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Factors associated with baseline and serial changes in circulating NT-proBNP and high-sensitivity cardiac troponin T in a population-based cohort (Dallas Heart Study).
Puleo, CW, Ayers, CR, Garg, S, Neeland, IJ, Lewis, AA, Pandey, A, Drazner, MH, de Lemos, JA
Biomarkers in medicine. 2021;(16):1487-1498
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Abstract
Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) associate with structural heart disease and heart failure risk in individuals without known cardiovascular disease (CVD). However, few data are available regarding whether factors influencing levels of these two biomarkers are similar or distinct. We performed serial measurement of NT-proBNP and hs-cTnT in a contemporary multiethnic cohort with extensive phenotyping, with the goal of identifying their respective biological determinants in a population without known or suspected CVD. Methods: We evaluated 1877 participants of the Dallas Heart Study who had NT-proBNP and hs-cTnT measured and were free from clinical CVD at the each of its two examinations (2000-2002 and 2007-2009). Variables collected included demographic and risk factors, high-sensitivity C-reactive protein, body composition via dual-energy x-ray absorptiometry, coronary artery calcium by computed tomography, and cardiac dimensions and function by cardiac MRI. Linear regression was used to identify associations of these factors with each biomarker at baseline and with changes in biomarkers over follow-up. Results: NT-proBNP and hs-cTnT were poorly correlated at baseline (Spearman rho 0.083, p = 0.015), with only moderate correlation between change values (rho 0.18, p < 0.001). hs-cTnT positively associated and NT-proBNP inversely associated with male gender and black race. At baseline, both NT-proBNP and hs-cTnT associated with left ventricular end-diastolic volume and wall thickness, but only NT-proBNP associated with left atrial size. Changes in cardiac dimensions between phases were more strongly associated with changes in NT-proBNP than hs-cTnT. NT-proBNP was more strongly associated with high-sensitivity C-reactive protein and measures of body composition than hs-cTnT. Conclusion: Among individuals without CVD in the general population, NT-proBNP and hs-cTnT are nonredundant biomarkers that are differentially associated with demographic and cardiac factors. These findings indicate that hs-cTnT and NT-proBNP may reflect different pathophysiological pathways.
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Blood Plasma's Protective Ability against the Degradation of S-Nitrosoglutathione under the Influence of Air-Pollution-Derived Metal Ions in Patients with Exacerbation of Heart Failure and Coronary Artery Disease.
Wądołek, A, Drwiła, D, Oszajca, M, Stochel, G, Konduracka, E, Brindell, M
International journal of molecular sciences. 2021;(19)
Abstract
One of the consequences of long-term exposure to air pollutants is increased mortality and deterioration of life parameters, especially among people diagnosed with cardiovascular diseases (CVD) or impaired respiratory system. Aqueous soluble inorganic components of airborne particulate matter containing redox-active transition metal ions affect the stability of S-nitrosothiols and disrupt the balance in the homeostasis of nitric oxide. Blood plasma's protective ability against the decomposition of S-nitrosoglutathione (GSNO) under the influence of aqueous PM extract among patients with exacerbation of heart failure and coronary artery disease was studied and compared with a group of healthy volunteers. In the environment of CVD patients' plasma, NO release from GSNO was facilitated compared to the plasma of healthy controls, and the addition of ascorbic acid boosted this process. Model studies with albumin revealed that the amount of free thiol groups is one of the crucial factors in GSNO decomposition. The correlation between the concentration of NO released and -SH level in blood plasma supports this conclusion. Complementary studies on gamma-glutamyltranspeptidase activity and ICP-MS multielement analysis of CVD patients' plasma samples in comparison to a healthy control group provide broader insights into the mechanism of cardiovascular risk development induced by air pollution.
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Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM with heart failure.
