Non-ischaemic Systolic Heart Failure Research Articles

P4703Impaired myocardial perfusion is associated with increasing left ventricular mass in patients with non-ischaemic systolic heart failure: a cross-sectional study using Rubidium-82 PET/CT

P4703Impaired myocardial perfusion is associated with increasing left ventricular mass in patients with non-ischaemic systolic heart failure: a cross-sectional study using Rubidium-82 PET/CT

Myocardial perfusion during atrial fibrillation in patients with non-ischaemic systolic heart failure: a cross-sectional study using Rubidium-82 positron emission tomography/computed tomography.

Patients with non-ischaemic systolic heart failure often have reduced myocardial blood flow without significant coronary atherosclerosis. Likewise, patients with atrial fibrillation (AF) have reduced myocardial perfusion during AF compared with sinus rhythm. The aim of this study was to explore whether there is an additive negative effect of AF during scan on the myocardial perfusion in patients with non-ischaemic systolic heart failure. We included 27 young healthy controls and 114 patients with non-ischaemic systolic heart failure to a Rubidium-82 positron emission tomography/computed tomography perfusion scan (23 with AF during scan). To obtain the myocardial flow reserve (MFR = stress flow/rest flow), patients were scanned at rest and during adenosine-induced stress. Among patients, those with AF were older [years: 73; interquartile range (IQR) 65-78 vs. 67; IQR 60-74; P = 0.03] and more were men (87% vs. 62%; P = 0.02). Distribution of sex in controls did not differ from either patient group. Patients with AF had significantly lower MFR than patients without [MFR: 1.87; 95% confidence interval (CI) 1.58-2.22 vs. 2.50; 95% CI 2.06-2.86; percent difference: -21.5%; P = 0.01]. MFR remained significantly lower in the group with AF (estimate -24.2%; 95% CI -39.6% to -4.8%; P = 0.02) in an adjusted multivariable regression analysis. Further, patients had lower MFR compared with controls: 3.46; 95% CI 3.03-3.94; P < 0.0001. Additionally, coronary vascular resistance was highest in patients with AF and lowest in controls. Patients with systolic heart failure had lower flow reserve than healthy controls and even lower MFR if they had AF during scan.

Should Primary Prevention ICDs Still Be Placed in Patients with Non-ischemic Cardiomyopathy? A Review of the Evidence

Recent evidence has suggested that implantable defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit in the presence of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT). Despite significant benefits of GDMT and CRT, current evidence is derived from ICD trials that rely predominantly on reduced left ventricular ejection fraction alone (LVEF). The majority of patients with sudden cardiac death (SCD) have LVEF > 30% indicating that LVEF by itself is an inadequate predictor of SCD. The Danish study to assess the efficacy of ICD in patients with non-ischemic systolic heart failure on mortality (DANISH) highlights the importance of better risk stratifying NICM patients for ICD implantation. Assessment of life expectancy, comorbidities, presence of advanced heart failure, etiology of NICM, and the presence of myocardial fibrosis can help risk stratify ICD beyond LVEF. Genetics and biomarkers can be of further assistance in risk stratification.

Contractile reserve as a predictor of prognosis in patients with non-ischaemic systolic heart failure and dilated cardiomyopathy: a systematic review and meta-analysis

