scholarly journals Raised homocystein plasma concentration in patients with Heart Failure: clinical significance

2016 ◽  
Vol 68 (2) ◽  
Author(s):  
E. Vizzardi ◽  
S. Nodari ◽  
C. Fiorina ◽  
M. Metra ◽  
L. Dei Cas

Elevated plasma levels of homocysteine is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies have demonstrated that hyperhomocysteinemia is an indipendent risk factor for vascular disease and is associated to heart failure. However there are no data regarding the association between homocysteine and various objective as well as subjective measures of heart failure. We hypothesized that plasma homocysteine is associated with clinical and echocardiographic signs of heart failure. On this ground we have analysed levels of homocysteine in patients with heart failure and possible correlation between these levels and clinical-functional pattern (NYHA class and ejection fraction). Methods: Plasma homocysteine levels were determined in 123 patients with dilated cardiomyopathy (59 males, 64 females, mean age 67±10 years, mean EF 31±11% and mean NYHA 2.4±0.9, 47 idiopatic and 76 postischemic cardiomyopathy) and 85 healthy control subjects (homogeneus group for sex and age). Patients with chronic renal failure, vitamin B12 and folate deficiency or factors affecting homocysteine plasma levels were escluded from this study. Homocysteine levels were determined in coded plasma samples by immunoenzimatic methods. Results: Patients with heart failure had a higher homocysteine level (mcg/L) than control subjects (21.72±10.28 vs 12.9±6.86, p<0,001) both postischemic (20.89±9.6 vs 12.9±6.86, p<0,001) and idiopatic cardiomiopathy (23.0±11.2 vs 12.9±6.86, p<0,001). A significant correlation was observed between homocysteine and NYHA functional class (p<0,001), age (p<0,001), creatinine (p<0,001), colesterol (p<0,05) while no correlations were observed with hemodynamic (HR, BP), functional (ejection fraction) and other metabolic parameters (triglycerides). Serum homocysteine was lowest in control and increased with increasing NYHA class. In idiopatic cardiomiopathy the correlation between homocysteine and NYHA functional class, creatinine (p<0,001), fibrinogen (p<0,05) was confirmed; in postischemic cardiomiopathy a significant correlation with creatinine and NYHA class (p<0,001) and with triglycerides (p<0,05) was also found. Conclusion: Plasma homocysteine was directly related to NYHA class. This observation may underline the strong relations of plasma homocysteine to congestive heart failure. Further research is indicated to evaluate a causal or noncausal mechanism for this association.

Author(s):  
Milton Packer ◽  
Stefan D. Anker ◽  
Javed Butler ◽  
Gerasimos S. Filippatos ◽  
João Pedro Ferreira ◽  
...  

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001. Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Yamauchi ◽  
I Morishima ◽  
Y Morita ◽  
K Takagi ◽  
H Nagai ◽  
...  

Abstract Background Although catheter ablation of atrial fibrillation (AF) has recently been shown to improve the cardiac function and even mortality in patients with heart failure (HF) and reduced ejection fraction (HFrEF), few studies have examined the outcomes of AF catheter ablation in patients with HF with preserved ejection fraction (HFpEF). Purpose To verify the impact of AF catheter ablation on the cardiac function and HF status in patients with HFpEF. Methods We studied 306 patients with HF who had a history of an HF hospitalization and/or preprocedural serum BNP levels &gt;100pg/ml (age, 68.9±8.2 years old; male, 66.3%; non-paroxysmal AF, 63.1%, left atrial diameter [LAD], 42.5±6.3 mm; left ventricular ejection fraction [LVEF], 60.6±12.0%) out of 596 consecutive patients who underwent pulmonary vein isolation-based catheter ablation of AF. The patients with an LVEF ≥50% were defined as having HFpEF (n=262; age, 69.0±8.2 years old; male, 64.5%; non-paroxysmal AF, 61.8%, LAD, 42.1±5.9 mm; left LVEF, 64.0±8.2%) and the remaining patients with an LVEF &lt;50% were defined as having HFrEF (n=44, age, 67.9±8.7 years old; male, 77.0%; non-paroxysmal AF, 70.5%, LAD, 44.9±8.2 mm; LVEF, 40.1±10.2%). The patients received periodic follow-ups for 12 months after the catheter ablation. The cardiac function parameters including the echocardiographic findings and HF functional status of the patients were compared between baseline and 12 months, stratified by the HF subgroup. Results AF recurred in 60 patients with HFpEF (22.9%) and in 14 with HFrEF (31.8%) during the 12 month follow-up (p=0.27), however, sinus rhythm was maintained at 12 months in most of the patients (253 patients with HFpEF [96.6%] and 42 patients with HFrEF [95.5%]) (p=0.71). Figure 1 compares the changes in the cardiac function parameters and NYHA functional class from baseline to the 12-month follow-up stratified by the HF subgroup. Both the patients with HFpEF and HFrEF had significant improvements in the serum BNP levels, chest thorax ratio, and LVEF determined by echocardiography. LA reverse remodeling as shown by a significant reduction in the LAD was observed in both HF subgroups, however, the E/E', an index of the LV diastolic function, did not significantly change in either of the subgroups. Similar to the patients with HFrEF, an improvement in the NYHA functional class was seen in those with HFpEF. Conclusions Catheter ablation of AF may benefit patients with HFpEF as well as those with HFrEF. Sinus rhythm maintenance achieved by AF catheter ablation in patients with HFpEF may lead to LA reverse remodeling and a better LV systolic function, thereby improving the NYHA functional class. It is unclear whether changes in the LV diastolic function may contribute to this favorable process. Funding Acknowledgement Type of funding source: None


