Purpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in... Show morePurpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.Methods: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.Results: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p < 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p < 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor) epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.Conclusion: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis. Show less
Delgado, V.; Marsan, N.; Waha, S. de; Bonaros, N.; Brida, M.; Burri, H.; ... ; ESC Sci Document Grp 2023
PurposeHeavy pigmentation is known to be a prognostic risk factor in uveal melanoma (UM). We analyzed whether genetic tumor parameters were associated with tumor pigmentation and whether... Show morePurposeHeavy pigmentation is known to be a prognostic risk factor in uveal melanoma (UM). We analyzed whether genetic tumor parameters were associated with tumor pigmentation and whether pigmentation should be included in prognostic tests.DesignRetrospective comparison of clinical, histopathological, and genetic features and survival in UM with different pigmentation.ParticipantsA total of 1058 patients with UM from a White European population with diverse eye colors enucleated between 1972 and 2021.MethodsCox regression and log-rank tests were used for survival analysis; the chi-square test and Mann–Whitney U test were used for correlation analysis.Main Outcome MeasuresUveal melanoma–related survival based on tumor pigmentation and chromosome status, correlation of tumor pigmentation with prognostic factors.ResultsThe 5-year UM-related mortality was 8% in patients with nonpigmented tumors (n = 54), 25% with lightly pigmented tumors (n = 489), 41% with moderately pigmented tumors (n = 333), and 33% with dark tumors (n = 178) (P < 0.001). The percentage of tumors with monosomy 3 (M3) or 8q gain increased with increasing pigmentation (31%, 46%, 62%, and 70% having M3 [P < 0.001], and 19%, 43%, 61%, and 63% having 8q gain [P < 0.001] in the 4 increasing pigment groups, respectively). BRCA-associated protein 1(BAP1) loss (known for 204 cases) was associated with increased tumor pigmentation (P = 0.001). Cox regression analysis on survival showed that when chromosome status and pigmentation were both included, pigmentation was not an independent prognostic indicator. Preferentially expressed antigen in melanoma (PRAME) expression was a significant prognostic marker in light tumors (P = 0.02) but not in dark tumors (P = 0.85).ConclusionsPatients with moderately and heavily pigmented tumors showed a significantly higher UM-related mortality than patients with unpigmented and light tumors (P < 0.001), supporting prior reports on the relation between increased tumor pigmentation and a worse prognosis. Although we previously showed that a dark eye color was associated with tumor pigmentation, we now show that the tumor’s genetic status (chromosome 3 and 8q/BAP1 status) is also related to tumor pigmentation. When pigmentation and chromosome 3 status are both included in a Cox regression analysis, pigmentation is not an independent prognostic factor. However, evidence from this and previous studies shows that chromosome changes and PRAME expression have a stronger association with survival when they occur in light tumors than in dark ones. Show less
Galloo, X.; Meucci, M.C.; Stassen, J.; Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; ... ; Delgado, V. 2023
Background: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study... Show moreBackground: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study evaluated RV reverse remodeling, based on changes in RV dimensions and function, after TV surgery for significant (moderate or severe) tricuspid regurgitation (TR) and their association with outcome. Methods: A total of 121 patients (mean age 63 +/- 12 years, 47% males) with significant TR treated with TV surgery were included in this analysis. The population was stratified by tertiles of percentage reduction of RV end-systolic area (RVESA) and absolute change of RV fractional area change (RVFAC). Five-year mortality rates were compared across the tertiles of RV remodeling and independent associates of mortality were investigated. Results: Tertile 3 consisted of patients presenting with a reduction in RVESA >= 17.2% and an improvement in RVFAC >= 2.3% after TV surgery. Cumulative survival rates were significantly better in patients within tertile 3 of RVESA reduction: 90% vs. 49% for tertile 1 and 69% for tertile 2 (log-rank p = 0.002) and within tertile 3 of RVFAC improvement: 87% vs. 57% for tertile 1 and 65% for tertile 2 (log-rank p = 0.02). Tertiles 3 of RVESA reduction and RVFAC improvement were both independently associated with better survival after TV surgery compared to tertiles 1 (hazard ratio: 0.221 [95% CI: 0.074-0.658] and 0.327 [95% CI: 0.118-0.907], respectively). Conclusions: The extent of RV reverse remodeling, based on reduction in RVESA and improvement in RVFAC, was associated with better survival at 5-year follow-up of TV surgery for significant TR. Show less
Background: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under... Show moreBackground: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. Aims: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Ad-olescents Young Adults (AYAs; aged 18-39) and older adults. Methods: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cu-mulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. Results: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients >= 18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95% CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). Conclusions: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types. Show less
Introduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms... Show moreIntroduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. Materials and methods: Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. Results: After exclusion of 176 patients, 10113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. Conclusion: The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic... Show moreBackground: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2). Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance. Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0. 902 for patients with ER-positive tumours (p = 2.3 x 10(-6)) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted. Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predic-tions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration. (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Quaas, A.; Biesma, H.D.; Wagner, A.D.; Verheij, M.; Henegouwen, M.I.V.; Schoemig-Markiefka, B.; ... ; Grieken, N.C.T. van 2022
Objective: Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability ... Show moreObjective: Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). Design: We analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio) therapy. Results: MSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p < 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC ( HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). Conclusions: MSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. Show less
Yedidya, I.; Butcher, S.C.; Stassen, J.; Bijl, P. van der; Ngiam, J.N.; Chew, N.W.S.; ... ; Bax, J.J. 2022
Purpose Degenerative mitral stenosis (DMS) is associated with a poor prognosis. Although mean transmitral gradient (TMG) has shown a good correlation with outcome, little is known about the... Show morePurpose Degenerative mitral stenosis (DMS) is associated with a poor prognosis. Although mean transmitral gradient (TMG) has shown a good correlation with outcome, little is known about the association between other echocardiographic parameters and prognosis in patients with DMS. The current study aimed to evaluate the prognostic value of left atrial volume index (LAVI) in patients with DMS. Methods A total of 155 patients with DMS (72[63-80] years, 67% female) were included. The population was divided according to LAVI: normal-sized LAVI (LAVI <= 34 ml/m2); and enlarged LAVI (> 34 ml/m2). Results Patients with enlarged LAVI had a higher left ventricular mass index (120[96-146] vs. 91[70-112] g/m2 p < 0.001), as well as a higher prevalence of significant mitral regurgitation and severe aortic stenosis (23% vs. 10% p = 0.046 and 38% vs. 15% p=0.001, respectively) compared to patients with normal-sized LAVI. During a median follow-up of 25 months, 56 (36%) patients died. Patients with enlarged LAVI had worse prognosis compared to patients with normal-sized LAVI (p = 0.026). In multivariable Cox regression model, an enlarged LAVI was independently associated with all-cause mortality (HR 2.009, 95% CI 1.040 to 3.880, P = 0.038). Conclusion An enlarged LAVI (> 34 ml/m2) is significantly associated with excess mortality in patients with DMS. After adjusting for potential confounders, an enlarged LAVI was the only parameter that remained independently associated with prognosis. Show less
Aims Pulmonary arterial hypertension (PAH) is a rare but serious disease associated with high mortality if left untreated. This study aims to assess the prognostic cardiac magnetic resonance (CMR)... Show moreAims Pulmonary arterial hypertension (PAH) is a rare but serious disease associated with high mortality if left untreated. This study aims to assess the prognostic cardiac magnetic resonance (CMR) features in PAH using machine learning. Methods and results Seven hundred and twenty-three consecutive treatment-naive PAH patients were identified from the ASPIRE registry; 516 were included in the training, and 207 in the validation cohort. A multilinear principal component analysis (MPCA)-based machine learning approach was used to extract mortality and survival features throughout the cardiac cycle. The features were overlaid on the original imaging using thresholding and clustering of high- and low-risk of mortality prediction values. The 1-year mortality rate in the validation cohort was 10%. Univariable Cox regression analysis of the combined short-axis and four-chamber MPCA-based predictions was statistically significant (hazard ratios: 2.1, 95% CI: 1.3, 3.4, c-index = 0.70, P = 0.002). The MPCA features improved the 1-year mortality prediction of REVEAL from c-index = 0.71 to 0.76 (P ≤ 0.001). Abnormalities in the end-systolic interventricular septum and end-diastolic left ventricle indicated the highest risk of mortality.Conclusion: The MPCA-based machine learning is an explainable time-resolved approach that allows visualization of prognostic cardiac features throughout the cardiac cycle at the population level, making this approach transparent and clinically interpretable. In addition, the added prognostic value over the REVEAL risk score and CMR volumetric measurements allows for a more accurate prediction of 1-year mortality risk in PAH. Show less
OBJECTIVES: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery.METHODS:... Show moreOBJECTIVES: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery.METHODS: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest.RESULTS: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively).CONCLUSIONS: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure. Show less
