Impact of cellular myocardial infiltration on clinical outcome in non-ischaemic heart failure

2021 ◽  
pp. jclinpath-2020-206964
Author(s):  
Edyta Reichman-Warmusz ◽  
Jolanta Nowak ◽  
Krzysztof Kaczmarek ◽  
Ewa Nowalany-Kozielska ◽  
Romuald Wojnicz
Keyword(s):  
Heart Failure ◽  
Clinical Outcome ◽  
Negative Correlation ◽  
Troponin T ◽  
High Power Field ◽  
Predisposing Factor ◽  
Inflammatory Infiltration ◽  
Definition Of ◽  
The Impact

AimsSo far, little has been known on whether myocardial inflammatory infiltration influences heart failure (HF) progression. Thus, the aim of this study was to test the impact of intramyocardial infiltration on clinical outcomes.MethodsBiopsy samples from 358 patients with stable HF secondary to dilated cardiomyopathy were studied. Immunohistochemistry for lymphocyte (CD3) and macrophage (CD68) markers was performed and counted. After a 1-year follow-up, patients were classified as improved based on the predefined definition of improvement. The clinical data were collected from 324 patients (90.5%).ResultsAccording to the predefined definition of improvement, 133 patients improved (41.0%) but 191 remained unchanged or deteriorated (58.9%). After a 12-month follow-up, the OR with 95% CI of counts of myocardial inflammatory CD68-positive ≥4 cell/high power field (HPF) compared with CD68-positive <4 cell/HPF for lack of improvement was 1.91 (1.65–2.54). However, the number of CD3 positive cell infiltration had no impact on clinical outcome after a 1-year follow-up. In the baseline study, a reasonably negative correlation was found between the number of CD68 positive cells and troponin T (r=−0.39; p<0.001 by Spearman’s r). This was corroborated with a low negative correlation between these cells and myocardial form of creatine kinase (CK-MB) fraction (r=−0.27; p=0.006). There was no correlation between CD3 and CD68 positive cells (Spearman’s r; r=−0.17, p=0.16).ConclusionsThe current results provide evidence that high macrophage counts may be a predisposing factor for HF progression.

scholarly journals Biomarkers-based personalized follow-up in chronic heart failure improves patient’s outcomes and reduces care associate cost

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Leon-Justel ◽  
Jose I. Morgado Garcia-Polavieja ◽  
Ana Isabel Alvarez-Rios ◽  
Francisco Jose Caro Fernandez ◽  
Pedro Agustin Pajaro Merino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hospital Admissions ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Ventricular Ejection Fraction ◽  
Number Of Patients ◽  
Ed Visits ◽  
The Impact

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

scholarly journals Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rameen Shakur ◽  
Juan Pablo Ochoa ◽  
Alan J. Robinson ◽  
Abhishek Niroula ◽  
Aneesh Chandran ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systems Biology ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Clinical Data ◽  
Cardiac Death ◽  
Troponin T ◽  
Management Options ◽  
Familial Cardiomyopathy ◽  
The Impact

AbstractThe cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90–129 and 130–179 when compared to amino acids 1–89 and 200–288. Our data support variations among 90–130 as being a hotspot for sudden cardiac death and the region 131–179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90–129 and 130–180) and low risk (regions 1–89 and 200–288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification.

scholarly journals Associations between left bundle branch block with different PR intervals, QRS durations, heart rates and the risk of heart failure: a register-based cohort study using ECG data from the primary care setting

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Marc Meller Søndergaard ◽  
Johannes Riis ◽  
Karoline Willum Bodker ◽  
Steen Møller Hansen ◽  
Jesper Nielsen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Care ◽  
Heart Rate ◽  
Left Bundle Branch Block ◽  
Bundle Branch Block ◽  
Increased Risk ◽  
Pr Interval ◽  
Qrs Duration ◽  
The Impact

AimLeft bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.Methods and resultsUsing ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment.ConclusionProlonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.

scholarly journals Serially measured cytokines and cytokine receptors in relation to clinical outcome in patients with stable heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Bouwens ◽  
A Schuurman ◽  
K.M Akkerhuis ◽  
S.J Baart ◽  
K Caliskan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcome ◽  
Primary Endpoint ◽  
Nyha Class ◽  
Cytokine Receptors ◽  
Funding Source ◽  
Compensatory Mechanism ◽  
Blood Samples ◽  
Two Samples

