The association of artificial intelligence-enabled electrocardiogram-derived age (physiologic age) with atherosclerotic cardiovascular events in the community

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Medina-Inojosa ◽  
A Ladejobi ◽  
Z Attia ◽  
M Shelly-Cohen ◽  
B Gersh ◽  
...  

Abstract Background We have demonstrated that artificial intelligence interpretation of ECGs (AI-ECG) can estimate an individual's physiologic age and that the gap between AI-ECG and chronologic age (Age-Gap) is associated with increased mortality. We hypothesized that Age-Gap would predict long-term atherosclerotic cardiovascular disease (ASCVD) and that Age-Gap would refine the ACC/AHA Pooled Cohort Equations' (PCE) predictive abilities. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients seeking primary care between 1998–2000 and followed through March 2016. Inclusion criteria were age 40–79 and complete data to calculate PCE. We excluded those with known ASCVD, AF, HF or an event within 30 days of baseline.A neural network, trained, validated, and tested in an independent cohort of ∼ 500,000 independent patients, using 10-second digital samples of raw, 12 lead ECGs. PCE was categorized as low<5%, intermediate 5–9.9%, high 10–19.9%, and very high≥20%. The primary endpoint was ASCVD and included fatal and non-fatal myocardial infarction and ischemic stroke; the secondary endpoint also included coronary revascularization [Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG)], TIA and Cardiovascular mortality. Events were validated in duplicate. Follow-up was truncated at 10 years for PCE analysis. The association between Age-Gap with ASCVD and expanded ASCVD was assessed with cox proportional hazard models that adjusted for chronological age, sex and risk factors. Models were stratified by PCE risk categories to evaluate the effect of PCE predicted risk. Results We included 24,793 patients (54% women, 95% Caucasian) with mean follow up of 12.6±5.1 years. 2,366 (9.5%) developed ASCVD events and 3,401 (13.7%) the expanded ASCVD. Mean chronologic age was 53.6±11.6 years and the AI-ECG age was 54.5±10.9 years, R2=0.7865, p<0.0001. The mean Age-Gap was 0.87±7.38 years. After adjusting for age and sex, those considered older by ECG, compared to their chronologic age had a higher risk for ASCVD when compared to those with <−2 SD age gap (considered younger by ECG). (Figure 1A), with similar results when using the expanded definition of ASCVD (data not shown). Furthermore, Age-Gap enhanced predicted capabilities of the PCE among those with low 10-year predicted risk (<5%): Age and sex adjusted HR 4.73, 95% CI 1.42–15.74, p-value=0.01 and among those with high predicted risk (>20%) age and sex adjusted HR 6.90, 95% CI 1.98–24.08, p-value=0.0006, when comparing those older to younger by ECG respectively (Figure 1B). Conclusion The difference between physiologic AI-ECG age and chronologic age is associated with long-term ASCVD, and enhances current risk calculators (PCE) ability to identify high and low risk individuals. This may help identify individuals who should or should not be treated with newer, expensive risk-reducing therapies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Medina-Inojosa ◽  
V.K Somers ◽  
S Hayes ◽  
R Mankad ◽  
F Lopez-Jimenez

Abstract Background The ACC/AHA Pooled Cohort Equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) has been recommended as the initial step in cardiovascular risk assessment. The sensitivity of this tool to detect those who will develop ASCVD within 10-years, while considering age and sex groups, has not been extensively studied. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients that sought primary care in Olmsted County, MN, between the years 1998–2000 and were followed up through March 1st 2016. Inclusion criteria were ages 40–79 and complete data to calculate the PCE. We excluded those with known ASCVD, atrial fibrillation or heart failure. Criteria were similar to those used to derive the PCE. Events were validated in duplicate and included fatal and non-fatal myocardial infarction and ischemic stroke. Patient information was ascertained using the record linkage system of the REP. Follow-up was truncated at 10 years. We assessed the ASCVD predicted risk (categorized as low <5%, intermediate 5–9.9%, high 10–19.9%, and very high ≥20% risk) at baseline, in subjects having an ASCVD event within 10-years in the community across age (<65 years) and sex categories. We also categorized ideal cardiovascular health as ≥4 metrics [non-smoker, body mass index <25 kg/m2, and not having of elevated blood pressure (≥130/80 mmHg), LDL cholesterol (>100 mg/dL), or fasting blood glucose (>100 mg/dL), in the absence of a medical diagnosis or treatment]. Results We included 30,042 adults, mean ± SD age 48.5±12.2 years, 54% women, with a median follow-up of 16.5±5.3 years. There were 1,555 ASCVD events (5.2%) at 10 years of follow-up. The performance of the PCE was similar to what was described in the original report (0.78 vs 0.79). Overall, among those who suffered an ASCVD, 54% of women and 41% of men were not high risk as predicted by PCE (Figure 1A). Most women (73%) <65 years of age would had been considered low risk within 10-years before the event, and only 10% would have been considered to be high risks (Figure 1B). Nonetheless, women <65 years who had an ASCVD event and low 10-year predicted ASCVD risk by PCE were less likely to have ideal cardiovascular health [55 (0.40%) vs 3884 (28.39%), p-value<0.0001], when compared to women in the low risk category without an event. Conclusion The PCE fails to identify most women who will develop an ASCVD event, particularly women <65 years of age. These results underscore the importance of using additional information when estimating ASCVD risk among women and the need for better cardiovascular risk prediction tools. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Katbeh ◽  
T De Potter ◽  
P Geelen ◽  
E Stefanidis ◽  
K Iliodromitis ◽  
...  