Purpose: Individuals with gray, blue, or green eyes have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might be related not... Show morePurpose: Individuals with gray, blue, or green eyes have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might be related not only to predisposition to UM but also to its behavior; therefore, we compared the clinical, histopathologic, and genetic characteristics of UM between eyes with different colors. Design: We determined iris color in a large cohort of patients enucleated for UM. Clinical and histopathologic tumor characteristics, chromosome status, and survival were compared among 3 groups on the basis of iris color. Participants: A total of 412 patients with choroidal/ciliary body UM, who had undergone primary enucleation at the Leiden University Medical Center, Leiden, The Netherlands, between 1993 and 2019, were divided into 3 groups based on iris color: gray/blue, green/hazel, and brown. The validation cohort included 934 patients with choroidal/ciliary body UM treated at Wills Eye Hospital (WEH). Methods: Comparison of clinical, histopathologic, and genetic characteristics of UM in patients with different iris colors. Main Outcome Measures: Melanoma-related survival in UM patients, divided over 3 iris color groups, in relation to the tumor's chromosome 3 and 8q status. Results: Moderate and heavy tumor pigmentations were especially seen in eyes with a brown iris (P < 0.001). Survival did not differ between patients with different iris colors (P = 0.27); however, in patients with a light iris, copy number changes in chromosome 3 and 8q had a greater influence on survival than in patients with a dark iris. Likewise, chromosome 3 and chromosome 8q status affected survival more among patients with lightly pigmented tumors than in patients with heavily pigmented tumors. The WEH cohort similarly showed a greater influence of chromosome aberrations in light-eyed individuals. Conclusions: Although iris color by itself did not relate to UM-related survival, chromosome 3 and 8q aberrations had a larger influence on survival in patients with a light iris than those with a brown iris. This suggests a synergistic effect of iris pigmentation and chromosome status in the regulation of oncogenic behavior of UM. Iris color should be taken into consideration when calculating a patient's risk for developing metastases. (C) 2021 by the American Academy of Ophthalmology. Show less
Purpose: Uveal melanoma (UM) is a rare disease and the most common primary intraocular malignancy in adults, with a high risk of metastases. Reliable prognostication systems are based on anatomic... Show morePurpose: Uveal melanoma (UM) is a rare disease and the most common primary intraocular malignancy in adults, with a high risk of metastases. Reliable prognostication systems are based on anatomic features, as in the tumor-node-metastasis staging of the American Joint Committee on Cancer (AJCC) system, or on genetic information, as in The Cancer Genome Atlas (TCGA) system. Prior evidence suggests that combining both systems may be beneficial. We evaluated the benefit of combining the TCGA and AJCC systems in a large cohort of patients.Design: Retrospective case series of patients with UM.Participants: Nine hundred seventy-nine patients with a choroidal or ciliary body melanoma treated at the Wills Eye Hospital between 1998 and 2020, 94% of whom received eye-sparing treatment.Methods: Tumors were classified into 4 TCGA groups based on chromosome copy number: A (disomy 3, normal 8q), B (disomy 3, any 8q gain), C (monosomy 3, 1 extra copy of 8q), and D (monosomy 3, multiple 8q gain). The eighth edition of the AJCC staging manual was used for AJCC staging. Cox regression and the log-rank test were used for survival analysis.Main Outcome Measure: Metastasis-free survival.Results: Combining information of the 2 systems improved prognostication in intermediate groups: in TCGA group C, we saw an increased rate of metastasis in AJCC stage III (28%) compared with stage 11 (8.9%); the same was seen in AJCC stage II, going from TCGA group C (8.9%) to group D (46%), and in AJCC stage III, going from group C (28%) to group D (49%). In patients with AJCC stage II or III disease, loss of chromosome 3 and gain of 8q (TCGA groups C and D) significantly worsened the prognosis, with multiple 8q gain (TCGA group D) having a greater impact.Conclusions: Combining information from AJCC stages and TCGA groups yields a better predictive power even in this set of relatively small tumors. We propose that physicians take both systems into account whenever possible, especially in moderate-risk groups. (C) 2021 by the American Academy of Ophthalmology. Show less
Stassen, J.; Galloo, X.; Hirasawa, K.; Marsan, N.A.; Bijl, P. van der; Delgado, V.; Bax, J.J. 2022
Aims Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT)... Show moreAims Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome. Methods and results Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 +/- 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424). Conclusion Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality. Show less
Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation... Show moreAims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC. Methods and results: We classified 617 definite ARVC patients (38.5 +/- 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA. Conclusion: The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC. Show less
Background: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective... Show moreBackground: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity.Method: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes.Results: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered.Limitations: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant.Conclusions: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of sub-threshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research. Show less