Objective: Patients with non-ischaemic systolic heart failure (HF) and idiopathic dilated cardiomyopathy (DCM) are a heterogenous group with varied morbidity and mortality. Prognostication in this group is challenging. We performed a systematic review and meta-analysis to examine the significance of the presence of contractile reserve as assessed via stress imaging on mortality and hospitalisation.Methods: A search for studies that non-invasively assessed contractile reserve in patients with DCM or non-ischaemic HF with reduced ejection fraction, stress imaging with follow-up data comparing outcomes. A range of imaging modalities and stressors were included. We examined primary endpoints of mortality and secondary endpoints of combined cardiovascular events including HF progression or hospitalisation. Our analysis compared endpoints in patients with contractile reserve and those without it.Results: Nine prospective cohort studies were identified describing a total of 787 patients. These studies are methodologically but not statistically heterogenous (I2 = 31%). Using a random effect model, the presence of contractile reserve was associated with a significantly lower risk of mortality and cardiovascular events odds ratios of 0.20 (CI 0.11, 0.39) (P < 0.00001) and 0.13 (CI 0.04, 0.40) (P = 0.0004), respectively.Conclusion: Regardless of stressor and imaging modality and despite the significant methodological heterogeneity within the current data (imaging techniques and parameters), patients with non-ischaemic cardiomyopathy and reduced EF who demonstrate contractile reserve have a lower mortality, and lower events/hospitalisations. The presence of contractile reserve therefore offers a potential positive prognostic indicator when managing these patients.

Myocardial perfusion in patients with non-ischaemic systolic heart failure and type 2 diabetes: a cross-sectional study using Rubidium-82 PET/CT.

Both patients with non-ischaemic systolic heart failure and patients with type 2 diabetes (T2DM) often have reduced myocardial blood flow without significant coronary atherosclerosis. However, the mechanisms are not fully understood. The aim of this study was to investigate whether perfusion is reduced additionally when the 2 are combined. In a cross-sectional study, we scanned patients with non-ischaemic systolic heart failure with and without T2DM using Rubidium-82 positron emission tomography/computed tomography at rest and adenosine-induced stress, thereby obtaining the myocardial flow reserve (myocardial flow reserve (MFR) = stress flow/rest flow) as a measure of the myocardial vasomotor function; 28 patients with T2DM and 123 without T2DM were included. All patients received heart failure treatment according to guidelines. Multiple regression analysis was performed to assess the association between T2DM and MFR. Age [68 (60-75) years vs. 68 (62-72) years; P = 0.84] and female sex (21% vs. 33%; P = 0.26) were similar between patients with and without T2DM. Patients with T2DM had higher body mass index, (29.9 vs. 26.5kg/m2; P = 0.02), higher blood glucose (6.2 vs. 5.7mmol/L; P = 0.03), more often hypertension (50 vs. 27%; P = 0.02) and received more cholesterol lowering medication (61 vs. 35%; P = 0.02). Apart from this, the groups were similar. In a multivariable analysis, MFR was 16% lower in patients with T2DM compared with patients without [estimate - 16%; 95% confidence interval (CI) - 29 to - 0.7%; P = 0.04]. Patients with T2DM and systolic heart failure have lower myocardial flow reserve compared with heart failure patients without T2DM.

4778Impaired myocardial perfusion during atrial fibrillation in patients with non-ischaemic systolic heart failure - A cross-sectional study using Rubidium-82 PET/CT

4778Impaired myocardial perfusion during atrial fibrillation in patients with non-ischaemic systolic heart failure - A cross-sectional study using Rubidium-82 PET/CT

295Myocardial fibrosis and the effect of defibrillator implantation in patients with non-ischemic systolic heart failure - DANISH-MRI

295Myocardial fibrosis and the effect of defibrillator implantation in patients with non-ischemic systolic heart failure - DANISH-MRI

