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 Table of Contents  
CARDIOLOGY UPDATE
Year : 2015  |  Volume : 1  |  Issue : 2  |  Page : 206-211

Heart failure report


1 Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Cardiology, Care Hospitals, Hyderabad, Telangana, India

Date of Web Publication30-Sep-2015

Correspondence Address:
Dr. Himanshu Meghwani B. K. S Sastry
Care Hospitals, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2395-5414.166343

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  Abstract 

Despite advancements in diagnosis and pharmacotherapy, heart failure (HF) remains as a major health problem. The prevalence in the general population is estimated to range from 0.3% to 2.0%, increases considerably with age, and approximately doubles with every additional decade of life. In the last two decades, hospital admission rates for HF have increased steadily. The prevalence of HF can be estimated at 1–2% in the Western world and the incidence approaches 5–10/1000 persons/year. Estimates of the occurrence of HF in the developing world are largely absent. In a recent US population-based study, the prevalence of HF was 2.2% (95 confidence interval 1.6–2.8%), increasing from 0.7% in persons aged 45 through 54 years to 8.4% for those aged 75 years or older. In this article, we look at the major papers published in HF in the past 1 year.

Keywords: Heart failure, review, 2015


How to cite this article:
Dua P, Sastry HB. Heart failure report. J Pract Cardiovasc Sci 2015;1:206-11

How to cite this URL:
Dua P, Sastry HB. Heart failure report. J Pract Cardiovasc Sci [serial online] 2015 [cited 2019 Oct 20];1:206-11. Available from: http://www.j-pcs.org/text.asp?2015/1/2/206/166343


  Introduction Top


Heart failure prevalence is rising, and only small improvement in survival is occurring. Promising new therapies being tested include an angiotensin receptor- neprilysin inhibitor, a naturally-occurring vasodilator peptide, a myofilament sensitizer and several drugs that enhance Ca++ uptake by the sarcoplasmic reticulum. Cell therapy, using autologous bone marrow and cardiac progenitor cells is also being tested. Chronic left ventricular assistance with continuous flow pumps is being applied successfully as destination therapy, as a bridge to transplantation, and even as a bridge to recovery and explantation. Some of these have, in the past one year, shown success in clinical trials and are reviewed below.[1],[2],[3],[4]

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004[5]

Angiotensin-converting enzyme inhibitor (ACEI) therapy reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF). Neprilysin is an endopeptidase that breaks down vasoactive peptides (brain natriuretic peptide [BNP], bradykinin, and adrenomedullin); its inhibition may, therefore, reduce remodeling, vasoconstriction, renal sodium retention, and improve outcomes in HFrEF. The OVERTURE trial found that use of omapatrilat (an agent that inhibits ACE, aminopeptidase P, and neprilysin) reduced mortality and hospitalization when compared to ACEI use. Omapatrilat was associated with a higher rate of angioedema. Use of a neprilysin inhibitor plus an angiotensin receptor blocker (ARB) (angiotensin receptor neprilysin inhibitor [ARNI]) may provide benefit over ACEI monotherapy in the treatment of HFrEF without increasing the rates of angioedema. The experimental ARNI named LCZ696 combined an ARB (valsartan 160 mg) with a neprilysin inhibitor (sacubitril).

The prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in HF trial randomized 8399 patients with HFrEF (left ventricular ejection fraction [LVEF] ≥40% and ≥35% were used at different points in the trial) and New York Heart Association (NYHA) Class II–IV symptoms to the ARNI LCZ696 (sacubitril) 200 mg p.o. BID or enalapril 10 mg p.o. BID. With a median follow-up of 27 months, the trial was stopped following a positive efficacy analysis. The ARNI group had a reduction in the primary outcome of cardiovascular (CV) mortality or HF hospitalization. The ARNI had a significant reduction in all-cause mortality (17.0% vs. 19.8%). The ARNI was generally well tolerated except for a higher rate of symptomatic hypotension, though not to an increased rate of discontinuation of the therapy due to hypotension. There was no difference in the rates of angioedema. The Food and Drug Administration approved the valsartan/sacubitril combination pill in July 2015.

Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, et al. Efficacy of ß blockers in patients with heart failure plus atrial fibrillation: An individual patient data meta-analysis. Lancet 2014;384:2235-43[6]

The efficacy of β-blockers in patients with concomitant atrial fibrillation (AF) is uncertain. Kotecha et al. tried to explore this fact through a meta-analysis. In this study, data from 10 randomized controlled trials (RCTs) of the comparison of β-blockers versus placebo in HF were collected. Sinus rhythm or AF was ascertained from the baseline electrocardiography and all-cause mortality was the primary outcome measure based on intention to treat analysis. Outcome data were meta-analyzed with an adjusted Cox proportional hazards regression.

Thirteen thousand nine hundred forty-six (76%) had sinus rhythm and 3066 (17%) had AF out of 18,254 patients at baseline. Crude death rates over a mean follow-up of 1.5 years (standard deviation [SD] 1.1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with AF. There was a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio [HR] 0.73, 0.67–0.80; P < 0.001), but not in patients with AF (0.97, 0.83–1.14; P = 0.73), with a significant P value for interaction of baseline rhythm (P = 0.002) with β-blocker therapy. The lack of efficacy for the primary outcome was noted in all subgroups of AF, including age, sex, LVEF, NYHA class, heart rate, and baseline medical therapy. The study concluded the lack of effect of β-blockers in patients of HF plus AF.

Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014;370:1383-92[7]

Mineral-corticoid-receptor antagonist, e.g., spironolactone improves the patients with HF and a reduced LVEF. Pitt et al. designed a double-blind study to assess the efficacy of spironolactone, in which 3445 patients with symptomatic HF and an LVEF of ≥45% were randomized into two groups to either spironolactone (15–45 mg daily) or placebo. Mortality from CV causes, aborted cardiac arrest, or hospitalization during HF management were the primary outcome measures.

Mean follow-up was for 3.3 years, primary outcome in the spironolactone group was 18.6% and in the placebo group it was 20.4% (P = 0.14). Significantly, lower incidence of hospitalization was there in the spironolactone group (12.0%) than in the placebo group (14.2%), P = 0.04. Total deaths and all-cause hospitalizations were same in both groups. Serum creatinine levels (18.7%) and hyperkalemia (9.1%) was raised in spironolactone group than in placebo group, but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events. Hence, spironolactone did not significantly reduce the incidence of the primary composite outcome of death from CV causes, aborted cardiac arrest, or hospitalization for the management of heart failure with preserved ejection fraction.

Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, et al. Survival with cardiac resynchronization therapy in mild heart failure. N Engl J Med 2014;370:1694-701[8]

In this study, the effect of cardiac resynchronization therapy-defibrillator (CRT-D) on long-term survival in the Multicenter Automatic Defibrillator Implantation-CRT population was evaluated. Posttrial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (Phase 1) and subsequently among 854 patients who were enrolled in posttrial registries (Phase 2). At 7 years of follow-up after initial enrollment, the cumulative rate of death in patients with Left bundle-branch block (LBBB) was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone. The long-term survival benefit of CRT-D in patients with LBBB was not significantly different according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without LBBB. In patients with mild HF symptoms, left ventricular dysfunction, and LBBB, early intervention with CRT-D was associated with a significant long-term survival benefit.

Hindricks G, Taborsky M, Glikson M, Heinrich U, Schumacher B, Katz A, et al. Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): A randomized controlled trial. Lancet 2014;384:583-90[9]

Implant-based telemonitoring might enable preemptive intervention and improve outcomes of failing heart. With this aim, this RCT was done by Hindricks et al. in 36 tertiary centers. A total of 664 patients with chronic HF, NYHA Class II–III, EF <35% of optimal drug treatment and no AF, and a recent dual-chamber implantable cardioverter defibrillator (ICD) or CRT-D implantation were recruited. One group was with automatic, daily, implant-based, multiparameter telemonitoring (333 patients) in addition to standard care and the second one was with standard care without telemonitoring (331 patients), with 1 year follow-up. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for HF, change in NYHA class, and change in patient global self-assessment. In 1 year of follow-up, 18.9% patients in the telemonitoring group and 27.2% in the control group (P = 0·013) had worsened composite score (odds ratio [OR] 0·63). Ten patients in the telemonitoring group and 27 patients in the control group were died during follow-up. Hence, the automatic, daily, implant-based, multiparameter telemonitoring can significantly improve the clinical outcomes for patients with HF. Such telemonitoring is feasible and should be used in the clinical practice. In summary, new ICDs and CRT-Ds having telemonitoring functions and technical and physiological information were recorded by the device, sent this information to a clinical monitoring team via a mobile telephone link and significantly improved outcomes were compared with an unmonitored control group.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients. 35thAnnual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT 2015) in Nice, France; April 17, 2015[10]