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Seongkum Heo ◽  
Debra K Moser ◽  
Terry A Lennie ◽  
Mary Fischer ◽  
Eugene Smith ◽  
...  

Background: Patients with heart failure (HF) have notably poor health-related quality of life (HRQOL), which is associated with high hospitalization rates. Physical symptoms have been associated with poor HRQOL. However, whether improvement in physical symptoms actually leads to improvement in HRQOL has not fully examined in patients with HF. Purpose: To examine the effects of changes in physical symptoms on changes in HRQOL at 12 months, after controlling for age, comorbidities, New York Heart Association (NYHA) functional class, and modifiable psychosocial and behavioral factors. Methods: Data on physical symptoms (Symptom Status Questionnaire-HF) and HRQOL (Minnesota Living with Heart Failure) were collected from 94 patients with HF (mean age 58 ± 14 years, 44% male, 58% NYHA functional class II/III) at baseline and 12 month follow-up. Age, comorbidities, and NYHA functional class were collected using standard questionnaires at baseline. Psychosocial variables (depressive symptoms [Patient Health Questionnaire], perceived control [Control Attitudes Scale-Revised], and social support [Multidimensional Scale of Perceived Social Support]) and behavioral variables (medication adherence [Micro-Electro-Mechanical Systems], sodium intake [24-hour urine], and self-care management [Self-care management subscale of the Self-Care of Heart Failure Index]) were collected at baseline. Hierarchical multiple regression analyses were used to analyze the data. Results: The mean score changes in physical symptoms and HRQOL were -3.8 (± 14.1) and -9.2 (± 24.1), respectively (negative scores indicate improvement.). Among the sociodemographic and clinical characteristics, psychosocial variables, behavioral variables, baseline physical symptoms, and changes in physical symptoms, only changes in physical symptoms predicted changes in HRQOL at 12 months (F = 6.384, R2 = .46, p < .001). Improvement in physical symptoms led to improvement in HRQOL. Conclusion: It is critical to improve physical symptoms to improve HRQOL. Thus, development and delivery of effective interventions targeting improvement in physical symptoms are warranted in this population.


2021 ◽  
Vol 20 (7) ◽  
pp. 3068
Author(s):  
O. A. Osipova ◽  
E. V. Gosteva ◽  
T. P. Golivets ◽  
O. N. Belousova ◽  
O. A. Zemlyansky ◽  
...  

Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol  — MMP-1 decreased by 35% (p<0,01), MMP-9  — by 56,3% (p<0,001), TIMP-1  — by 17,9% (p<0,01); nebivolol  — MMP-1 decreased by 45% (p<0,001), MMP-9  — by 57,1% (p<0,001), TIMP-1  — by 30,1% (p<0,01); combination of bisoprolol with eplerenone  — MMP-1 decreased by 43% (p<0,001), MMP-9  — by 51,2% (p<0,001), TIMP-1  — by 25,1% (p<0,01); combination of nebivolol with eplerenone  — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9  — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.


