P1619Polymorphic variants rs6684209 and rs7521023 of the calsequestrin 2 gene as risk factors for adverse course of heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Muslimova ◽  
T Rebrova ◽  
S Akhmedov ◽  
S Afanasyev

Abstract Calsequestrin 2 protein binds most of Ca2+ ions inside the sarcoplasmic reticulum and is involved in the regulation of Ca2+ release through the ryanodine receptors of the cardiomyocytes. Due to mutations in the CASQ2 gene, there is an enhanced release of ions from the sarcoplasmic reticulum, which leads to disruption of Ca2+ homeostasis. In turn, this is a risk factor for the development and progression of chronic heart failure (CHF) and heart rhythm disturbances. Purpose Investigate the association between polymorphic variants rs6684209, rs7521023 of the CASQ2 gene and heart failure in patients with coronary artery disease (CAD). Methods The sample included 174 patients with CAD complicated by CHF. Of these, 115 (66.1%) are men and 59 (33.9%) are women aged 64 (59; 70) years. The functional class (FC) of CHF was defined according to the classification of the New York Heart Association (NYHA). The distribution of CHF FC I, FC II, FC III was 25 (14.4%), 97 (55.7%), 52 (29.9%). The left ventricular ejection fraction in the patient sample was 62% (52; 66). The polymorphic variants rs6684209 (115707991C>T in the intron) and rs7521023 (115700759G>A in 3-UTR) of the CASQ2 gene were determined by real-time polymerase chain reaction. For the analysis of the qualitative data, Pearson's χ2 test or the Fisher two-sided exact test was used. Results In the total sample of patients, there was no assotiation between the rs6684209 variant of the CASQ2 gene and the clinical picture of CHF. However, among men, but not women, differences in the frequency of FC I, II, III CHF (p=0.029) between CC, CT and TT genotypes were found. In addition, among carriers of the CT genotype, diastolic myocardial dysfunction occurred in 80% of patients, while among CC homozygotes, its frequency was 63.1% and was not observed in TT homozygotes (p=0.034). At the same time, there were more patients with heart rhythm disorders among CC homozygotes than among carriers of the T allele (60.8% vs. 45.2% for CT and 0% for TT, p=0.046). The association of the polymorphic variant rs7521023 with the course of CHF was assessed. A significant (p=0.044) increase in the frequency of left atrial enlargement in GG homozygotes (69.2%) compared with carriers of the AA (45.1%) and AG (41.9%) genotypes was found in the total sample of patients. Gender features were absent in the association of variant rs7521023 with risk factors for the development and progression of CHF. Conclusion The polymorphic variants rs6684209 and rs7521023 of the CASQ2 gene are associated with the severity of CHF and the risk of developing heart rhythm disturbances. With the CT genotype of the rs6684209 variant, diastolic myocardial dysfunction was more common, but the T allele appeared to be protective against the development of heart rhythm disturbances. Carrier genotype GG (rs7521023) is a risk factor for dilatation of the left atrium, which in turn can serve as a substrate for the development of arrhythmias. Acknowledgement/Funding This work was supported in part by the Russian Foundation for Basic Research, No. 17-04-01450 A.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Nakayama ◽  
Y Oshima ◽  
S Kusumoto ◽  
S Osaga ◽  
J Yamamoto ◽  
...  

Abstract Background Anthracycline-induced cardiotoxicity is a serious complication in patients with malignant lymphoma (ML) who received chemotherapy, which threatens life prognosis and quality of life of patients. However, incidence and risk factors of cardiotoxicity in patients with ML who undergo intensive chemotherapy which aims complete remission is not clarified. Furthermore, prognosis after cardiotoxicity and that after recovery from cardiotoxicity have not been elucidated. Method We screened 443 ML patients who received either rituximab (R)-CHOP or CHOP regimen between January 2008 and December 2017 at Nagoya City University Hospital. Two handled forty-four patients who underwent echocardiography before and after chemotherapy were enrolled and data were analyzed retrospectively. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) of 10% or greater and an LVEF was below 50%. Partial recovery was defined as a 5% or more of increase in LVEF and an LVEF was ≥50% after cardiotoxicity. Complete recovery was defined as an increase in LVEF became more than 95% of the baseline value. Patient's basic characteristics, chemotherapeutic regimen, laboratory data, echocardiographic data, and prognosis were collected from the medical records by two cardiologists and two hematologists. Result At baseline, the median age was 71 years, the median cumulative dose of doxorubicin was 302 mg/m2 and the median LVEF was 69%. During the follow-up period, cardiotoxicity was observed in 52 out of 244 patients (21%), 30 patients (12%) had a symptomatic heart failure, and 5 patients died from cardiovascular cause. Thirty-five patients developed cardiotoxicity during the first year of chemotherapy. Multivariate analysis identified that only the baseline LVEF (HR 0.949, 95% CI 0.919–0.981, p=0.002) was an independent risk factor for cardiotoxicity. In our study, patients who received more than 200 mg/m2 of doxorubicin developed cardiotoxicity frequently. Among 52 patients who experienced cardiotoxicity, partial recovery and full recovery were observed in 18 (35%) and 4 (8%) patients, respectively. Four patients without recovery died due to heart failure and 1 patient with partial recovery died suddenly. Six out of 18 patients with partial recovery developed re-cardiotoxicity. Conclusion ML patients who undergo more than 200 mg/m2 of doxorubicin need a watchful follow-up. Only a baseline LVEF was an independent risk factor for cardiotoxicity. one third of patients with partial recovery developed re-cardiotoxicity. Funding Acknowledgement Type of funding source: None


