scholarly journals Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy

Author(s):  
Guixin Wu ◽  
Jie Liu ◽  
Minghao Liu ◽  
Qiya Huang ◽  
Jieyun Ruan ◽  
...  

Background: The presence of variants in OBSCN was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether OBSCN truncating variants were associated with HCM remained unknown. Methods: Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for OBSCN truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the OBSCN truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained. Results: There were 28 qualifying truncating variants in the OBSCN gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The OBSCN truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4, P =0.004). This association was confirmed in the replication cohort (odds ratio, 3.8, P =0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 ( P <0.001). Patients with or without OBSCN truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with OBSCN truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40–6.70], P =0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21–5.71], P =0.015). Conclusions: Our data indicated that OBSCN truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.

2021 ◽  
Vol 10 (7) ◽  
pp. 1347
Author(s):  
Quirino Ciampi ◽  
Iacopo Olivotto ◽  
Jesus Peteiro ◽  
Maria D’Alfonso ◽  
Fabio Mori ◽  
...  

Background: Sympathetic dysfunction can be evaluated by heart rate reserve (HRR) with exercise test. Objectives: To determine the value of HRR in predicting outcome of patients with hypertrophic cardiomyopathy (HCM). Methods: We enrolled 917 HCM patients (age = 49 ± 15 years, 516 men) assessed with exercise stress echocardiography (ESE) in 11 centres. ESE modality was semi-supine bicycle in 51 patients (6%), upright bicycle in 476 (52%), and treadmill in 390 (42%). During ESE, we assessed left ventricular outflow tract obstruction (LVOTO), stress-induced new regional wall motion abnormalities (RWMA), and HRR (peak/rest heart rate, HR). By selection, all patients completed the follow-up. Mortality was the predetermined outcome measure Results: During ESE, RWMA occurred in 22 patients (2.4%) and LVOTO (≥50 mmHg) in 281 (30.4%). HRR was 1.90 ± 0.40 (lowest quartile ≤ 1.61, highest quartile > 2.13). Higher resting heart rate (odds ratio 1.027, 95% CI: 1.018–1.036, p < 0.001), older age (odds ratio 1.021, 95% CI: 1.009–1.033, p < 0.001), lower exercise tolerance (mets, odds ratio 0.761, 95% CI: 0.708–0.817, p < 0.001) and resting LVOTO (odds ratio 1.504, 95% CI: 1.043–2.170, p = 0.029) predicted a reduced HRR. During a median follow-up of 89 months (interquartile range: 36–145 months), 90 all-cause deaths occurred. At multivariable analysis, lowest quartile HRR (Hazard ratio 2.354, 95% CI 1.116–4.968 p = 0.025) and RWMA (Hazard ratio 3.279, 95% CI 1.441–7.461 p = 0.004) independently predicted death, in addition to age (Hazard ratio 1.064, 95% CI 1.043–1.085 p < 0.001) and maximal wall thickness (Hazard ratio 1.081, 95% CI 1.037–1.128, p < 0.001). Conclusions: A blunted HRR during ESE predicts survival independently of RWMA in HCM patients.


2017 ◽  
Vol 49 (2) ◽  
pp. 1601592 ◽  
Author(s):  
Helen E. Jo ◽  
Ian Glaspole ◽  
Christopher Grainge ◽  
Nicole Goh ◽  
Peter M.A. Hopkins ◽  
...  

The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25–63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months–4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33–6.47, p<0.001) were strong predictors of mortality. Patients receiving anti-fibrotic medications had better survival (hazard ratio 0.56, 95% CI 0.34–0.92, p=0.022) than those not on anti-fibrotic medications, independent of underlying disease severity.The AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.


2018 ◽  
Vol 27 (7) ◽  
pp. 758-766 ◽  
Author(s):  
Akiko Sakaue ◽  
Hisashi Adachi ◽  
Mika Enomoto ◽  
Ako Fukami ◽  
Eita Kumagai ◽  
...  