British Society for Heart Failure: 7th nurse training day

British Journal of Cardiac NursingVol. 12, No. 5 Meeting ReportBritish Society for Heart Failure: 7th nurse training dayWendy Bannister, Jenny Hibberd, Jayne Masters, Clare WeaverWendy BannisterSearch for more papers by this author, Jenny HibberdSearch for more papers by this author, Jayne MastersSearch for more papers by this author, Clare WeaverSearch for more papers by this authorWendy Bannister; Jenny Hibberd; Jayne Masters; Clare WeaverPublished Online:5 May 2017https://doi.org/10.12968/bjca.2017.12.5.255AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Christakis NA, Lamont EB (2000) Extent and determinants of error in doctors' prognoses in terminally ill patients: prospective cohort study. BMJ 320(7233): 469–72 Crossref, Google ScholarKøber L, Thune JJ, Nielsen JC et al.; DANISH Investigators (2016) Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. New Engl J Med 375(13): 1221–30. doi: https://doi.org/10.1056/NEJMoa1608029 Crossref, Google ScholarNational Comprehensive Cancer Network (2003) Distress management. Clinical practice guidelines. J Natl Compr Canc Netw 1(3): 344–74 Crossref, Google ScholarPonikowski P, Voors AA, Anker SD et al. (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27): 2129–200. doi: https://doi.org/10.1093/eurheartj/ehw128 Crossref, Google ScholarRollnick S, Miller W (2008) Motivational Interviewing in Health Care. 3rd edn. Guildford Press, New York Google ScholarSteinhauser KE, Christakis NA, Clipp EC, McNeilly M, McIntyre L, Tulsky JA (2000) Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA 284(19): 2476–82 Crossref, Google Scholar FiguresReferencesRelatedDetails 2 May 2017Volume 12Issue 5ISSN (online): 2052-2207 Metrics History Published online 5 May 2017 Published in print 2 May 2017 Information© MA Healthcare LimitedAcknowledgementsThe day concluded with the programme directors thanking both delegates and faculty for their contributions to the day. The Society would also like to gratefully acknowledge the support provided by the Friends of the BSH (Abbott, Bayer, Medtronic, Novartis Pharmaceuticals, Roche Diagnostics, Servier Laboratories, Vifor Pharma).PDF download

Implantable Cardioverter-defibrillator for Primary Prevention of Sudden Cardiac Death in Non-ischemic Cardiomyopathy

The insertion of implantable cardioverter-defibrillators (ICD) in patients with non-ischemic cardiomyopathy (NICM) has been recommended by recent guidelines. However, current evidence shows limited benefits to inserting ICDs in patients with NICM. Recently, the defibrillator implantation in patients with non-ischemic systolic heart failure (DANISH) trial, a large randomized trial of more than 1,100 patients with NICM, was conducted to compare the primary prevention of all-cause mortality between optimal medical therapy, cardiac resynchronization therapy, and ICD implantation. The DANISH trial revealed no differences in all-cause mortality between the groups after 5 years. However, in patients younger than 68 years of age, the rate of death from any cause was significantly lower in the ICD group compared to the control group. In addition, the rate of sudden cardiac death was lower in the ICD group compared to the control group in patients under 68 years. The results of DANISH will likely change guidelines about the insertion of ICD in patients with NICM, and encourage the use of ICD in patients with NICM. Keywords: Implantable cardioverter-defibrillator; Non-ischemic cardiomyopathy; Sudden cardiac death; Primary prevention 중심 단어: ì‚½ìž í˜• ì œì„¸ë™ê¸°; 비허혈성 심근병증; 심장돌연사; ì¼ì°¨ì  예방

In nonischemic systolic heart failure, prophylactic ICDs did not reduce all-cause mortality compared with usual care.

Source Citation Kober L, Thune JJ, Nielsen JC, et al; DANISH Investigators. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375:1221-30. 27571011

Rationale, design, and baseline characteristics of the DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillators in patients with non-ischemic Systolic Heart failure on mortality (DANISH)

The effect of an implantable cardioverter defibrillator (ICD) in patients with symptomatic systolic heart failure (HF) caused by coronary artery disease is well documented. However, the effect of primary prophylactic ICDs in patients with systolic HF not due to coronary artery disease is much weaker. In addition, HF management has improved, since the landmark ICD trials and a large proportion of patients now receive cardiac resynchronization therapy (CRT) where the effect of ICD treatment is unknown. In the DANISH study, 1,116 patients with symptomatic systolic HF not caused by coronary artery disease have been randomized to receive an ICD or not, in addition to contemporary standard therapy. The primary outcome of the trial is time to all-cause death. Follow-up will continue until June 2016 with a median follow-up period of 5 years. Baseline characteristics show that enrolled patients are treated according to current guidelines. At baseline, 97% of patients received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% received a β-blocker, 58% a mineralocorticoid receptor antagonist, and 58% were scheduled to receive CRT. Median age was 63 years (range, 21-84 years) at baseline, and 28% were women. DANISH will provide pertinent information about the effect on all-cause mortality of a primary prophylactic ICD in patients with symptomatic systolic HF not caused by coronary artery disease on contemporary standard therapy including CRT.