2000 ◽  
Vol 99 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Stephan SCHMIDT-SCHWEDA ◽  
Christian HOLUBARSCH

In the failing human myocardium, both impaired calcium homoeostasis and alterations in the levels of contractile proteins have been observed, which may be responsible for reduced contractility as well as diastolic dysfunction. In addition, levels of a key protein in calcium cycling, i.e. the sarcoplasmic reticulum Ca2+-ATPase, and of the α-myosin heavy chain have been shown to be enhanced by treatment with etomoxir, a carnitine palmitoyltransferase inhibitor, in normal and pressure-overloaded rat myocardium. We therefore studied, for the first time, the influence of long-term oral application of etomoxir on cardiac function in patients with chronic heart failure. A dose of 80 mg of etomoxir was given once daily to 10 patients suffering from heart failure (NYHA functional class II–III; mean age 55±4 years; one patient with ischaemic heart disease and nine patients with dilated idiopathic cardiomyopathy; all male), in addition to standard therapy. The left ventricular ejection fraction was measured echocardiographically before and after a 3-month period of treatment. Central haemodynamics at rest and exercise (supine position bicycle) were defined by means of a pulmonary artery catheter and thermodilution. All 10 patients improved clinically; no patient had to stop taking the study medication because of side effects; and no patient died during the 3-month period. Maximum cardiac output during exercise increased from 9.72±1.25 l/min before to 13.44±1.50 l/min after treatment (P < 0.01); this increase was mainly due to an increased stroke volume [84±7 ml before and 109±9 ml after treatment (P < 0.01)]. Resting heart rate was slightly reduced (not statistically significant). During exercise, for any given heart rate, stroke volume was significantly enhanced (P < 0.05). The left ventricular ejection fraction increased significantly from 21.5±2.6% to 27.0±2.3% (P < 0.01). In acute studies, etomoxir showed neither a positive inotropic effect nor vasodilatory properties. Thus, although the results of this small pilot study are not placebo-controlled, all patients seem to have benefitted from etomoxir treatment. Etomoxir, which has no acute inotropic or vasodilatory properties and is thought to increase gene expression of the sarcoplasmic reticulum Ca2+-ATPase and the α-myosin heavy chain, improved clinical status, central haemodynamics at rest and during exercise, and left ventricular ejection fraction.


Author(s):  
Naila Niaz ◽  
Syed Muhammad Faraz Ali ◽  
Attaullah Younas ◽  
Tallat Anwar Faridi ◽  
Asif Hanif

Despite advancing medical technology, Heart Failure (HF) is still a prevalent disease with high mortality and high health expenditure. To improve patient outcome and prognosis, it is important to identify the association of risk factors which leads to the co-morbid depression and anxiety in heart failure patients. Objectives: To determine the association of depression and/or anxiety with age, gender and ejection fraction in heart failure patients. Methods: It is an analytical cross sectional study including 323 CHF patients who visited the to the Faisalabad Institute of Cardiology hospital Out-Patient Department, 250 were males and 73 were females, mean age was 54.1 ± 9.2 years having 70 years as maximum and 25 years as minimum.  Data collection was done using Hospital Anxiety and Depression Scale (HADS) questionnaire to assess depression and anxiety. Data was analyzed using SPSS version 24. For quantitative data, mean and standard deviation was calculated and for qualitative data frequency and percentages was calculated. To measure the association of anxiety and depression with age categories, ejection fraction and gender, chi square test was used. P values less than and equal to 0.05 were taken as significant. Results: No association of depression and anxiety with gender and Left Ventricular Ejection Fraction (LVEF) was observed. However, depression and anxiety were found to be significantly associated with age Conclusions: The study concluded that age is a strong risk factor of depression and anxiety in congestive heart failure patients. Multidisciplinary health care team approach and interventions are required to cater chronic heart failure (CHF) patients to address the psychological burden.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jwan A Naser ◽  
Sorin Pislaru ◽  
Marius N Stan ◽  
Grace Lin

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.