Aims It is well known that a decline in physical activity is associated with an increase of all-cause death including cardiovascular events and cancer. Few studies have examined the association between occupational sitting time and mortality. Therefore, we investigated this issue in a general population. Methods Physical activity and occupational sitting time were measured using the Baecke physical activity questionnaire in 1999. The questionnaire generated indices in three physical activity categories: work, sport and leisure-time. A total physical activity index was calculated by adding these three indices. The Baecke physical activity questionnaire was able to evaluate occupational sitting time. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard regression models. Results We enrolled a total of 1680 participants, who were followed up for 15.9 ± 3.8 years. The final follow-up rate was 93%. During the follow-up period, 397 subjects died. A significant inverse association ( p < 0.0001) was found between physical activity and mortality after adjustment for age and sex. Compared with lower levels of physical activity, the adjusted hazard ratio for mortality at higher levels of physical activity was 0.85 (95% CI: 0.78–0.92). Longer occupational sitting time was also significantly associated with higher mortality ( p < 0.01). The adjusted hazard ratio for mortality at longer occupational sitting time was 1.16 (95% CI: 1.05–1.27). These findings were observed in males, but not in females. Conclusions Our data demonstrated that higher levels of physical activity are associated with a reduced risk of cancer and cardiovascular death. Further, longer occupational sitting time is associated with increased mortality.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Bodin ◽  
A Bisson ◽  
B Pierre ◽  
J Herbert ◽  
N Clementy ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction / Background Subcutaneous implantable cardioverter–defibrillators (S-ICD) was designed to avoid complications of single-chamber transvenous implantable cardioverter-defibrillators (VVI ICD) by using an entirely extra-thoracic placement. Purpose Our objective was to compare outcomes following first VVI ICD or S-ICD implantation in an exhaustive nationwide matched cohort. Methods This French longitudinal cohort study was based on the national hospitalization database covering hospital care from for the entire population. All adults (age ≥18 years) hospitalized in French hospitals From January 1, 2010 to September 1, 2020, who underwent a VVI ICD or S-ICD implantation were included. Patients with a previous pacemaker or ICD or with a history of infective endocarditis were excluded. Multivariable analyses for clinical outcomes during the whole follow-up in the groups of interests were performed using a Cox model with all baseline characteristics and reporting hazard ratio. Owing to the non-randomized nature of the study, and considering for significant differences in baseline characteristics, propensity-score matching was also used to control for potential confounders of the treatment outcome relationship. Results 21,667 patients were included in the cohort, 19,493 patients had a transvenous VVI ICD and 2,174 had a subcutaneous ICD. Mean age was 61.2 ± 13.2 years in the VVI ICD group and 52.3 ± 17.5 years in the S-ICD goup. Coronary artery disease was present in 71.6% of patients with a VVI ICD and 48.2% of patients with a S-ICD. Mean follow-up was 28.8 ± 31.8 months. S-ICD patients had a significant higher rate of all-cause death (HR: 1.684, 95%CI: 1.309-2.165, p &lt; 0.001). There were no significant differences in cardiovascular death (HR: 1.092, 95%CI: 0.697-1.711, p = 0.70) and infective endocarditis (HR: 0.354, 95%CI: 0.067-1.433, p = 0.15) between the two groups Using propensity score, 1,582 patients with VVI ICD were matched 1:1 with S-ICD patients. Mean follow-up was 4.5 ± 7.2 months. In the matched analysis, there were no significant differences in all-cause death (HR: 1.090, 95%CI: 0.728-1.633, p = 0.68) and cardiovascular death (HR: 1.167, 95%CI: 0.603-2.260, p = 0.65) between the two groups. A trend toward a lower risk of infective endocarditis in the S-ICD group was also observed without reaching significance (HR : 0.219, 95%CI: 0.047-1.017, p = 0.053). A sensitivity analysis in patients with coronary artery disease in the matched cohort was performed. Same trends were observed without significant differences in all-cause death and cardiovascular death. Conclusion Our nationwide study highlighted a higher risk of all-cause death in patients treated with subcutaneous which however was not statistically significant after propensity score matching. No differences regarding cardiovascular mortality was found. An interesting trend toward diminution of infective endocarditis was also observed without reaching significancy.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Weeranun D Bode ◽  
Michael F Bode ◽  
Megan Zhao ◽  
Rahul Sakhuja ◽  
Michael A Fifer ◽  
...  