2018 ◽  
Author(s):  
Jonathan-F. Baril ◽  
Simon Bromberg ◽  
Yasbanoo Moayedi ◽  
Babak Taati ◽  
Cedric Manlhiot ◽  
...  

BACKGROUND The New York Heart Association (NYHA) functional classification system has poor inter-rater reproducibility. A previously published pilot study showed a statistically significant difference between the daily step counts of heart failure (with reduced ejection fraction) patients classified as NYHA functional class II and III as measured by wrist-worn activity monitors. However, the study’s small sample size severely limits scientific confidence in the generalizability of this finding to a larger heart failure (HF) population. OBJECTIVE This study aimed to validate the pilot study on a larger sample of patients with HF with reduced ejection fraction (HFrEF) and attempt to characterize the step count distribution to gain insight into a more objective method of assessing NYHA functional class. METHODS We repeated the analysis performed during the pilot study on an independently recorded dataset comprising a total of 50 patients with HFrEF (35 NYHA II and 15 NYHA III) patients. Participants were monitored for step count with a Fitbit Flex for a period of 2 weeks in a free-living environment. RESULTS Comparing group medians, patients exhibiting NYHA class III symptoms had significantly lower recorded 2-week mean daily total step count (3541 vs 5729 [steps], P=.04), lower 2-week maximum daily total step count (10,792 vs 5904 [steps], P=.03), lower 2-week recorded mean daily mean step count (4.0 vs 2.5 [steps/minute], P=.04,), and lower 2-week mean and 2-week maximum daily per minute step count maximums (88.1 vs 96.1 and 111.0 vs 123.0 [steps/minute]; P=.02 and .004, respectively). CONCLUSIONS Patients with NYHA II and III symptoms differed significantly by various aggregate measures of free-living step count including the (1) mean and (2) maximum daily total step count as well as by the (3) mean of daily mean step count and by the (4) mean and (5) maximum of the daily per minute step count maximum. These findings affirm that the degree of exercise intolerance of NYHA II and III patients as a group is quantifiable in a replicable manner. This is a novel and promising finding that suggests the existence of a possible, completely objective measure of assessing HF functional class, something which would be a great boon in the continuing quest to improve patient outcomes for this burdensome and costly disease.


2020 ◽  
Vol 13 (Suppl_1) ◽  
Author(s):  
Andy T Tran ◽  
Paul S Chan ◽  
Phillip G Jones ◽  
John Spertus

Background: A foundation of current clinical trials is to categorize the severity of heart failure (HF) by New York Heart Association (NYHA) classification to ensure that enrolled patients have similar disease severity. Because the NYHA represents a clinician’s assessment of patients’ health status, it may vary from patients’ perspectives and can lead to more or less symptomatic patients being enrolled in clinical trials. We sought to directly compare the ranges of patient-reported health status, as assessed by the well-validated and reliable Kansas City Cardiomyopathy Questionnaire (KCCQ), with NYHA class in recent clinical studies. Methods: We used data from 2 contemporary HF clinical trials, HF-ACTION in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and TOPCAT in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), and 1 prospective cohort study, the KCCQ Interpretability study (KCCQINT) in patients with HFrEF, where both NYHA and the KCCQ were contemporaneously collected. The distributions of KCCQ Overall Summary (KCCQ-os) scores by NYHA and the variation in assigned NYHA classes among patients with KCCQ scores ≥80 (congruent with NYHA Class I) were then described. Results: A total of 6,072 patients (mean age 64±12 years, 41% female) were included across the 3 studies. Figure 1 shows marked overlap in KCCQ scores across NYHA classes. In KCCQINT, 148 (27%) out of 545 patients reported a KCCQ-os score ≥80, of whom 39 (26%), 81 (55%) and 28 (19%) were coded as NYHA Class I, II and III. None were classified as NYHA Class IV. In HF-ACTION, 677 (32%) of 2129 patients reported a KCCQ-os score ≥80, of whom 548 (81%), 128 (19%) and 1 (<1%) were coded as NYHA Class II, III and IV, respectively. In TOPCAT, 484 (14%) out of 3398 patients reported a KCCQ-os score ≥80, of whom 410 (85%) and 74 (15%) were considered NYHA Class I-II and III-IV, respectively. Conclusions: Although the NYHA is used to identify similarly ill patients for enrollment in clinical trials, there is marked variability within and across studies in patients’ self-reported health status. Future trials should consider patient-reported outcome measures as the basis for defining patient eligibility to enroll a more homogenous cohort of disease severity.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zamora ◽  
B Gonzalez ◽  
C Rivas ◽  
V Diaz ◽  
P Velayos ◽  
...  