Multivariate miRNA signatures as biomarkers for non-ischaemic systolic heart failure

Non-ischaemic heart failure is one of the today's most prevalent cardiovascular disorders. Since modern pharmacotherapy has proved to be very effective in delaying disease progression and preventing death, imaging modalities and molecular biomarkers play an important role in early identification and clinical management as well as risk assessment of patients. The present study evaluated for the first time whole peripheral blood miRNAs as novel biomarker candidates for non-ischaemic heart failure with reduced ejection fraction (HF-REF). We assessed genome-wide miRNA expression profiles in 53 HF-REF patients and 39 controls. We could identify and validate several miRNAs that show altered expression levels in non-ischaemic HF-REF, discriminating cases from controls both as single markers or when combined in a multivariate signature. In addition, we demonstrate that the miRNAs of this signature significantly correlate with disease severity as indicated by left ventricular ejection fraction. Our data further denote that miRNAs are potential biomarkers for systolic heart failure. Since their detection levels in whole blood are also related to the degree of left ventricular dysfunction, they may serve as objective molecular tools to assess disease severity and prognosis.

Skeletal muscle ATP kinetics during exercise in patients with systolic heart failure

Background Creatine kinase (CK) reaction is the primary energy reserve reaction in skeletal muscle (SM), providing additional ATP during exercise. Although exercise intolerance is a major limitation in systolic heart failure (SHF), the rate of ATP delivery by CK (CK flux) has not been studied during exercise in healthy subjects (HS) or SHF patients. We hypothesized that SM high-energy phosphates and CK flux are reduced at rest and during low intensity plantar flexion exercise (PFE) in mild-moderate SHF patients. Methods 14 non-ischemic SHF patients (EF<40) and 11 HS underwent 31P magnetic resonance spectroscopy with saturation transfer (MRST) measures of gastrocnemius creatine phosphate-to-ATP (PCr/ATP) and CK pseudo-first-order rate constant, k, at rest and during PFE in a Philips 3T MRI/ MRS system. Single-leg PFE involved lifting 0.9 kg/sec on a custom built non-magnetic device for 8.5 minutes. [ATP] (umol/g) was taken as 5.2umol/g for both groups and [PCr](umol/g) was calculated as (PCr/ATP)*(5.2umol/g) and CK flux (umol/g/s) as ([PCr]*k). Comparisons were made with paired and non-paired t-testing using XLSTAT package.

Statins Do Not Significantly Affect Muscle Sympathetic Nerve Activity in Humans With Nonischemic Heart Failure: A Double-Blind Placebo-Controlled Trial

Background Hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) have been shown to reduce sympathetic nervous system (SNS) activation in experimental heart failure (HF). However, this potential mechanism of action of statins in HF has not been well studied in humans. Methods and Results Twenty-six patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] ≤35%) were randomized to atorvastatin (10 mg) or placebo for 3 months. Pre- and posttreatment testing included echocardiography, laboratory assays, quality of life (QOL) questionnaires, and peroneal nerve muscle sympathetic nerve activity (MSNA) via microneurography. Eighteen subjects had technically adequate MSNA tracings before and after treatment. The cohort was 65% male, 81% New York Heart Association functional class II, LVEF 26 ± 6%, and low-density lipoprotein cholesterol (LDL-C) 108 ± 26 mg/dL. Baseline MSNA was 41 ± 2 bursts/min. LDL-C significantly decreased in the atorvastatin (−36.8%) versus the placebo (−0.1%) group ( P < .0001). However, there was no significant change in MSNA (−16.2% vs −2.5%), LVEF, B-type natriuretic peptide, or QOL score in the atorvastatin compared with the placebo group. Conclusions Short-term statin therapy in patients with nonischemic HF does not result in a significant decrease in SNS activation as measured by MSNA. These findings are consistent with the neutral outcomes of large clinical trials of statins in HF.