Introduction: The most common complication of alcohol septal ablation (ASA) is periprocedural high grade AV block (HGAVB). No long-term follow-up of cardiovascular implantable electronic device (CIED) utilization after ASA has been reported. Hypothesis: Pacemaker dependence on long-term follow up can be predicted by ECG or procedural characteristics. Methods: We analyzed all patients with hypertrophic cardiomyopathy who underwent ASA from December 1998 to December 2019 at our institution and received their first CIED within 30 days after ASA for HGAVB. All available follow-up interrogations were reviewed. CIED dependence was defined as ventricular pacing of ≥5%. CIED programming was determined by the patients’ cardiologists' discretion. Results: A total of 103 patients with hypertrophic cardiomyopathy underwent ASA. The average follow up duration was 10.1 years. Within 30 days after ASA, a total 25 patients received a CIED for HGAVB. On long term follow-up 16 patients (64%) were found to be CIED-dependent. Baseline characteristics, including pre and post-ASA ECG, were not significantly different between dependent and non-dependent patients (Table). The only predictor for CIED dependence was >1 ml of alcohol injected during ASA (OR 6.0, p<0.046). Conclusions: CIED implantation after ASA is common. Almost two thirds of patients who received CIED for postprocedural HGAVB were CIED-dependent on long term follow up. CIED dependence can be predicted by amount of injected alcohol >1 ml during ASA.


Stroke ◽  
2021 ◽  
Author(s):  
Laurent Fauchier ◽  
Arnaud Bisson ◽  
Alexandre Bodin ◽  
Julien Herbert ◽  
Pascal Spiesser ◽  
...  

Background and Purpose: Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not. Methods: This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHA 2 DS 2 -VASc scores using c-indexes and calibration analysis. Results: In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088–1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177–1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111–1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (all P <0.05). For the HCM Risk-CVA score, CHA 2 DS 2 -VASc score and a French HCM score, all c-indexes were 0.65 to 0.70, with good calibration. Among patients with AF, the CHA 2 DS 2 -VASc score had marginal improvement over the HCM Risk-CVA score but was less predictive compared with the French HCM score ( P =0.001). In patients without AF, both HCM Risk-CVA score and the French HCM score had significantly better prediction compared with CHA 2 DS 2 -VASc (both P <0.0001). Decision curve analysis demonstrated that the French HCM score had the best clinical usefulness of the 3 tested risk scores. Conclusions: Patients with HCM have a high prevalence of AF and a significant risk of IS, and the presence of AF in patients with HCM was independently associated with worse outcomes. A simple French HCM score shows good prediction of IS in patients with HCM and clinical usefulness, with good calibration.


2020 ◽  
Vol 15 (12) ◽  
pp. 1749-1761
Author(s):  
Dorey A. Glenn ◽  
Candace D. Henderson ◽  
Michelle O’Shaughnessy ◽  
Yichun Hu ◽  
Andrew Bomback ◽  
...  