Vanninen, SUM, Leivo, K, Seppälä, EH, Aalto-Setälä, K, Pitkänen, O, Suursalmi, P, Annala, AP, Anttila, I, Alastalo, TP, Myllykangas, S, et al
PloS one. 2018;(9):e0203422
Abstract
During the last two decades, mutations in sarcomere genes have found to comprise the most common cause for hypertrophic cardiomyopathy (HCM), but still significant number of patients with dominant HCM in the family are left without molecular genetic diagnosis. Next generation sequencing (NGS) does not only enable evaluation of established HCM genes but also candidate genes for cardiomyopathy are frequently tested which may lead to a situation where conclusive interpretation of the variant requires extensive family studies. We aimed to characterize the phenotype related to a variant in the junctophilin-2 (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we did extensive review of the literature and databases about JPH2 variation in association with cardiac disease. We characterize nine Finnish index patients with HCM and heterozygous for JPH2 c.482C>A, p.(Thr161Lys) variant were included and segregation studies were performed. We identified 20 individuals affected with HCM with or without systolic heart failure and conduction abnormalities in the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26 heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age 80. Co-segregation of the variant with HCM phenotype was observed in six families. Main clinical features were left ventricular hypertrophy, arrhythmia vulnerability and conduction abnormalities including third degree AV-block. In some patients end-stage severe left ventricular heart failure with normal or mildly enlarged diastolic dimensions was detected. In conclusion, we propose that the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing atypical HCM.
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Beneficial effects of the treatment of iron deficiency on clinical condition, left ventricular function, and quality of life in patients with chronic heart failure.
Mirdamadi, A, Arefeh, A, Garakyaraghi, M, Pourmoghadas, A
Acta bio-medica : Atenei Parmensis. 2018;(2):214-218
Abstract
BACKGROUND Anemia is now considered as an important contributing factor to the deterioration of chronic heart failure. The present study aimed to assess the effects of intravenous iron therapy on clinical condition, left ventricular function and also quality of life in patients who suffered of chronic heart failure and concomitant iron deficiency. METHODS In this clinical trial, 25 consecutive patients with concomitant chronic heart failure and iron deficiency referred to Shariati hospital in Isfahan, Iran in 2013. After initial clinical, laboratory, and echocardiography assessments, the patients administered 200 mg intravenous Iron per week until compensating iron deficit. Then, all study parameters were assessed again and compared to parameters before the therapeutic intervention. RESULTS The NYHA class showed a significant improvement after the therapeutic approach. The prevalence of heart failure-related edema was also significantly reduced from 60% before treatment to 48% after that (p = 0.036). The rate of hospitalization was considerably reduced from 42% to 16% (P < 0.001). Moreover, mean 6 minute walk test (6MWT) was increased from 155.18 m to 187.40 m (P < 0.001). Comparing Left Ventricular Ejection Fraction (LVEF) after treatment to figures before the test indicated a significant improvement in this parameter (27.5% versus 33.0%, P = 0.007). The treatment of iron deficiency in this group of subjects got a significant improvement in SF36 total score. CONCLUSION In patients with chronic heart failure, the treatment of iron deficiency results in a marked improvement in functional status, ejection fraction, and also quality of life as well as a reduction in need to re-hospitalization, however renal function was deteriorated and thus more pay attention to renal function is necessary.
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Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial.
Anker, SD, Kosiborod, M, Zannad, F, Piña, IL, McCullough, PA, Filippatos, G, van der Meer, P, Ponikowski, P, Rasmussen, HS, Lavin, PT, et al
European journal of heart failure. 2015;(10):1050-6
Abstract
AIMS: Hyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS-9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZE--a Phase 3, double-blind, randomized, placebo-controlled trial. In the present study we evaluated management of serum potassium with daily ZS-9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies. METHODS AND RESULTS Heart failure patients with evidence of hyperkalaemia (serum potassium ≥5.1 mmol/L, n = 94) were treated with open-label ZS-9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5-5.0 mmol/L) were randomized to daily ZS-9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8-29 post-randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS-9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P<0.01 vs. each ZS-9 group); greater proportions of ZS-9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P < 0.01 vs. each ZS-9 group). The safety profile was consistent with previously reported overall study population. CONCLUSION Compared with placebo, all three ZS-9 doses lowered potassium and effectively maintained normokalaemia for 28 days in heart failure patients without adjusting concomitant RAASi, while maintaining a safety profile consistent with the overall study population.
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Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden.