Abstract Background Activation of the inflammatory response in heart failure (HF) may initially serve as a compensatory mechanism. However, on the longer term, this physiological phenomenon can become disadvantageous. Temporal patterns of inflammatory proteins other than CRP have not yet been investigated in patients with stable HF. Purpose We aimed to evaluate the association of 17 serially measured cytokines and cytokine receptors with clinical outcome in patients with stable heart failure. Methods In 263 patients, 1984 serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The primary endpoint (PE) composed of cardiovascular mortality, HF-hospitalization, heart transplantation, and LVAD. We selected baseline blood samples in all patients, as well as the two samples closest to the primary endpoint, and the last sample available in event-free patients. Thus, in 567 samples we measured 17 cytokines and cytokine receptors using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and PE were investigated by joint modelling. Results Median age was 68 (IQR: 59–76) years, with 72% men, 74% NYHA class I-II and a median ejection fraction of 30% (23–38%). 70 patients reached a PE. After adjustment for clinical characteristics (age, sex, diabetes, atrial fibrillation, NYHA class at baseline, diuretics and systolic blood pressure), 7 biomarkers were associated with the PE (Figure). Interleukin-1 receptor type 1 (IL1RT1) showed the strongest association: HR 2.65 [95% CI: 1.78–4.21]) per standard deviation change in level (NPX) at any point in time during follow-up, followed by Tumor necrosis factor receptor 1 (TNF-R1): 2.25 [1.66–3.08], and C-X-C motif chemokine 16 (CXCL16): 2.18 [1.59–3.04]. After adjustment for baseline N-terminal pro–B-type natriuretic peptide, high-sensitive troponin T and C-reactive protein however, only IL1RT1 and TNF-R1 remained significantly associated with the PE. Conclusion Repeatedly measured levels of several cytokines and cytokine receptors are independently associated with clinical outcome in stable HF patients. These results suggest that repeated measurements of these biomarkers, in addition to established cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients. Figure 1. Associations between levels of cytokines and cytokine receptors and the primary endpoint. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

MOBILE APPLICATION REMOVES SOCIETAL BARRIERS TO P4 MEDICINE

2017 ◽  
pp. 1-3
Author(s):  
J.-P. Michel
Keyword(s):  
Cognitive Abilities ◽  
Mobile Application ◽  
New Technologies ◽  
Global Evaluation ◽  
P4 Medicine ◽  
Fertile Ground ◽  
Definition Of ◽  
The Individual ◽  
The Impact

The overlap between one innovative paradigm (P4 medicine: predictive, personalized, participatory and preventive) and another (a new definition of “Healthy ageing”) is fertile ground for new technologies; a new mobile application (app) that could broaden our scientific knowledge of the ageing process and help us to better analyse the impact of possible interventions in slowing the ageing decline. A novel mobile application is here presented as a game including questions and tests will allow in 10 minutes the assessment of the following domains: robustness, flexibility (lower muscle strength), balance, mental and memory complaints, semantic memory and visual retention. This game is completed by specific measurements, which could allow establishing precise information on functional and cognitive abilities. A global evaluation precedes advice and different types of exercises. The repetition of the tests and measures will allow a long follow up of the individual performances which could be shared (on specific request) with family members and general practitioners.

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Total Mortality ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

scholarly journals Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy

2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Tachyarrhythmias ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
The Impact

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

Abstract MP25: Obesity, Heart Failure Risk & Cardiorespiratory Fitness

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Peter F Kokkinos ◽  
Puneet Narayan ◽  
Charles Faselis ◽  
Jonathan Myers ◽  
Carl Lavie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Capacity ◽  
Cardiorespiratory Fitness ◽  
Reference Group ◽  
Normal Weight ◽  
Entire Cohort ◽  
Metabolic Equivalents ◽  
Increased Risk ◽  
The Impact