Abstract Background Atrial structural and functional changes may develop as a result of catheter ablation (CA) in patients with paroxysmal and persistent atrial fibrillation (AF). However, the relation between AF recurrence and atrial performance following CA is still under debate. Our aim is to describe the long-term effects of CA on LA remodeling and its correlates to the maintenance of sinus rhythm (SR). Methods We prospectively enrolled 178 consecutive patients (age: 63±9 years, 35% females) with paroxysmal AF undergoing first-CA (67%) or redo-CA (22%), and 20 individuals (11%) with long-standing persistent AF (PAF) undergoing first CA. All patients underwent comprehensive transthoracic echocardiography at baseline and at 12-month follow-up, including the assessment of reservoir and contractile strain (LAS) using two dimensional speckle tracking echocardiography in all three apical views. The study population was divided in two sub-groups according to AF recurrence during follow-up. Results During one-year follow-up, 144 (81%) patients maintained SR whereas 34 (19%) patients had AF recurrence [first-CA group 16 (13%), redo-CA group 8 (20%) and PAF group 10 (50%)]. Improvement of LAS was observed only in patients with paroxysmal and long-standing persistent AF who underwent the first CA and who remained in SR (Figure 1A, 1C). In contrast, recurrent AF was associated with absence of LAS improvement (Figure 1A, 1C). Different time course of LA performance was observed in the redo-CA group, i.e. LAS remained unchanged from baseline regardless of long-term maintenance of SR (Figure 1B). Moreover, at follow-up, no significant differences in LAS between redo-CA patients with SR versus AF were observed. Of note, in patients with long-standing persistent AF and SR, follow-up LAS increased to values observed in the redo-CA group. Conclusion LA performance following CA is strongly affected by complex interplay between extent of atrial electro-structural remodeling and CA procedure. Repeated wide CA might affects negatively LA compliance and contractility despite SR restoration. Figure 1. Reservoir and contractile LAS at Baseline and 12-month follow-up in the First-CA (1A), the Redo-CA (1B) and the long-standing persistent AF (1C) groups in patients who maintained SR versus patients who had AF recurrence. *p value <0.05 (baseline vs. follow-up). Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Huang ◽  
C Liu

Abstract Background Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear. Purpose To examine the association of long-term SBP and all-cause mortality among patients with HFpEF. Methods We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: <120mmHg, ≥120mmHg and <130mmHg, ≥130mmHg and <140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%. Results The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of <120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of <120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis. Conclusions Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.L Xu ◽  
J Luo ◽  
H.Q Li ◽  
Z.Q Li ◽  
B.X Liu ◽  
...  

Abstract Background New-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on subsequent heart failure (HF) is still not well studied. We aimed to investigate the relationship between NOAF following AMI and HF hospitalization. Methods This retrospective cohort study was conducted between February 2014 and March 2018, using data from the New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai registry, where all participants did not have a documented AF history. Patients with AMI who discharged alive and had complete echocardiography and follow-up data were analyzed. The primary outcome was HF hospitalization, which was defined as a minimum of an overnight hospital stay of a participant who presented with symptoms and signs of HF or received intravenous diuretics. Results A total of 2075 patients were included, of whom 228 developed NOAF during the index AMI hospitalization. During up to 5 years of follow-up (median: 2.7 years), 205 patients (9.9%) experienced HF hospitalization and 220 patients (10.6%) died. The incidence rate of HF hospitalization among patients with NOAF was 18.4% per year compared with 2.8% per year for those with sinus rhythm. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (hazard ratio [HR]: 3.14, 95% confidence interval [CI]: 2.30–4.28; p<0.001). Consistent result was observed after accounting for the competing risk of all-cause death (subdistribution HR: 3.06, 95% CI: 2.18–4.30; p<0.001) or performing a propensity score adjusted multivariable model (HR: 3.28, 95% CI: 2.39–4.50; p<0.001). Furthermore, the risk of HF hospitalization was significantly higher in patients with persistent NOAF (HR: 5.81; 95% CI: 3.59–9.41) compared with that in those with transient NOAF (HR: 2.61; 95% CI: 1.84–3.70; p interaction = 0.008). Conclusion NOAF complicating AMI is strongly associated with an increased long-term risk of heart. Cumulative incidence of outcome Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. National Natural Science Foundation of China, 2. Natural Science Foundation of Shanghai


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Wienbergen ◽  
A Fach ◽  
S Meyer ◽  
J Schmucker ◽  
R Osteresch ◽  
...  