1995 ◽  
Vol 13 (11) ◽  
pp. 2827-2834 ◽  
Author(s):  
P Anderlini ◽  
R S Benjamin ◽  
F C Wong ◽  
H M Kantarjian ◽  
M Andreeff ◽  
...  

PURPOSE To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.J Lundorff ◽  
M Sengeloev ◽  
S Pedersen ◽  
D Modin ◽  
N.E Bruun ◽  
...  

Abstract Background RV dysfunction is associated with increased mortality and morbidity in patients with heart failure. Due to the complex shape and position of the RV, assessing RV function from echocardiographic images remains a challenge. Purpose We have previously found that global longitudinal strain from 2DSTE is superior to left ventricular ejection fraction (LVEF) in identifying HFrEF patients with high risk of mortality. In this study we wanted to examine RV 2DSTE in patients with HFrEF and compare its prognostic value to conventional RV measures. Methods and results Echocardiographic examinations were retrieved from 701 patients with HFrEF. RV estimates were analysed offline, and end point was all-cause mortality. During follow-up (median 39 months) 118 patients (16.8%) died. RV GLS and RV FWS remained associated with mortality after multivariable adjustment, independent of TAPSE (RV GLS: HR 1.07, 95% CI 1.02–1.13, p=0.010, per 1% decrease) (RV FWS: HR 1.05, 95% CI 1.01–1.09, p=0.010, per 1% decrease). This seemed to be caused by significant associations in men as TAPSE remained as the only independent prognosticator in women. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics (TAPSE: 0.74 to 0.75; RVFAC: 0.74 to 0.75; RVFWS: 0.74 to 0.77; RVGLS: 0.74 to 0.77). Conclusions RV strain from 2DSTE was associated with mortality in patients with HFrEF, independent of TAPSE and established risk factors. Our results indicate that RV strain is particularly valuable in male patients, whereas in women TAPSE remains a stronger prognosticator. RV GLS and the risk of mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PGJ reports receiving lecture fee from Novo Nordisk.


2019 ◽  
Vol 14 (6) ◽  
pp. 870-878 ◽  
Author(s):  
D. S. Novikova ◽  
H. V. Udachkina ◽  
I. G. Kirillova ◽  
T. V. Popkova

Rheumatoid arthritis (RA) is characterized by a twofold increase in morbidity and mortality due to chronic heart failure (CHF). At the same time, the prevalence of CHF among RA patients is significantly underestimated. The aim of the review was to analyze the results of the main studies on the features of the clinical presentation of heart failure (HF) in RA patients, the role of visualization techniques and biomarkers in the diagnosis of HF and preclinical dysfunction of the myocardium. HF in patients with RA is characterized by a predominance of HF with a preserved left ventricular ejection fraction (LVEF). The use of clinical diagnostic criteria in RA patients can lead to both over- or underdiagnosis of CHF. Systolic dysfunction estimated by LVEF is rare in RA and does not reflect the real frequency of myocardial dysfunction. Echocardiography (ECHO-CG) with tissue Doppler echocardiography (TDE) and visualization of myocardial deformation, magnetic resonance imaging (MRI) of the heart in RA patients revealed a high frequency of HF with preserved ejection fraction, left ventricular remodeling and hypertrophy, pre-clinical systolic and diastolic dysfunction. Determination of natriuretic peptides is useful for verifying the diagnosis of HF and estimating the prognosis in this cohort, despite the possible decrease in the sensitivity and specificity of these indicators in RA patients. The review discusses the advantages of MRI of the heart, including quantitative T1 and T2 regimens, in the diagnosis of myocarditis, myocardial fibrosis, and myocardial perfusion disorders in RA patients. In order to verify the diagnosis of heart failure and detect pre-clinical myocardial dysfunction in RA patients, the determination of natriuretic peptides concentration should become part of the routine examination, beginning with the debut of the disease, along with the collection of a cardiological history, physical examination, ECHO-CT with TDE, and visualization of myocardial deformation. Evaluation of the quantitative characteristics of tissue according to MRI of the heart could improve the diagnosis of myocardial damage.