Introduction It is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis,... Show moreIntroduction It is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis, stage, and treatment. We aimed to assess long-term survival trends after STEMI in this population to evaluate both cardiovascular and cancer-related drivers of prognosis over a follow-up period of 5 years. Methods In this retrospective single-center cohort study, patients with a prior cancer diagnosis admitted with STEMI between 2004 and 2014 and treated with primary percutaneous coronary intervention (PCI) were recruited from the STEMI clinical registry of our institution. Results In the 211 included patients, the cumulative incidence of all-cause death after 5 years of follow-up was 38.1% (N = 60). The cause of death was predominantly malignancy-related (N = 29, 48.3% of deaths) and nine patients (15.0%) died of a cardiovascular cause. After correcting for age and sex, a recent cancer diagnosis (< 1 year relative to > 10 years, HRadj 2.98 [95% CI: 1.39-6.41], p = 0.005) and distant metastasis at presentation (HRadj 4.02 [1.70-9.53], p = 0.002) were significant predictors of long-term mortality. While maximum levels of cardiac troponin-T and creatinine kinase showed significant association with mortality (resp. HRadj 1.34 [1.08-1.66], p = 0.008; HRadj 1.36 [1.05-1.76], p = 0.019), other known determinants of prognosis after STEMI, e.g., hypertension and renal insufficiency, were not significantly associated with survival. Conclusions Patients with a prior cancer diagnosis admitted with STEMI have a poor survival rate. However, when the STEMI is optimally treated with primary PCI and medication, cardiac mortality is low, and prognosis is mainly determined by factors related to cancer stage. Show less
Objective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at... Show moreObjective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation. Study Design and Setting: We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation (n = 556) and assessed the change in discrimination (dAUC) in external validation cohorts (n = 1,147). Results: PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 527 of 556 CPMs (95%) were classified as high ROB, 20 (3.6%) low ROB, and 9 (1.6%) unclear ROB. Only one model with unclear ROB was reclassified to high ROB after full PROBAST assessment of all low and unclear ROB models. Median change in discrimination was significantly smaller in low ROB models (dAUC -0.9%, IQR -6.2-4.2%) compared to high ROB models (dAUC -11.7%, IQR -33.3-2.6%; P < 0.001). Conclusion: High ROB is pervasive among published CPMs. It is associated with poor discriminative performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http:// creativecommons.org/ licenses/ by- nc- nd/ 4.0/ ) Show less
Fortuni, F.; Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; Ferrari, G.M. de; Bax, J.J.; ... ; Marsan, N.A. 2021
Background: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can... Show moreBackground: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can be proportional or disproportional to the dilation of the tricuspid annulus (TA) and investigated the prognostic impact of this novel definition. Methods: A total of 334 patients with moderate to severe STR and preserved left ventricular systolic function were included. The ratio between vena contracta (VC) width and tricuspid annular diameter was calculated. The cutoff value for VC/TA ratio associated with increased risk for all-cause death was identified using spline-curve analysis. Results: The cutoff value of VC/TA ratio associated with a mortality excess was 0.24, and 165 patients (49%) had VC/TA ratios >_ 0.24. Compared with those with VC/TA ratios < 0.24, patients with VC/TA ratios >_ 0.24 had a higher prevalence of moderate to severe mitral regurgitation, had higher pulmonary pressures, and were more frequently treated with diuretics. During a median follow-up period of 62 months (interquartile range, 28-101 months), 128 patients (38%) died. The cumulative 5-year survival rate was significantly worse in patients with VC/TA ratios >_ 0.24 (55% vs 71%, P = .001). VC/TA ratio >_ 0.24 was independently associated with poor outcomes on multivariate analysis (hazard ratio, 1.567; 95% CI, 1.044-2.352; P = .030) together with coronary artery disease, renal impairment, right ventricular systolic function (evaluated using either tricuspid annular plane systolic excursion or right ventricular free wall strain), and pulmonary pressures. Conclusions: VC/TA ratio >_ 0.24 is independently associated with poor prognosis in patients with STR. This parameter may be considered as a marker of disproportionate STR and could improve risk stratification and clinical decision-making. (J Am Soc Echocardiogr 2021;34:944-54.) Show less
Namazi, F.; Bijl, P. van der; Vo, N.M.; Wijngaarden, S.E. van; Marsan, N.A.; Delgado, V.; Bax, J.J. 2021
Aims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of... Show moreAims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes.Methods Patients with significant secondary MR, of both ischaemic and non-ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all-cause mortality.Results A total of 698 patients (mean age 66 +/- 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non-ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 +/- 4.1% vs. 7.5 +/- 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow-up of 57 [interquartile range 29-110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1-, 2- and 5-year follow-up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001).Conclusions Significant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis. Show less