Background and objectivesInfections contribute to patient morbidity and mortality in glomerular disease. We sought to describe the incidence of, and identify risk factors for, infection-related acute care events among Cure Glomerulonephropathy Network (CureGN) study participants.Design, setting, participants, & measurementsCureGN is a prospective, multicenter, cohort study of children and adults with biopsy sample–proven minimal change disease, FSGS, membranous nephropathy, or IgA nephropathy/vasculitis. Risk factors for time to first infection-related acute care events (hospitalization or emergency department visit) were identified using multivariable Cox proportional hazards regression.ResultsOf 1741 participants (43% female, 41% <18 years, 68% White), 163 (9%) experienced infection-related acute care events over a median follow-up of 17 months (interquartile range, 9–26 months). Unadjusted incidence rates of infection-related acute care events were 13.2 and 6.2 events per 100 person-years among pediatric and adult participants, respectively. Among participants with versus without corticosteroid exposure at enrollment, unadjusted incidence rates were 50.6 and 28.6 per 100 person-years, respectively, during the first year of follow-up (adjusted hazard ratio for time to first infection, 1.31; 95% CI, 0.89 to 1.93), and 4.1 and 1.1 per 100 person-years, respectively, after 1 year of follow-up (hazard ratio, 2.99; 95% CI, 1.54 to 5.79). Hypoalbuminemia combined with nephrotic-range proteinuria (serum albumin ≤2.5 g/dl and urinary protein-creatinine ratio >3.5 mg/mg), compared with serum albumin >2.5 g/dl and urinary protein-creatinine ratio ≤3.5 mg/mg, was associated with higher risk of time to first infection (adjusted hazard ratio, 2.49; 95% CI, 1.51 to 4.12).ConclusionsAmong CureGN participants, infection-related acute care events were common and associated with younger age, corticosteroid exposure, and hypoalbuminemia with proteinuria.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Iguchi ◽  
N Masunaga ◽  
M Ishii ◽  
Y An ◽  
M Esato ◽  
...  

Abstract Background Relationship between pulse rate (PR) and cardiac events in patients with sustained (persistent and permanent) atrial fibrillation (AF) in routine clinical practice remains unclear. Methods The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto. Follow-up data were available for 4,454 patients, and we obtained PR at baseline in 2,209 patients of 2,248 sustained AF patients. We divided these patients into four groups based on their PR; G1 (PR≥100 bpm, n=249), G2 (80 bpm≤PR<100 bpm, n=821), G3 (60 bpm≤PR<80 bpm, n=986), and G4 (PR<60 bpm, n=153), and examined the relationship between PR and cardiac events (composite of cardiovascular death and hospitalization for heart failure (HF)). Results Proportion of female and symptomatic AF were more in G1 group, and diastolic blood pressure was higher in G1 group, despite that systolic blood pressure was similar between the four groups. Prevalence of anemia was higher in G1 group, and that of chronic kidney disease was higher in G4 group. Prevalence of HF and left ventricular dysfunction tended to be higher in G1 group but not statistically significant. Beta-blockers and non-dihydropyridine calcium blockers were more often prescribed in G1 group. During the median follow-up of 1,449 days, cardiac events occurred in 399 patients (358 hospitalization for HF and 41 cardiovascular death). In Kaplan-Meier analysis, the incidence of cardiac events were comparable between the four groups (p=0.3). The incidence of all cause death (p=0.06) and stroke or systemic embolism (p=0.4) was also similar between the four groups. The incidence of cardiac events did not differ between the four groups when we divided the patients based on the presence of HF at baseline, and the incidence of cardiac events was also comparable between the four groups after adjusting potential confounders. However, when we examined the impact of PR according to 10 bpm increment, patients with very low PR (<50 bpm) (hazard ratio [95% confidence intervals], 2.22 [1.04–4.15]) and very high PR (≥110 bpm) (hazard ratio [95% confidence intervals], 1.67 [1.00–2.64]) had higher incidence of cardiac events than patients with PR of 70–79 bpm (Figure). Furthermore, we acquired the annual follow-up data of PR. Mean PR during the follow-up periods was not different between patients with cardiac events and those without (with vs without, 79.5±15.3 bpm vs 79.7±12.7 bpm; p=0.8), whereas maximum PR was less in patients with cardiac events (85.2±17.5 bpm vs 89.3±16.2 bpm; p<0.0001). Patients with maximum PR<60 bpm showed higher incidence of cardiac events, and the incidence of cardiac events was the lowest in patients with maximum PR of 80 to 99 bpm (maximum PR<60 bpm: 31.3%, 60–79 bpm: 24.5%, 80–99 bpm: 14.5%, 100 bpm: 16.1%; P<ehz746.03881). Conclusion PR did not appear to have strong impact on cardiac events in patients with sustained AF. However, low PR might be a risk for developing cardiac events. Acknowledgement/Funding Japan Agency for Medical Research and Development, AMED (15656344, 16768811), Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb


2013 ◽  
Vol 35 ◽  
pp. 857-862 ◽  
Author(s):  
Anping Cai ◽  
Liwen Li ◽  
Ying Zhang ◽  
Yujin Mo ◽  
Zhigen Li ◽  
...  

