similar.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Are Centrifugal Ventricular Assist Devices the Answer to Reducing
           Post-Implantation Gastrointestinal Bleeding' ∗
    • Authors: Crow SS; Joyce DD.
      Abstract: Ventricular assist devices (VAD) are an effective and innovative strategy for prolonging the life of patients with end-stage congestive heart failure. However, significant rates of post-implantation nonsurgical bleeding continue to challenge the management of these patients (1). Over the last 15 years, VADs have transitioned from early pulsatile models to present-day nonpulsatile continuous-flow designs such as the axial HeartMate II (HM II) (Thoratec Corporation, Pleasanton, California) and centrifugal HeartWare (HVAD) (HeartWare Inc., Framingham, Massachusetts). Initial investigations demonstrated that pulsatile and nonpulsatile VADs had comparable outcomes with equivalent risk profiles (2). However, longer-term follow-up revealed that the newer generation nonpulsatile VAD recipients experienced a higher rate of gastrointestinal (GI) bleeding than their pulsatile predecessors (1). Despite these findings, the continuous-flow VAD is now the implant of choice due to its smaller size and long-term durability. The primary source of nonsurgical bleeding in continuous-flow VAD recipients is from the GI tract and nasal mucosa. Patients with severe aortic stenosis demonstrate a similar bleeding pattern, and the associated disruption in von Willebrand factor (vWF) protein is now known as acquired von Willebrand syndrome (3). vWF is a 250 kDa protein synthesized by endothelial cells and megakaryocytes that circulates in the blood in a globular form. Blood flow through areas of high sheer stress causes an unfolding of the vWF protein, exposing sites for proteolysis and cleavage by the enzyme ADAMTS 13 (4). ADAMTS 13 cleavage divides the vWF protein into smaller segments or multimers. Following this process, the total amount of vWF in circulation remains unchanged but the number of large vWF pieces known as high molecular weight multimers (HMWM) are decreased (5). Clinically, HMWM loss is associated with bleeding secondary to the decreased ability of vWF to bind collagen and platelets to achieve hemostasis. The calcific aortic valve in aortic stenosis and the VAD impeller in a heart failure patient are believed to create an environment of high shear stress that induces vWF unfolding, cleavage, and ultimately HMWM loss. Loss of HMWM following implantation of axial continuous-flow VAD has been well demonstrated (6,77).
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
  • Colchicine and the Failing Heart A “FINER” Anti-Inflammatory
           Agent' ∗
    • Authors: Mann DL.
      Abstract: Ever since the original description of proinflammatory cytokines in patients with heart failure in 1990 (1), there has been enormous interest in the role that these molecules play in regulating cardiac structure and function, particularly with regard to their potential role in disease progression in heart failure. The recognition of the important pathophysiological consequences of sustained expression of proinflammatory mediators in pre-clinical and clinical heart failure models culminated in a series of multicenter clinical trials that utilized “targeted” approaches to neutralize tumor necrosis factor in patients with moderate to advanced heart failure. Unfortunately, these targeted approaches were negative with respect to the primary endpoints of the trial and, in some patients, resulted in worsening heart failure and/or death (2,33). Collectively, these 2 clinical trials have had a chilling effect on further attempts to target inflammation in heart failure, and have raised a number of nagging questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. Germane to the present discussion, in this issue of JACC: Heart Failure, Deftereos et al. (4) report their findings on a 6-month course of treatment with colchicine in patients with heart failure with a depressed ejection fraction ≤40%. The rationale for this study was that colchicine has been known to exert anti-inflammatory effects in various cardiovascular settings (5), and might therefore also be useful in treating heart failure patients. Patients with stable heart failure on appropriate medical therapy were randomized to receive colchicine (0.5 mg twice daily) or placebo for 6 months. The primary endpoint of the study, for which the trial was powered adequately, was the proportion of patients achieving at least a 1-grade improvement in New York Heart Association functional class. Secondary endpoints, for which the trial was not adequately powered for, included a composite of death and hospital stay for heart failure, the change in left ventricular and end-diastolic diameter (2-dimensional echocardiography), change in left ventricular ejection fraction, and change in treadmill exercise time. In comparison to patients who were treated with conventional heart failure therapy, the authors observed that 11% of the control subjects had an improvement in New York Heart Association functional class, whereas 14% of patients in the colchicine group experienced an improvement in New York Heart Association functional classification (p = 0.36). Moreover, the composite of death or hospital stay for heart failure was 9.4% in the control group compared with 10.1% in the colchicine group (p = 0.84). The changes in treadmill exercise time were insignificant in the control group and treatment arms. Importantly, the magnitude of the decrease in circulating levels of C-reactive protein (CRP) and interleukin (IL)-6 were both significantly reduced in the colchicine-treated group when compared with placebo. There was an approximately 2-fold increase (p = 0.007) in gastrointestinal symptoms in the treatment group, whereas there were no serious complications in terms of renal and/or hepatic function. The authors conclude that anti-inflammatory treatment with colchicine in patients with stable heart failure, although effective in reducing inflammation biomarker levels, did not significantly affect functional class or the likelihood of death or hospital stay. Given the negative outcome of previous trials using anti-inflammatory agents in heart failure, the current study raises further questions about targeting of inflammation in this patient population.
      PubDate: Tue, 01 Apr 2014 00:00:00 GMT
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