| 1. |
- Babu-Narayan, Sonya V, et al.
(author)
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Dyssynchrony and electromechanical delay are associated with focal fibrosis in the systemic right ventricle - Insights from echocardiography.
- 2016
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 220, s. 382-388
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Journal article (peer-reviewed)abstract
- BACKGROUND: Systemic right ventricular (RV) dysfunction and sudden cardiac death remain problematic late after Mustard operation for transposition of the great arteries. The exact mechanism for that relationship is likely to be multifactorial including myocardial fibrosis. Doppler echocardiography gives further insights into the role of fibrosis shown by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in late morbidity.METHODS AND RESULTS: Twenty-two consecutive patients, mean age 28±8years, were studied with 2D echocardiography, and also assessed by LGE CMR. The presence of LGE in 13/22 patients (59%) was related to delayed septal shortening and lengthening (P=0.002 &P=0.049), prolonged systemic RV isovolumic contraction time (P=0.024) and reduced systemic RV free wall and septal excursion (P=0.027 &P=0.005). The systemic RV total isovolumic time was prolonged but not related to extent of LGE. LGE extent was related to markers of electromechanical delay and dyssynchrony (delayed onset of RV free wall shortening and lengthening; r=0.73 &P=0.004 and r=0.62 &P=0.041, respectively, and QRS duration r=0.68, P<0.01) and was inversely related to systolic RV free wall shortening velocity (r=-0.59 &P=0.042). The presence of LGE was also related to lower exercise capacity, ≥mild tricuspid regurgitation and more arrhythmia (P=0.008, P=0.014 and P=0.040). RV free wall excursion and systolic tissue Doppler velocity were related to CMR derived RV ejection fraction (r=0.51, P=0.015, and r=0.77, P=<0.001, respectively).CONCLUSION: Post Mustard repair, myocardial fibrosis is related to dyssynchrony, RV long axis dysfunction and tricuspid regurgitation. Echocardiographic measurements of systemic RV function can be confidently used in serial follow-up following Mustard operation.
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| 2. |
- Daelman, Bo, et al.
(author)
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Frailty and cognitive function in middle-aged and older adults with congenital heart disease
- 2024
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
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Journal article (peer-reviewed)abstract
- Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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| 3. |
- Diller, Gerhard-Paul, et al.
(author)
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Exercise intolerance in adult congenital heart disease : comparative severity, correlates, and prognostic implication.
- 2005
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In: Circulation. - 0009-7322 .- 1524-4539. ; 112:6, s. 828-35
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although some patients with adult congenital heart disease (ACHD) report limitations in exercise capacity, we hypothesized that depressed exercise capacity may be more widespread than superficially evident during clinical consultation and could be a means of assessing risk.METHODS AND RESULTS: Cardiopulmonary exercise testing was performed in 335 consecutive ACHD patients (age, 33+/-13 years), 40 non-congenital heart failure patients (age, 58+/-15 years), and 11 young (age, 29+/-5 years) and 12 older (age, 59+/-9 years) healthy subjects. Peak oxygen consumption (peak VO2) was reduced in ACHD patients compared with healthy subjects of similar age (21.7+/-8.5 versus 45.1+/-8.6; P<0.001). No significant difference in peak VO2 was found between ACHD and heart failure patients of corresponding NYHA class (P=NS for each NYHA class). Within ACHD subgroups, peak VO2 gradually declined from aortic coarctation (28.7+/-10.4) to Eisenmenger (11.5+/-3.6) patients (P<0.001). Multivariable correlates of peak VO2 were peak heart rate (r=0.33), forced expiratory volume (r=0.33), pulmonary hypertension (r=-0.26), gender (r=-0.23), and body mass index (r=-0.19). After a median follow-up of 10 months, 62 patients (18.5%) were hospitalized or had died. On multivariable Cox analysis, peak VO2 predicted hospitalization or death (hazard ratio, 0.937; P=0.01) and was related to the frequency and duration of hospitalization (P=0.01 for each).CONCLUSIONS: Exercise capacity is depressed in ACHD patients (even in allegedly asymptomatic patients) on a par with chronic heart failure subjects. Lack of heart rate response to exercise, pulmonary arterial hypertension, and impaired pulmonary function are important correlates of exercise capacity, as is underlying cardiac anatomy. Poor exercise capacity identifies ACHD patients at risk for hospitalization or death.
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| 4. |
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| 5. |
- Gambarotta, Agostino, et al.
(author)
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Editorial : Smart Energy Systems
- 2022
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In: FRONTIERS IN MECHANICAL ENGINEERING-SWITZERLAND. - : FRONTIERS MEDIA SA. - 2297-3079. ; 8
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Journal article (other academic/artistic)
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| 6. |
- Hjortshøj, Cristel M Sørensen, et al.
(author)
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Past and current cause-specific mortality in Eisenmenger syndrome.
- 2017
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:26, s. 2060-2067
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Journal article (peer-reviewed)abstract
- Aims: Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015.Methods and results: This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 ± 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001).Conclusion: The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly needed.
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| 7. |
- Terpos, Evangelos, et al.