Abstract Background Nutritional status is an important prognostic factor in patients with heart failure (HF) beyond body mass index, although its prognostic value in patients with mid-range left ventricular ejection fraction (HFmrEF) is not completely elucidated. In a pilot study we observed that the Mini Nutritional Assessment Short Form (MNA-SF) was the best approach for the screening of nutritional status in HF outpatients over others screening tools. Purpose To assess the prognostic role of malnutrition or risk of malnutrition in HFmrEF outpatients after the implementation of the MNA-SF screening tool in a routine way in a multidisciplinary HF. Methods The MNA-SF screening tool was administered during the global nurse evaluation of patients. The scoring ranges from 0 to 14, being 0 to7 as malnutrition status, 8 to 11 as at risk of malnutrition and 12 to 14 as normal nutritional status. For the present study those patients with malnutrition and at risk of malnutrition were merged and considered abnormal nutritional status. All-cause death was the primary end-point. Univariate and multivariate (backward conditional stepwise) Cox regression analyses were performed. Results Since October 2016 to November 2017, 153 HFmrEF patients were studied (mean age 68.8±11.7 years, 72.5% men, body mass index 28.4±4.4, LVEF 44% ± 3, NYHA class I 5.9%, II 86.3%, and III 7.8%). According to the MNA-SF 25 patients were (16.3%) fulfilled criteria of malnutrition (4) or where at risk of malnutrition (21). During a mean follow-up of 17.4±6.1 months, 23 patients died (15%). In the univariate analysis, nutritional abnormal status was significantly associated with all-cause death (HR 2.93 [1.23–7], p=0.02). In the multivariate analysis which included age, sex, NYHA functional class, body mass index, ischemic aetiology of HF and years of duration of HF, abnormal nutritional status remained significantly associated with all-cause mortality (HR 3.64 [1.39–9.54], p=0.009), together with NYHA functional class (HR 7.93 [2.69–23.4], p<0.001) and years of HF duration (HR 1.10 [1.04–1.16], p=0.001). Conclusions Nutritional status assessed with the screening MNA-SF was an independent predictor of all-cause death in ambulatory patients with HFmrEF – beyond BMI – together with NYHA functional class and HF duration.


2021 ◽  
Vol 26 (12) ◽  
pp. 4800
Author(s):  
M. V. Zhuravleva ◽  
S. N. Tereshchenko ◽  
I. V. Zhirov ◽  
S. V. Villevalde ◽  
T. V. Marin ◽  
...  

Aim. To assess the effect of therapy with sodium glucose co-transporter type 2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction (CHrEF) on the state cardiovascular mortality target indicators.Material and methods. All adult Russian patients with NYHA class II-IV HFrEF (left ventricular ejection fraction ≤40%) were considered as the target population. The characteristics of patients in the study corresponded to those in the Russian Hospital HF Registry (RUS-HFR). The study suggests that the use of dapagliflozin in addition to standard therapy will be expanded by 10% of the patient population annually in 2022-24. Cardiovascular mortality modeling was performed based on the extrapolation of DAPA-HF study result. The number of deaths that can be prevented was calculated when using dapagliflozin in addition to standard therapy. Further, the contribution of prevented deaths with dapagliflozin therapy to the achievement of federal and regional cardiovascular mortality target indicators (1, 2 and 3 years) was calculated.Results. The use of dapagliflozin in addition to standard therapy for patients with NYHA class II-IV CHrEF with the expansion of dapagliflozin therapy by 10% of the patient population annually will additionally prevent 1729 cardiovascular death in the first year. This will ensure the implementation of cardiovascular mortality target indicators in Russia in 2022 by 11,8%. In the second year, 3769 cardiovascular deaths will be prevented, which will ensure the implementation of target indicators in 2023 by 17,2%. In the third year, 5465 cardiovascular deaths prevented, which will ensure the implementation of implementation of target indicators in 2024 by 18,7%.Conclusion. The use of dapagliflozin in addition to standard therapy for patients with NYHA class II-IV CHrEF will ensure the implementation of implementation of target indicators in 2024 by 18,7%.


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