A comparative study of left ventricular assist device (LVAD) supported patients and patients with standard care was done. One hundred and three patients received guideline-optimized medical therapy and 97 received the LVAD as destination therapy. The primary end point was: A composite end point that included survival at 12 months and an increase in the 6-min-walk test of at least 75 meters. Functionally-limited HF patients who received LVAD as destination therapy had significantly improved survival and functional status at 12 months when compared with similar patients treated with optimal medical therapy alone. Patients supported by LVADs had a greater improvement in quality of life and a greater improvement in the severity of their depression. Survival at 12 months and an increase in the 6-min-walk test of at least 75 m were occurred in 39% of patients treated with LVAD and 21% of those who received optimal medical therapy (P = 0.017). Overall, the adverse event rate was less in the medical management arm including an increased risk of ischemic stroke.

Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency† . Eur Heart J 2015;36:657-68[11]

Evaluation of the benefits and safety of long-term intravenous (IV) iron therapy in iron-deficient patients with HF was done in this study. This trial enrolled 304 patients with NYHA Class II–III HF, LVEF <45%, elevated BNP, and serum ferritin <100 ng/ml or 100 to 300 ng/ml, if transferrin saturation was <20%. Patients were randomized 1:1 to IV ferric carboxymaltose or placebo given at baseline, 6, 12, 24, and 36 weeks. At 24th week, patients in the iron-supplementation arm had improved their 6-min-walk test, the trial's primary endpoint by a mean of 33 m compared with placebo-treated patients. That difference was sustained out to 1 year. Significant improvements were also seen in NYHA class, patient global assessment, quality of life, and fatigue score.

Cohen-Solal A, Damy T, Hanon O, Terbah M, Laperche T, Kerebel S, et al. High prevalence of iron deficiency in patients admitted for acute decompensated heart failure: A French study (CARDIOFER). J Am Coll Cardiol 2014;63[12]

Iron deficiency (ID) may be frequent in patients with chronic HF and can be improved with IV iron therapy; however, few data are available on ID status in acute decompensated HF (ADHF). Methods: Cardiofer is a multicenter, clinical study conducted at 46 sites in patients hospitalized for ADHF. ID (assessed in the first 72 h postadmission) was defined according to the European Society of Cardiology Guidelines for 2012 as a serum ferritin <100 µg/L (absolute ID) or a serum ferritin between 100 and 299 µg/L with transferrin saturation <20% (function ID). Anemia was defined as hemoglobin concentration <13 g/dl in men and <12 g/dl in women. Four hundred eleven men (74.8 ± 12.0 years) and 421 women (81.2 ± 11.4 years) were evaluated. In that evaluation, the prevalence of anemia was 67.6% in men and 52.0% in women, and that of ID was 68.6% in men and 75.3% in women. Absolute ID (serum ferritin <100 µg/L) was the most common type of ID, with a prevalence of 40.6% in men and 48.9% in women. In patients without anemia, ID prevalence was 57.1% in men and 78.7% in women. There was no significant relationship in either men or women between anemia or ID status with age, NYHA class, BNP, or LVEF. ID is very common in patients admitted for ADHF, even in patients without anemia. ID before ADHF is underdiagnosed and undertreated.