Background and Aim. Incidence of coronary restenosis after stent placement is high. Our study was going to investigate whether Lp(a) elevation was potential for predicting coronary restenosis and whether the effects of Lp(a) elevation on coronary restenosis were dependent on LDL-C level.Methods and Results. Totally 832 participants eligible for stent placement were enrolled and followed up for monitoring clinical end points. Baseline characteristics were collected. According to the cut point of Lp(a), participants were divided into low Lp(a) group (Lp(a) < 30 mg/dL) and high Lp(a) group (Lp(a) ≥ 30 mg/dL). Furthermore, based on baseline LDL-C level, participants were divided into LDL-C < 1.8 mmol/L and ≥1.8 mmol/L subgroups. Clinical end points including major adverse cardiovascular events (MACE), cardiovascular death, nonfatal myocardial infarction, ischemic stroke, and coronary revascularization (CR) were compared. Patients in high Lp(a) groups more frequently presented with acute coronary syndrome and three vessel stenoses. In subgroup of LDL-C < 1.8 mmol/L, no significant differences of cardiovascular outcomes were found between low and high Lp(a) groups. While in the subgroup of LDL-C ≥ 1.8 mmol/L, incidences of MACE and CR were significantly higher in high Lp(a) group, and odds ratio for CR was 2.05.Conclusion. With baseline LDL-C and Lp(a) elevations, incidence of CR is significantly increased after stent placement.


2014 ◽  
Vol 99 (5) ◽  
pp. 1599-1607 ◽  
Author(s):  
Tzu-Chieh Lin ◽  
Cheng-Han Lee ◽  
Chyun-Yu Yang ◽  
Yea-Huei Kao Yang ◽  
Swu-Jane Lin

Context: There was no clear evidence for the association between oral bisphosphonates or raloxifene and venous thromboembolism (VTE). There might also be ethnic differences in VTE risk. Objective: The purpose of this study was to compare the incidence and risk of VTEs for different classes of osteoporosis drugs in the Taiwanese osteoporotic fracture population. Design: This was a retrospective cohort study from 2003 to 2007, with up to 6 years follow-up. Setting: Enrollees were participants in Taiwan National Health Insurance. Patients: Patients older than 50 years who had vertebral or hip fractures and were new to osteoporosis therapy were recruited. Intervention: Patients were classified into the alendronate, calcitonin, or raloxifene group according to exposure after follow-up. Main Outcome Measure: The primary outcome of our study was all incident VTEs, including deep vein thrombosis and pulmonary embolism. Cox proportional hazard models were used to compare the relative VTE risk among alendronate, raloxifene, and calcitonin groups under an on-treatment scenario. Results: There were 25 443, 9642, and 31 900 patients in the alendronate, raloxifene, and calcitonin groups, and the mean age was 74.5 years (SD, 9.6). The incidence of VTE in the alendronate, raloxifene, and calcitonin groups was 11.2, 8.5, and 18.8 per 10 000 person-years. Results from Cox analyses showed that alendronate or raloxifene recipients did not have a higher risk for VTE than calcitonin recipients (adjusted hazard ratio for alendronate, 0.84; 95% confidence interval, 0.47–1.51; adjusted hazard ratio for raloxifene, 0.64; 95% confidence interval, 0.33–1.28). Conclusion: This retrospective analysis found that the incidence of VTE in Taiwanese patients with osteoporosis was low, and the risk of VTE was similar across alendronate, raloxifene, and calcitonin recipients in patients with osteoporotic fractures who were new to osteoporosis therapy.


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