Abstract Background The effects of an intensive prevention program (IPP) for 12 months following 3-week rehabilitation after myocardial infarction (MI) have been proven by the randomized IPP trial. The present study investigates if the effects of IPP persist one year after termination of the program and if a reintervention after >24 months (“prevention boost”) is effective. Methods In the IPP trial patients were recruited during hospitalization for acute MI and randomly assigned to IPP versus usual care (UC) one month after discharge (after 3-week rehabilitation). IPP was coordinated by non-physician prevention assistants and included intensive group education sessions, telephone calls, telemetric and clinical control of risk factors. Primary study endpoint was the IPP Prevention Score, a sum score evaluating six major risk factors. The score ranges from 0 to 15 points, with a score of 15 points indicating best risk factor control. In the present study the effects of IPP were investigated after 24 months – one year after termination of the program. Thereafter, patients of the IPP study arm with at least one insufficiently controlled risk factor were randomly assigned to a 2-months reintervention (“prevention boost”) vs. no reintervention. Results At long-term follow-up after 24 months, 129 patients of the IPP study arm were compared to 136 patients of the UC study arm. IPP was associated with a significantly better risk factor control compared to UC at 24 months (IPP Prevention Score 10.9±2.3 points in the IPP group vs. 9.4±2.3 points in the UC group, p<0.01). However, in the IPP group a decrease of risk factor control was observed at the 24-months visit compared to the 12-months visit at the end of the prevention program (IPP Prevention Score 10.9±2.3 points at 24 months vs. 11.6±2.2 points at 12 months, p<0.05, Figure 1). A 2-months reintervention (“prevention boost”) was effective to improve risk factor control during long-term course: IPP Prevention Score increased from 10.5±2.1 points to 10.7±1.9 points in the reintervention group, while it decreased from 10.5±2.1 points to 9.7±2.1 points in the group without reintervention (p<0.05 between the groups, Figure 1). Conclusions IPP was associated with a better risk factor control compared to UC during 24 months; however, a deterioration of risk factors after termination of IPP suggests that even a 12-months prevention program is not long enough. The effects of a short reintervention after >24 months (“prevention boost”) indicate the need for prevention concepts that are based on repetitive personal contacts during long-term course after coronary events. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Stiftung Bremer Herzen (Bremen Heart Foundation)


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1048.2-1048
Author(s):  
S. Herrera ◽  
J. C. Diaz-Coronado ◽  
D. Rojas-Gualdrón ◽  
L. Betancur-Vasquez ◽  
D. Gonzalez-Hurtado ◽  
...  

Background:Systemic lupus erythematosus (SLE) clinical manifestations, and their severity, vary according to age, ethnicity and socioeconomic status. Both Hispanic and Afro-Americans have a higher incidence and more sever presentation when compared to Caucasian patients with SLEObjectives:To analyze clinical and immunological characteristics associated with time to severe renal involvement in patients with Systemic Lupus Erythematous in a Colombian cohort followed for one year, between January 2015 and December 2018Methods:Retrospective follow-up study based in clinical records. Patients with SLE diagnosis that fulfilled either 1987 American College of Rheumatology Classification Criteria for SLE or 2011 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. We included patients with diagnosis of lupus nephritis according to Wallace and Dubois criteria. Patients who did not have at least two follow-up measurements or had a cause of nephritis other than lupus were excluded. The main outcome was defined as time from diagnosis to sever renal involvement defined as creatinine clearance ≤50 ml/min, 24-hour proteinuria ≥3.5 grams o end stage renal disease.We analyzed clinical and immunological characteristics. Descriptive statistical analyses of participant data during the first evaluation are reported as frequencies and percentages for categorical variables, and as medians and interquartile ranges (IQR) for quantitative variables. Age and sex adjusted survival functions and Hazard ratios (HR) with 95% confidence intervals and p-values were estimated using parametric Weibull models por interval-censored data. P values < 0.05 were considered statistically significantResults:548 patients were analyzed: 67 were left-censored as they presented renal involvement at entry, 6 were interval censored as outcome occurred between study visits, and 475 were right-censored as involvement was not registered during follow-up. 529 (96.5%) patients were female, median age at entry was 46 (IQR = 23) and median age to diagnosis was 29.5 (IQR = 20.6). 67% were mestizo, 13% Caucasian and 0.3% Afro-Colombian. Age and sex adjusted variables associated with time to severe lupus nephritis were high blood pressure HR = 3.5 (95%CI 2.2-5.6; p-value <0.001) and Anti-RO (per unit increase) HR = 1.002 (95%CI 1.001-1.004; p-value = 0.04). Figure 1 shows age and sex adjusted survival function.Conclusion:In our cohort the appearance of severe lupus nephritis occurs in less than 15% of patients at 10 years. Both high blood pressure and elevated anti-Ro titers were associated with a higher rate of onset in the presentation of severe lupus nephritis, as seen in some polymorphs of anti Ro.References:Disclosure of Interests:Sebastian Herrera Speakers bureau: academic conference, Juan camilo Diaz-Coronado: None declared, Diego Rojas-Gualdrón: None declared, Laura Betancur-Vasquez: None declared, Daniel Gonzalez-Hurtado: None declared, Juanita Gonzalez-Arango: None declared, laura Uribe-Arango: None declared, Maria Fernanda Saavedra Chacón: None declared, Jorge Lacouture-Fierro: None declared, Santiago Monsalve: None declared, Sebastian Guerra-Zarama: None declared, Juan david Lopez: None declared, Juan david Serna: None declared, Julian Barbosa: None declared, Ana Sierra: None declared, Deicy Hernandez-Parra: None declared, Ricardo Pineda.Tamayo: None declared