Dunlay SM, Manemann SM, Chamberlain AM, Cheville AL, Jiang R, Weston SA, et al. Activities of daily living and outcomes in heart failure. Circ Heart Fail 2015;8:261-7[13]

Chronic disease can contribute to functional disability, which can degrade the quality of life. However, the prevalence of functional disability and its association with outcomes among patients with HF requires further study. Southeastern Minnesota residents with HF were enrolled from September 2003 to January 2012 in a cohort study with follow-up through December 2012. Difficulty with nine activities of daily living (ADLs) was assessed by a questionnaire. Patients were divided into three categories of ADL difficulty (no/minimal, moderate, and severe). The associations of ADL difficulty with mortality and hospitalization were assessed using Cox and Andersen–Gill models. Among 1128 patients (mean age, 74.7 years; 49.2% female), majority (59.4%) reported difficulty with one or more ADLs at enrollment, with 272 (24.1%) and 146 patients (12.9%) were experiencing moderate and severe difficulty, respectively. After a mean (SD) follow-up of 3.2 (2.4) years, 614 patients (54.4%) had died. Mortality increased with increasing ADL difficulty; the HR (95% confidence interval [CI]) for death was 1.49 (1.22–1.82) and 2.26 (1.79–2.86) for those with moderate and severe difficulty, respectively, compared to those with no/minimal difficulty (P < 0.001). The patients with moderate and severe difficulty were at an increased risk for all-cause and no CV hospitalization, respectively. In a second assessment, 17.7% of survivors reported more difficulty with ADLs and patients with persistently severe or worsening difficulty were at an increased risk for death (HR, 2.10; 95% CI, 1.71–2.58; P < 0.001) and hospitalization (HR, 1.51; 95% CI, 1.31–1.74; P < 0.001). Hence, functional disability is common in patients with HF, can progress over time, and is associated with adverse prognosis.

Chahal H, Bluemke DA, Wu CO, McClelland R, Liu K, Shea SJ, et al. Heart failure risk prediction in the Multi-Ethnic Study of Atherosclerosis. Heart 2015;101:58-64[14]

HF is a leading cause of mortality, especially in older populations. Early detection of high-risk individuals is imperative for primary prevention. The purpose of this study was to develop a HF risk model from a population without clinical cardiac disease. The multi-ethnic study of atherosclerosis is a multicenter observational cohort study following 6814 subjects (mean age 62 ± 10 years; 47% men) who were free of clinical CV disease at baseline. Median follow-up was 4.7 years. HF events were developed in 176 participants. Cox proportional hazards models and regression coefficients were used to determine independent risk factors and generate a 5-year risk score for incident HF. Bootstrapping with bias correction was used for internal validation. According to the results, independent predictors for HF (HR, P value) were age (1.30 [1.10–1.50]/10 years), male gender (2.27 [1.53–3.36]), current smoking (1.97 [1.15–3.36]), body mass index (1.40 [1.10–1.80]/5 kg/m 2), systolic blood pressure (1.10 [1.00–1.10]/10 mmHg), heart rate (1.30 [1.10–1.40]/10 bpm), diabetes (2.27 [1.48–3.47]), N-terminal pro-B-type natriuretic peptide (NT proBNP) (2.48 [2.16 to 2.84]/unit log increment), and left ventricular mass index (1.40 [1.30–1.40]/10 g/m 2). A parsimonious model based on age, gender, body mass index, smoking status, systolic blood pressure, heart rate, diabetes, and NT proBNP natriuretic peptide predicted incident HF risk with a C-statistic of 0.87. A clinical algorithm based on risk factors readily available in the primary care setting can be used to identify individuals with a high likelihood of developing HF without preexisting cardiac disease.

Pasternak B, Svanström H, Melbye M, Hviid A. Association of treatment with carvedilol vs metoprolol succinate and mortality in patients with heart failure. JAMA Intern Med 2014;174:1597-604[15]

The study was to investigate whether carvedilol is associated with improved survival compared with metoprolol succinate. Cohort study of patients with incident HF and with reduced LVEF (≤40%) who received carvedilol (n = 6026) or metoprolol succinate (n = 5638) using data from a Danish national HF registry was linked with health care and administrative databases.

All-cause mortality (primary outcome) and CV mortality (secondary outcome) were analyzed using Cox regression with adjustment for a propensity score, derived from a range of clinical, socioeconomic, and demographic characteristics. The mean (SD) age of the patients was 69.3 (9.1) years, 71% were men, and 51% were hospitalized at index HF diagnosis. During a median (inter-quartile range) 2.4 (1.0–3.0) years of follow-up, 875 carvedilol users and 754 metoprolol users were died; the cumulative incidence of mortality was 18.3% and 18.8%, respectively. The adjusted HR for carvedilol users versus metoprolol users was 0.99 (95% CI, 0.88–1.11), corresponding to an absolute risk difference of − 0.07 (95% CI, −0.84 to 0.77) deaths/100 person-years. Estimates were consistent across subgroup analyses by sex, age, levels of LVEF, and NYHA.