2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Peng Liu ◽  
Quanli Pan

Background. Chronic heart failure (CHF) is a serious heart disease resulting from cardiac dysfunction. Oxidative stress is an important factor in aging and disease. Butein, however, has antioxidant properties. To determine the effect of butein on oxidative stress injury in rats, a CHF rat model was established. Methods. The CHF rat model was induced by abdominal aortic coarctation (AAC). Rats in CHF+butein and sham+butein group were given 100 mg/kg butein via gavage every day to detect the effect of butein on oxidative stress injury and myocardial dysfunction. The cardiac structural and functional parameters, including the left ventricular end-systolic dimension (LVESD), the left ventricular end-diastolic dimension (LVEDD), the left ventricular ejection fraction (LVEF), and the left ventricular fractional shortening (LVFS), were measured. Oxidative stress was measured through the production of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). Cardiac injury markers like creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) were evaluated. Hematoxylin and eosin (H&E) staining was used to observe the myocardial cell morphology. The effect of butein on the extracellular signal-regulated kinase (ERK)/nuclear factor-E2 p45-related factor (Nrf2) signaling was confirmed by Western blot analysis. Results. Butein had a significant effect on CHF in animal models. In detail, butein inhibited oxidative stress, relieved cardiac injury, and alleviated myocardial dysfunction. Importantly, butein activated the ERK1/2 pathway, which contributed to Nrf2 activation and subsequent heme oxygenase-1 (HO-1) and glutathione cysteine ligase regulatory subunit (GCLC) induction. Conclusions. In this study, butein inhibits oxidative stress injury in CHF rat model via ERK/Nrf2 signaling pathway.


Kardiologiia ◽  
2020 ◽  
Vol 60 (5) ◽  
pp. 90-99
Author(s):  
S. K. Stolbova ◽  
N. A. Dragomiretskaya ◽  
I. G. Beliaev ◽  
V. I. Podzolkov

Aim To study clinical and laboratory associations of hepatic fibrosis indexes in patients with decompensated NYHA functional class II-IV chronic heart failure (CHF).Material and methods The study included 128 patients admitted to the cardiological or therapeutic department of the University Clinical Hospital #4 at the I. M. Sechenov First Moscow State Medical University (Sechenov University) with symptoms of CHF associated with ischemic heart disease (IHD) and/or arterial hypertension (AH). All patients had signs of liver disease (liver enlargement on physical examination ± diffuse changes in hepatic tissue according to ultrasound data). Mean age was 70.59±10.71 years. Along with general clinical examination, severity of hepatic fibrosis was evaluated by calculated indexes, FIB-4, APRI, MELD-XI, and BARD. All calculations were based on laboratory data obtained within the first two days of hospitalization for decompensated CHF, at the onset of active therapy with intravenous diuretics. Statistical analyses were performed with the R programming language (3.6.1).Results In patients with NYHA FC II–IV CHF, the FIB-4 index significantly increased with the increase in NYHA FC (р<0.05). Also, the high liver density by most fibrosis indexes correlated with the probability of LV EF decrease to <40 % (FIB-4: RR, 1.32 at 95 % CI from 0.53 to 3.28, р=0.079; MELD-XI: RR, 1.62 at 95 % CI from 1.19 to 2.20, р=0.004; BARD: median LV EF, 42.5 % vs. 56 %, р=0.019), and a tendency to heart rhythm disorders was observed (FIB-4: RR, 1.92 at 95 % CI from 0.75 to 4.90, р=0.218; BARD: RR, 1.09 at 95 % CI from 0.97 to 1.22, р=0.174; MELD-XI: RR, 1.34 at 95 % CI from 0.94 to 1.90, р=0.101). Increases in liver fibrosis indexes correlated with other multiorgan disorders in CHF patients evident as a decrease in platelet count (FIB-4: р<0.01; APRI: р=0.045) and a tendency to a decrease in hemoglobin (FIB-4: 127 g/l vs. 137 g/l, p=0.249; APRI: 127 g/l vs. 136 g/l, p=0.749). Patients with a high liver density more frequently had cardiorenal syndrome diagnosed by reduced glomerular filtration rate (GFR) estimated by CKD-EPI to less than 60 ml/min / 1.73 m2 (FIB-4: р<0.03; MELD-XI: p=0.0001; BARD: р=0.005). In comparing liver fibrosis indexes in subgroups of CHF patients with preserved and reduced left ventricular ejection fraction (LV EF), significant differences were found only for MELD-XI (12.08 vs. 9.32, р=0.001).Conclusions For all studied indexes, correlations were observed with LV EF, decreases in hemoglobin, and incidence of heart rhythm disorders. For the BARD, FIB-4, and MELD-XI indexes, high results of calculations correlated with the presence of other predictors for unfavorable prognosis and disease severity (LV EF, NYHA FC, presence of type 2 diabetes mellitus, chronic kidney disease, and lower GFR). Liver fibrosis indexes are a new and promising but understudied instrument for evaluation of prognosis in CHF patients, which requires further study to determine most appropriate prognostic formulas.


Sign in / Sign up

Export Citation Format

Share Document