Hofmarcher, T, Borg, S
Journal of medical economics. 2015;(7):492-501
Abstract
OBJECTIVE Iron deficiency is a common but treatable comorbidity in chronic heart failure (CHF) that is associated with impaired health-related quality-of-life (HRQoL). This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose (FCM) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective. METHODS A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo. Data on health outcomes and medical resource use were mainly taken from the FAIR-HF trial and combined with Swedish cost data. An incremental cost-effectiveness ratio (ICER) was calculated as well as the change in per-patient costs for primary care and hospital care. RESULTS In the FCM group compared with placebo, quality-adjusted life years (QALYs) are higher (difference = 0.037 QALYs), but so are per-patient costs [(difference = SEK 2789 (€303)]. Primary care and hospital care equally share the additional costs, but within hospitals there is a major shift of costs from inpatient care to outpatient care. The ICER is SEK 75,389 (€8194) per QALY. The robustness of the result is supported by sensitivity analyses. CONCLUSIONS Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective. The ICER in the base case scenario is twice as high as previously thought, but noticeably below SEK 500,000 (€54,300) per QALY, an informal average reference value used by the Swedish Dental and Pharmaceutical Benefits Agency. Increased HRQoL and fewer hospitalizations are the key drivers of this result.
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High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study.
Angadi, SS, Mookadam, F, Lee, CD, Tucker, WJ, Haykowsky, MJ, Gaesser, GA
Journal of applied physiology (Bethesda, Md. : 1985). 2015;(6):753-8
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Exercise training is an established adjuvant therapy in heart failure; however, the effects of high-intensity interval training (HIIT) in HFpEF are unknown. We compared the effects of HIIT vs. moderate-intensity aerobic continuous training (MI-ACT) on peak oxygen uptake (V̇o₂peak), left ventricular diastolic dysfunction, and endothelial function in patients with HFpEF. Nineteen patients with HFpEF (age 70 ± 8.3 yr) were randomized to either HIIT (4 × 4 min at 85-90% peak heart rate, with 3 min active recovery) or MI-ACT (30 min at 70% peak heart rate). Fifteen patients completed exercise training (HIIT: n = 9; MI-ACT: n = 6). Patients trained 3 days/wk for 4 wk. Before and after training patients underwent a treadmill test for V̇o₂peak determination, 2D-echocardiography for assessment of left ventricular diastolic dysfunction, and brachial artery flow-mediated dilation (FMD) for assessment of endothelial function. HIIT improved V̇o₂peak (pre = 19.2 ± 5.2 ml·kg(-1)·min(-1); post = 21.0 ± 5.2 ml·kg(-1)·min(-1); P = 0.04) and left ventricular diastolic dysfunction grade (pre = 2.1 ± 0.3; post = 1.3 ± 0.7; P = 0.02), but FMD was unchanged (pre = 6.9 ± 3.7%; post = 7.0 ± 4.2%). No changes were observed following MI-ACT. A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT (-3.3 ± 6.6 vs. +5.8 ± 10.7 ml/m(2); P = 0.06). In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction. HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF.
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Efficacy of thyroid blockade on thyroid radioiodine uptake in 123I-mIBG imaging.
Friedman, NC, Hassan, A, Grady, E, Matsuoka, DT, Jacobson, AF
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2014;(2):211-5
Abstract
UNLABELLED Although iodinated radiopharmaceuticals usually contain a small quantity of unbound iodine, it is difficult to establish the degree to which thyroid activity on scintigraphic images reflects uptake of free radioiodine. The objective of the present study was to examine the effectiveness of thyroid blockade in subjects undergoing (123)I-meta-iodobenzylguanidine (mIBG) imaging and to estimate the relative contribution of bound and unbound radioiodine to imaging findings. METHODS All subjects were participants in prospective trials of (123)I-mIBG cardiac imaging in which pretreatment with thyroid blockade was optional unless locally required. In a pilot project, 15 subjects (6 blocked) had thyroid uptake measured at 4 h using a probe system. Fifteen-minute (early) and 4-h (late) anterior planar chest images that included the thyroid region were visually scored for thyroid uptake (scale of 0-4) in another group of 152 subjects (98 blocked). Quantitative analysis based on thyroid regions of interest was performed on anterior planar images from a further sample of 669 subjects (442 blocked). For all 3 investigations, quantitative comparisons of thyroid uptake were made between the blocked and nonblocked subjects. RESULTS There was no statistical difference between probe uptake of the 6 blocked and 9 nonblocked subjects. However, in the second series, mean visual score on the late images was significantly lower for blocked than nonblocked subjects (P < 0.001). In the region-of-interest analyses, net thyroid counts were significantly higher on the late images of nonblocked subjects (P < 0.0001), and compared with early images, 87% of subjects who received blockade showed decreased or unchanged counts whereas 75% of nonblocked subjects had increased net thyroid activity. In nonblocked subjects, an estimated 79% of thyroid counts on late images could be attributed to unbound (123)I. CONCLUSION On the basis of 3 different methods for assessing thyroid uptake of (123)I, use of thyroid blockade pretreatment in (123)I-mIBG imaging prevents increase of thyroid activity over time because of uptake of unbound (123)I. In most subjects, there is a low level of (123)I-mIBG thyroid activity that probably represents specific uptake in sympathetic nerve terminals.