(author)
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Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post-bortezomib monotherapy
- 2011
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 131:6, s. 1466-1471
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Journal article (peer-reviewed)abstract
- Sclerostin is a Wingless and Int-1 inhibitor, which is produced by osteocytes and inhibits osteoblast-driven bone formation. Sclerostin is implicated in the pathogenesis of bone loss in metabolic bone disorders but there is no information for its effect on multiple myeloma (MM)-related osteolytic disease. We evaluated circulating sclerostin in 157 newly diagnosed patients with symptomatic myeloma, in 25 with relapsed myeloma who received bortezomib monotherapy, in 21 patients with monoclonal gammopathy of undetermined significance (MGUS), and in 21 healthy controls. Patients with active myeloma had elevated circulating sclerostin compared to MGUS patients and controls (p < 0.01). MM patients who presented with fractures at diagnosis (n = 34) had very high levels of circulating sclerostin compared with all others (p < 0.01), whereas sclerostin correlated negatively with bone specific alkaline phosphatase (a bone formation marker; r = -0.541, p < 0.0001) and positively with C-telopeptide of collagen type-1 (a bone resorption marker; r = 0.524, p < 0.0001). Patients with International Staging System (ISS)-3 disease had higher circulating sclerostin compared to ISS-1 and ISS-2 MM (p = 0.001). Furthermore, patients with high sclerostin (upper quartile, n = 40) had a median survival of 27 months versus 98 months of all others (p = 0.031). Relapsed MM patients had higher levels of circulating sclerostin even compared to newly diagnosed patients (p < 0.01). Bortezomib monotherapy resulted in a reduction of sclerostin by almost 50% in both responders and non-responders. These results suggest that patients with active myeloma have elevated circulating sclerostin, which correlated with advanced disease features including severe bone disease. Our study indicates sclerostin as a possible target for the development of novel therapies to enhance osteoblast function in myeloma.
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| 8. |
- Terpos, Evangelos, et al.
(author)
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High Serum Sclerostin Correlates with Advanced Stage, Increased Bone Resorption, Reduced Osteoblast Function, and Poor Survival in Newly-Diagnosed Patients with Multiple Myeloma.
- 2009
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:22, s. 425-425
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is characterized by the presence of lytic bone disease due to increased osteoclast activity which is accompanied by reduced osteoblast function. To-date dickkopf-1 (Dkk-1) is considered as the main osteoblast inhibitor which is overproduced by myeloma cells and inhibits Wnt signaling leading to osteoblast exhaustion. Sclerostin is another canonical Wnt antagonist through its binding to low-density lipoprotein-receptor-related protein 5/6. Sclerostin is specifically expressed by osteocytes and inhibits bone morphogenic protein-induced osteoblast differentiation and ectopic bone formation. Osteonectin (SPARC) is a multi-faceted protein that belongs to a family of matricellular proteins. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. SPARC shows affinity for collagen in addition to bone mineral calcium. The aim of this study contacted by the Greek Myeloma Study Group in collaboration with Biomarker Design Forschungs GmbH (BDF), Vienna, Austria was to evaluate, for the first time in the literature, the serum levels of sclerostin in patients with MM and explore possible correlations with clinical and laboratory data, including SPARC levels, ISS stage and survival. One hundred and fifty-seven patients (87M/70F, median age 68 years) with MM at diagnosis before the administration of any type of therapy, including bisphosphonates, were evaluated. Serum sclerostin and SPARC were measured using an ELISA methodology developed by BDF for Biomedica Medizinprodukte GmbH & Co KG (Vienna, Austria). Both assays are sandwich type ELISA using biotinylated antibodies/HRP-streptavidine for the detection of sclerostin and SPARC in the serum. The detection limit of the sclerostin ELISA was 0.18 ng/ml and the coefficient of variation (CV) 6%. The standard range was set from 0.3-3 ng/ml. For the SPARC ELISA we found a detection limit of 1.95 ng/ml and CVs of 8% using a standard range from 5-130 ng/ml. Serum sclerostin and SPARC were determined in MM patients, 21 patients with MGUS and 21 healthy controls, of similar gender and age. Bone remodeling was also studied by the measurement of a series of serum indices within one week from diagnosis: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)], ii) Dkk-1, iii) bone resorption markers [C-terminal cross-linking telopeptide of collagen type-I (CTX) and 5b-isoenzyme of tartrate resistant acid phosphatase (TRACP-5b)], and iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin (OC)]. Patients with MM had increased levels of serum sclerostin compared with MGUS patients (mean value±SD: 0.48±0.46 vs. 0.26±0.29 ng/ml; p=0.004) and healthy controls (0.31±0.20 ng/ml, p=0.01). In contrast, both patients with MM and MGUS had reduced levels of serum SPARC (26.3±16.2 and 27.2±18.0 ng/ml, respectively) compared to controls (52.8±50.2 ng/ml; p<0.001). Sclerostin values strongly correlated with beta2-microglobulin (r=0.354, p<0.0001), cystatin-C (r=0.389, p<0.0001), serum creatinine (r=0.380, p<0.0001), and bALP (r=-0.541, p<0.0001). No correlations were observed between sclerostin with sRANKL, OPG, Dkk-1 or SPARC. Patients with advanced bone disease assessed by conventional radiography (>3 lytic lesions and/or a pathological fracture) had a borderline increase of sclerostin compared to all others (median value: 0.51 vs. 0.41 ng/ml, p=0.09). Patients with ISS-3 disease had increased levels of sclerostin compared to patients with ISS-1 and ISS-2 MM (ANOVA p=0.001). Median survival of MM patients was 48 months and median follow-up period was 20 months. Patients who had a serum sclerostin of ≥0.62 ng/ml (upper quartile, n=40 patients) had a median survival of 27 months, while median survival of all other patients was 98 months (p=0.031). In conclusion, our study provided evidence that sclerostin is increased in the serum of patients with MM and correlates with advanced ISS stage, increased bone resorption, reduced osteoblast function and poor survival. SPARC is reduced in MM possibly confirming the reduced osteoblast function observed in these patients. Sclerostin seems to participate in the biology of MM and thus it may be a possible target for the development of novel therapies that can both increase osteoblast function and target myeloma cells.
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