A higher proportion of carvedilol users achieved the recommended daily target dose (50 mg; 3124 [52%]) than did metoprolol users (200 mg; 689 [12%]). The adjusted HR for CV mortality was 1.05 (95% CI, 0.88–1.26). In this study, the effectiveness of carvedilol and metoprolol succinate in patients with HF was similar.

Kurt P, John N, John T, Peter E, Sue D. Effects of beta-blocker withdrawal in patients admitted with acute decompensate heart failure: A systematic review and meta-analysis. J Am Coll Cardiol 2015;65:s0735-1097[16]

Five observational studies and one randomized clinical trial (n = 2704 patients who continued β-blocker therapy and n = 439 patients who discontinued β-blocker therapy) that reported the short-term effects of β-blocker withdrawal in ADHF were included in the analyses. In two studies, β-blocker withdrawal significantly increased the risk of in-hospital mortality (OR: 3.73 [95% CI: 1.51–9.19]). Short-term mortality (OR 1.71 [95% CI: 1.09–2.68]; four studies) and combined short-term re-hospitalization and/or death (OR 2.16 [95% CI: 1.01–4.61]; four studies) were also significantly increased. Discontinuation of β-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined end point of short-term re-hospitalization and/or mortality rates. These data suggest β-blockers should be continued in all ADHF patients, if their clinical picture allows.

Bayar N, Küçükseymen S, Göktas S, Arslan S. Right ventricle failure associated with trastuzumab. Ther Adv Drug Saf 2015;6:98-102[17]

Trastuzumab (TZ), a monoclonal antibody against human epidermal growth factor receptor type 2, is an important biological agent used for the treatment of positive breast cancer. This paper presents a 46-year-old female patient who developed right HF and right ventricular (RV) dysfunction while on TZ due to breast cancer, and returned to normal following the discontinuation of the drug. As far as we know, this is the first case report related to a patient presenting with RV dysfunction and induced cardiotoxicity while on TZ.

Kayvanpour E, Mansi T, Sedaghat-Hamedani F, Amr A, Neumann D, Georgescu B, et al. Towards personalized cardiology: Multi-scale modeling of the failing heart. PLoS One 2015;10:e0134869[18]

Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of nonresponders. State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics, and hemodynamics was estimated using a robust framework. The model was computed on n = 46 HF patients, showing for the 1st time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests, and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters.

This paper illustrates how advanced multi-scale models can complement CV imaging and how they could be applied in patient care. Based on the obtained results, it becomes conceivable that after thorough validation such HF models could be applied for patient management and therapy planning in the future.

As an example of application for personalized therapy, the authors simulated CRT using a virtual heart in 1 patient of the cohort. The model was able to successfully, highly, and accurately predict the changes for different CRT stimulation protocols. It was able to predict the worsening of cardiac electrophysiology for both bi-ventricular (BiV) and RV pacing modes. The later protocol was chosen by the independent treating electrophysiologist, and the patient after device implantation showed a significant improvement of clinical symptoms as well as LV-EF.

Buggey J, Mentz RJ, DeVore AD, Velazquez EJ. Angiotensin receptor neprilysin inhibition in heart failure: Mechanistic action and clinical impact. J Card Fail 2015;21:741-50[19]

HF is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity of new pharmacotherapies that improve outcomes over the past decade. However, recent data from a large, RCT compared the novel agent LCZ696, a dual acting ARB and ARNI to the well-established ACEI enalapril and found significant reduction in mortality among the chronic, reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides thereby promoting natriuresis, vasodilatation, and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACEI, but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNI LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, the preclinical and clinical data were reviewed that has led to the development of LCZ696 and the understanding of the underlying mechanistic action and the robust clinical impact that LCZ696 may have in the near future.