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Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b).
Greenberg, B, Yaroshinsky, A, Zsebo, KM, Butler, J, Felker, GM, Voors, AA, Rudy, JJ, Wagner, K, Hajjar, RJ
JACC. Heart failure. 2014;(1):84-92
Abstract
OBJECTIVES Impaired cardiac isoform of sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) activity is a key abnormality in heart failure patients with reduced ejection fraction. The CUPID 2 (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b) trial is designed to evaluate whether increasing SERCA2a activity via gene therapy improves clinical outcome in these patients. BACKGROUND Intracoronary delivery of recombinant adeno-associated virus serotype 1 (AAV1)/SERCA2a improves intracellular Ca(2+) handling by increasing SERCA2a protein levels and, as a consequence, restores systolic and diastolic function. In a previous phase 2a trial, this therapy improved symptoms, functional status, biomarkers, and left ventricular function, and reduced cardiovascular events in advanced heart failure patients. METHODS CUPID 2 is a phase 2b, double-blind, placebo-controlled, multinational, multicenter, randomized event-driven study in up to 250 patients with moderate-to-severe heart failure with reduced ejection fraction and New York Heart Association functional class II to IV symptoms despite optimal therapy. Enrolled patients will be at high risk for recurrent heart-failure hospitalizations by virtue of having elevated N-terminal pro-B-type natriuretic peptide/BNP (>1,200 pg/ml, or >1,600 pg/ml if atrial fibrillation is present) and/or recent heart failure hospitalization. The primary endpoint of time-to-recurrent event (heart failure-related hospitalizations in the presence of terminal events [all-cause death, heart transplant, left ventricular assist device implantation or ambulatory worsening heart failure]) will be assessed using the joint frailty model. This ongoing trial is expected to complete recruitment in 2014, with the required number of 186 recurrent events estimated to occur by mid 2015. RESULTS Available data indicate that calcium up-regulation by AAV1/SERCA2a gene therapy is safe and of potential benefit in advanced heart failure patients. CONCLUSIONS The CUPID 2 trial is designed to study the effects of this therapy on clinical outcome in these patients. (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b [CUPID-2b]; NCT01643330).
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Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome--an analysis from RELAX-AHF.
Voors, AA, Davison, BA, Teerlink, JR, Felker, GM, Cotter, G, Filippatos, G, Greenberg, BH, Pang, PS, Levin, B, Hua, TA, et al
European journal of heart failure. 2014;(11):1230-40
Abstract
AIMS: We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40 mg] + [(total oral dose)/80 mg)] furosemide (or equivalent loop diuretic dose) up to day 5. Median diuretic response was -0.42 (-1.00, -0.14) kg/40 mg. A poor diuretic response was independently associated with Western-like region (Western Europe, North America, Israel, and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels of aspartate aminotransferase and potassium (all P < 0.01). Randomization to serelaxin was associated with lower doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue scale (VAS) at day 5 (primary endpoint; P = 0.0002), and with a higher risk of cardiovascular death or rehospitalization for heart failure or renal failure through day 60 (secondary endpoint, P < 0.0001), but not with increased 180-day cardiovascular mortality (P = 0.507). CONCLUSIONS In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response. TRIAL REGISTRATION NCT00520806.