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (&lt;2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score &gt;2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.


1984 ◽  
Vol 5 (8) ◽  
pp. 248-254
Author(s):  
Leonard G. Feld ◽  
Morris J. Schoeneman ◽  
Frederick J. Kaskel

Asymptomatic proteinuria is defined as the discovery of proteinuria on a routine examination without evidence of clinical disease. The prevalence is dependent on the age and sex of the child, as well as the circumstances under which the testing is performed. In the majority of cases, patients have transient or orthostatic proteinuria. The physician can assure the patient and parents that the prognosis is excellent. However, appropriate long-term follow-up is essential. On the other hand, persistent proteinuria represents a spectrum from a benign disorder to a disease which can progress to end-stage renal failure.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nilay S Shah ◽  
Hongyan Ning ◽  
Amanda Perak ◽  
Norrina B Allen ◽  
John T Wilkins ◽  
...  

Introduction: Premature fatal cardiovascular disease rates have plateaued in the US. Identifying population distributions of short- and long-term predicted risk for atherosclerotic cardiovascular disease (ASCVD) can inform interventions and policy to improve cardiovascular health over the life course. Methods: Among nonpregnant participants age 30-59 years without prevalent CVD from the National Health and Nutrition Examination Surveys 2015-18, continuous 10 year (10Y) and 30 year (30Y) predicted ASCVD risk were assigned using the Pooled Cohort Equations and a 30-year competing risk model, respectively. Intermediate/high 10Y risk was defined as ≥7.5%, and high 30Y risk was chosen a priori as ≥20%, based on 2019 guideline levels for risk stratification. Participants were combined into low 10Y/low 30Y, low 10Y/high 30Y, and intermediate/high 10Y categories. We calculated and compared risk distributions overall and across race-sex, age, body mass index (BMI), and education using chi-square tests. Results: In 1495 NHANES participants age 30-59 years (representing 53,022,413 Americans), median 10Y risk was 2.3% and 30Y risk was 15.5%. Approximately 12% of individuals were already estimated to have intermediate/high 10Y risk. Of those at low 10Y risk, 30% had high 30Y predicted risk. Distributions differed significantly by sex, race, age, BMI, and education (P<0.01, Figure ). Black males more frequently had high 10Y risk compared with other race-sex groups. Older individuals, those with BMI ≥30 kg/m 2 , and with ≤high school education had a higher frequency of low 10Y/high 30Y risk. Conclusions: More than one-third of middle-aged U.S. adults have elevated short- or long-term predicted risk for ASCVD. While the majority of middle-aged US adults are at low 10Y risk, a large proportion among this subgroup are at high 30Y ASCVD risk, indicating a substantial need for enhanced clinical and population level prevention earlier in the life course.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Hooker ◽  
R A Leeuw ◽  
J Twisk ◽  
H Brolmann ◽  
J Huirne

Abstract Study question Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs. Summary answer Reproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs. What is known already The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance. Study design, size, duration This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8–12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization. Participants/materials, setting, methods Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded. Main results and the role of chance In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value &lt;0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups. Limitations, reasons for caution In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol. Wider implications of the findings As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered. Trial registration number Netherlands Trial Register NTR 3120.


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