Introduction: Obesity, defined as body mass index (BMI) ≥30 kg/m 2 , is associated with increased incidence of heart failure (HF). Increased cardiorespiratory fitness (CRF), as indicated by increased exercise capacity, is associated with lower risk of cardiovascular disease and HF. However, the CRF-BMI-HF interaction has not been fully explored. Hypothesis: We assessed the hypothesis that the risk of HF associated with increased BMI is moderated by increased CRF. Methods: We identified 19,881 Veterans (mean age: 58.0±11.3 years) who completed an exercise tolerance test (ETT) to assess either CRF status or suspected ischemia at two VA Medical Centers (Washington DC and Palo Alto, CA). None had documented HF at baseline or evidence of ischemia during the ETT. We established four BMI categories: <25 kg/m 2 ; 25-29.9 kg/m 2 ; 30-34.9 kg/m 2 ; and ≥35 kg/m 2 . In addition, we established four CRF categories based on age-stratified quartiles of peak metabolic equivalents (METs) achieved (mean ± SD): Least-Fit (4.5±1.2 METs; n=4,743); Low-Fit (6.6±1.3; n=5,103); Moderate-Fit (8.0±1.3 METs; n=5,084); and High-Fit (11.1±2.4 METs; n=4,951). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of HF across BMI categories for the entire cohort, using BMI 25-29.9 kg/m 2 (lowest HF rate) as the reference group. We then stratified the cohort by the four BMI categories and assessed HF risk across CRF categories within each stratum, using the Least-fit category as the reference group. The models were adjusted for age, race, gender, cardiac risk factors, sleep apnea, alcohol dependence, medications. Results: During follow-up (median=11.8 years), 2,193 developed HF (10.5 per 1,000 person-years of follow-up). The HF risk for normal weight individuals (18.5-24.9 kg/m2) was 10% higher (p=0.93). For obese individuals, the HF risk was 22% higher in those with BMI 30-34.9 kg/m 2 (HR=1.22; 95% CI: 1.09-1.35) and 50% higher (HR=1.50, 95% CI: 1.32-1.72) for those with BMI ≥35 kg/m 2 . When CRF (peak METs achieved) was introduced in the model, the risk for those with BMI 30-34.9 was reduced from 22% to 16% (HR=1.16; 95% CI: 1.04-1.29) and from 50% to 29% (HR=1.29; 95% CI: 1.13-1.48) among those with ≥35 kg/m 2 . For every 1-MET increase in exercise capacity, HF risk was 15% lower (HR=0.85; 95% CI: 0.83-0.87). We then assessed the impact of CRF on the risk of HF within each of the four BMI categories. The HF risk declined progressively (range: 25% to 69%; p<0.01) with increasing fitness within all BMI categories. Conclusions: The obesity-associated increased risk of HF was attenuated by increased CRF. The HF risk was progressively decreased with increased CRF within all BMI categories.

Abstract 13487: Impact of the New Definition of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Fusako Sera ◽  
Tomohito Ohtani ◽  
kei nakamoto ◽  
Shungo Hikoso ◽  
Daisaku Nakatani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Pulmonary Artery ◽  
Rank Test ◽  
Heart Catheterization ◽  
Preserved Ejection Fraction ◽  
Multicenter Observational Study ◽  
Definition Of ◽  
The Impact

Introduction: The proposed revision of hemodynamic definition of pulmonary hypertension (PH) adopts a lower threshold of mean pulmonary artery pressure (mPAP) > 20 mmHg. In addition, pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is included as the definition of pre-capillary component of PH. Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pre-capillary PH as well as post-capillary PH. We aimed to investigate the impact of the proposed definition of PH on clinical diagnosis of PH associated with HFpEF. Methods: From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 225 patients who were hospitalized with HF and underwent right heart catheterization were categorized according to the current guidelines and the proposed definition of PH: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). In the proposed definition, patients with mPAP > 20 mmHg, PVR < 3 WU, and pulmonary artery wedge pressure ≤ 15 mmHg do not meet criteria for any of the above categories and are categorized as “unclassified PH”. Results: Prevalence of PH was significantly increased in the proposed definition compared to that in the current definition (51% vs 29%, p<0.0001), with a doubled frequency of pre-capillary PH (Fig A). Furthermore, 24 patients (11%) were diagnosed as unclassified PH and accounted for 22% of those with PH by the proposed definition. Among the PH categories in the proposed definition, Cpc-PH category was significantly relevant for worse prognosis at 1 year after discharge in patients with HFpEF (p=0.03 vs non-PH by log-rank test with Bonferroni's correction) (Fig 2). Conclusions: The new definition of PH resulted in a remarkable increase of prevalence of PH in HFpEF with a quite a few patients with unclassified PH and doubled frequency of pre-capillary PH.

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