Total cholesterol levels and mortality risk in nonischemic systolic heart failure

Prior studies have demonstrated that low serum total cholesterol (TC) is associated with increased mortality in heart failure (HF); however, this association has not been consistently observed in HF of nonischemic etiology. We analyzed a cohort of 614 patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] <40%). Fasting lipid panels were drawn at time of referral. Patients were stratified into quartiles of TC (Q1 <133, Q2 134-168, Q3 169-209, and Q4 >210 mg/dL). The cohort was 68% male, mean age was 48 +/- 13 years, and LVEF was 23% +/- 7%. Patients with lower serum TC had worse hemodynamic profiles, lower LVEF, and higher New York Heart Association class. Low TC was associated with increased risk of 1-year death and urgent transplant (UT) (49%, 29%, 18%, 14% for Q1-Q4 respectively, P < .0001) as well as all-cause mortality (P < .0001). On multivariate analysis, adjusting for multiple HF prognostic factors, low TC proved to be an independent predictor of worse outcomes, with hazard ratios for death and UT of 3.4, 1.8, and 1.6 for Q1 to Q3, respectively, compared with Q4. Based on receiver operating characteristic curve analysis, the best cutoff for prediction of death and UT for TC was 161 mg/dL. Low TC is strongly associated with increased mortality in patients with nonischemic, systolic HF. Further research is necessary to determine the nature of this relationship, optimal lipid levels, and the therapeutic role, if any, of statins in patients with established HF.

Dobutamine-induced augmentation of left ventricular ejection fraction predicts survival of heart failure patients with severe non-ischaemic cardiomyopathy.

The prognosis of patients with severe non-ischaemic dilated cardiomyopathy is variable. The predictive value of currently utilized tests is suboptimal. The purpose of this study was to determine the prognostic value of dobutamine-induced augmentation of left ventricular ejection fraction in patients with non-ischaemic dilated cardiomyopathy. Sixty-two patients with left ventricular ejection fraction < or =0.30 underwent exercise testing with gas exchange analysis and assessment of left ventricular ejection fraction at rest and after a 10-min intravenous infusion of dobutamine at 10 microg x kg(-1) x min(-1), using equilibrium radionuclide ventriculography. Age was 48+/-11 years, 32% females, functional class 2.6+/-0.6, resting left ventricular ejection fraction 0.20+/-0.06, and peak exercise oxygen consumption (mVO2) 19+/-6 ml x kg(-1) x min(-1). Mean dobutamine-induced augmentation of left ventricular ejection fraction (DeltaLVEF) was 0.09+/-0.06 (median 0.08, range -0.03 to 0.26). Follow-up was 25+/-15 months during which there were 12 deaths and five transplantations. Patients were divided into two groups based on median DeltaLVEF. The transplant-free survival was better in the group with higher DeltaLVEF (94% vs 64%, P<0.008). In multivariate analysis incorporating age, gender, duration of chronic heart failure, functional class, right and left ventricular ejection fraction, DeltaLVEF, left ventricular end-diastolic volume index, and mVO2, only DeltaLVEF was predictive of 1-year, 3-year, and overall transplant-free survival (RR 0.09, 0.03, and 0.13;P 0.03, 0.09, and 0.08 respectively). The linear correlation between DeltaLVEF and mVO2(r=0.3) and between DeltaLVEF and left ventricular ejection fraction (r=0.5) was weak. Dobutamine-induced augmentation of left ventricular ejection fraction is a strong prognostic variable, independent of exercise capacity and resting ventriculographic variables, in severe non-ischaemic systolic dysfunctional heart failure.