Enciu EC, Stanciu SM, Matei D, Costache A. Prognostic markers in the pathology of cardiac failure: Echocardiography and autonomic nervous system dysfunction. Rom J Morphol Embryol 2015;56:401-6[20]

Chronic HF is a major health problem worldwide and despite the therapeutic advances, the mortality and morbidity still remain high. Echocardiography is the gold standard for left ventricular function assessment. Another parameter is studied, recently recognized as a marker for future cardiac events: Autonomic nervous dysfunction. The current paper makes a comprehensive approach of the echocardiographic markers recommended for the diagnosis and follow-up of HF. Tissue Doppler imaging and heart rate recovery are recommended as new parameters to be measured.

Janoušek J, Kovalev IA, Kubuš P, Chernyshev AA, Krivoshchekov EV, Krivolapov SN, et al. Cardiac resynchronization therapy in the treatment of heart failure in children. Kardiologiia 2015;55:87-95[21]

CRT is currently a leading approach to the treatment of HF in adults. However, data regarding the application of CRT in children remain limited and indications for CRT are unclear. There is evidence that the best treatment outcomes result from the administration of CRT to the group of children whose HF is caused by dyssynchrony mediated by traditional stimulation of the right ventricle in patient with complete atrioventricular block. On the contrary, the presence of dilated cardiomyopathy and functional Class III–IV HF are the predictors of ineffective CRT. Implantation of CRT devices in children has many peculiarities and challenges associated with anatomic and physiological characteristics of childhood age. Taking into consideration the expected length of treatment, one should admit that epicardial BiV stimulation should be preferred. In this paper, pathophysiology of the electromechanical dyssynchrony, experience with CRT, and suggestions for this kind of treatment has been discussed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, et al. Efficacy of ß blockers in patients with heart failure plus atrial fibrillation: An individual-patient data meta-analysis. Lancet 2014;384:2235-43.  Back to cited text no. 6
    
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Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014;370:1383-92.  Back to cited text no. 7
    
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Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, et al. Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 2014;370:1694-701.  Back to cited text no. 8
    
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Hindricks G, Taborsky M, Glikson M, Heinrich U, Schumacher B, Katz A, et al. Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): A randomised controlled trial. Lancet 2014;384:583-90.  Back to cited text no. 9
    
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Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients. 35th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT 2015) in Nice, France; April 17, 2015.  Back to cited text no. 10
    
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Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency . Eur Heart J 2015;36:657-68.  Back to cited text no. 11
    
12.
Cohen-Solal A, Damy T, Hanon O, Terbah M, Laperche T, Kerebel S, et al. High prevalence of iron deficiency in patients admitted for acute decompensated heart failure: A French study (CARDIOFER). J Am Coll Cardiol 2014;63:S12. [abstract]  Back to cited text no. 12
    
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Dunlay SM, Manemann SM, Chamberlain AM, Cheville AL, Jiang R, Weston SA, et al. Activities of daily living and outcomes in heart failure. Circ Heart Fail 2015;8:261-7.  Back to cited text no. 13
    
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Chahal H, Bluemke DA, Wu CO, McClelland R, Liu K, Shea SJ, et al. Heart failure risk prediction in the Multi-Ethnic Study of Atherosclerosis. Heart 2015;101:58-64.  Back to cited text no. 14
    
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Pasternak B, Svanström H, Melbye M, Hviid A. Association of treatment with carvedilol vs metoprolol succinate and mortality in patients with heart failure. JAMA Intern Med 2014;174:1597-604.  Back to cited text no. 15
    
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Kurt P, John N, John T, Peter E, Sue D. Effects of beta-blocker withdrawal in patients admitted with acute decompensated heart failure: A systematic review and meta-analysis. J Am Coll Cardiol 2015;65:s0735-1097.  Back to cited text no. 16
    
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Bayar N, Küçükseymen S, Göktas S, Arslan S. Right ventricle failure associated with trastuzumab. Ther Adv Drug Saf 2015;6:98-102.  Back to cited text no. 17
    
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Kayvanpour E, Mansi T, Sedaghat-Hamedani F, Amr A, Neumann D, Georgescu B, et al. Towards personalized cardiology: Multi-scale modeling of the failing heart. PLoS One 2015;10:e0134869.  Back to cited text no. 18
    
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