Background Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was ...gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live-borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed. Methods and Results Neonates with hypoplastic left heart syndrome with aortic atresia born 1990-2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox-logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis. Conclusions We observed a decrease in incidence of live-borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live-borns who underwent surgery increased between time periods.
Aims
This study aimed to evaluate the outcome and prognostic factors in patients with dilated cardiomyopathy (DCM) and long‐standing heart failure (LDCM) vs. recent‐onset heart failure (RODCM).
...Methods and results
We compared 2019 patients with RODCM (duration <6 months, mean age 58.6 years, 70.7% male) with 1714 patients with LDCM (duration ≥6 months, median duration 3.5 years, mean age 62.5 years, 73.7% male) included in the Swedish Heart Failure Registry in the years 2003–16. Outcome measures were all‐cause, cardiovascular (CV), and non‐CV death and hospitalizations; heart transplantation; and a combined outcome of all‐cause death, heart transplantation, or heart failure (HF) hospitalization. Multivariable risk factor analyses were performed for the combined endpoint. All outcomes were more frequent in LDCM than in RODCM. The multivariable‐adjusted hazard ratios (HRs) (95% confidence interval) for LDCM vs. RODCM were 1.56 (1.34–1.82), P < 0.0001, for all‐cause death over a median follow‐up of 4.2 and 5.0 years, respectively; 1.67 (1.36–2.05), P < 0.0001, for CV death; 2.12 (1.14–3.91), P < 0.0001, for heart transplantation; 1.36 (1.21–1.53), P < 0.0001, for HF hospitalization; and 1.37 (1.24–1.52), P < 0.0001, for the combined outcome. A propensity score‐matched analysis yielded similar results. CV death was the main cause of mortality in LDCM and was higher in LDCM than in RODCM (P < 0.0001). Almost all co‐morbidities were significantly more frequent in LDCM than in RODCM, and the mean number of co‐morbidities increased significantly with increased duration of disease, also after age adjustment. Age, New York Heart Association functional class, ejection fraction, and left bundle branch block were prognostically adverse. The only co‐morbidity associated with the combined outcome regardless of HF duration was diabetes, in LDCM HR 1.34 (1.15–1.56), P = 0.0002 and in RODCM HR 1.29 (1.04–1.59), P = 0.018. Male sex HR 1.38 (1.18–1.63), P < 0.0001 and aspirin use HR 1.33 (1.14–1.55), P = 0.0004 carried increased risk only in RODCM. Heart rate ≥75 b.p.m. HR 1.20 (1.04–1.37), P = 0.01, atrial fibrillation HR 1.24 (1.08–1.42), P = 0.0024, musculoskeletal or connective tissue disorder HR 1.36 (1.13–1.63), P = 0.0014, and diuretic therapy HR 1.40 (1.17–1.67), P = 0.0002 were prognostically adverse only in LDCM.
Conclusions
This nationwide study of patients with DCM demonstrates that longer disease duration is associated with worse prognosis. Co‐morbidities are more common in long‐standing HF than in recent‐onset HF and are associated with worse outcome. With the increased survival seen in the last decades, our results highlight the importance of careful attention to co‐morbid conditions in patients with DCM.
Background Low income and short education have been found to be independently associated with inferior survival after coronary artery bypass grafting (CABG), whereas the use of secondary prevention ...medications is associated with improved survival. We investigated whether underusage of secondary prevention medications contributes to the inferior long-term survival in CABG patients with a low income and short education. Methods and Results Patients who underwent CABG in Sweden between 2006 to 2015 and survived at least 6 months after discharge (n=28 448) were included in a population-based cohort study. Individual patient data from 5 national registries, including the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry, covering dispensing of secondary prevention medications (statins, platelet inhibitors, β-blockers, and RAAS inhibitors), socioeconomic factors, patient characteristics, comorbidity, and long-term mortaity were merged. All-cause mortality risk was estimated using multivariable Cox regression models adjusted for patient characteristics, baseline comorbidities, time-updated secondary prevention medications, and socioeconomic status. Long-term mortality was higher in patients with a low income and short education. Statins and platelet inhibitors were dispensed less often to patients with a low income, both at baseline and after 8 years. The decline in dispensing over time was steeper for low-income patients. Short education was not associated with reduced dispensing of any secondary prevention medication. Use of statins (adjusted hazard ratio=0.57 95% CI, 0.53-0.61), RAAS inhibitors (adjusted hazard ratio=0.78 0.73-0.84), and platelet inhibitors (adjusted hazard ratio=0.74 0.68-0.80) were associated with reduced long-term mortality irrespective of socioeconomic status. Conclusions Secondary prevention medications are dispensed less often after CABG to patients with low income. Underusage of secondary prevention medications after CABG is associated with increased mortality risk independently of income and extent of education.
Aims
To study clinical phenotype, prognosis for all‐cause and cardiovascular (CV) mortality and predictive factors in patients with incident heart failure (HF) after aortic valvular intervention ...(AVI) for aortic stenosis (AS).
Methods and results
In this retrospective, observational study we included patients from the Swedish Heart Failure Registry (SwedeHF) recorded 2003–2016, with AS diagnosis and AVI before HF diagnosis. The AS diagnosis was established according to International Classification of Diseases 10th revision (ICD‐10) codes, thus without information concerning clinical or echocardiographical data on the aortic valve disease. The patients were divided into two subgroups: left ventricular ejection fraction (LVEF) ≥ 50% (AS‐HFpEF) and <50% (AS‐HFrEF). We individually matched three controls with HF from the SwedeHF without AS (control group) for each patient. Baseline characteristics, co‐morbidities, survival status and outcomes were obtained by linking the SwedeHF with two other Swedish registries. We used Kaplan–Meier curves to present time to all‐cause mortality, cumulative incidence function for time to CV mortality and Cox proportional hazards model to evaluate the relative difference between AS‐HFrEF and AS‐HFpEF and AS‐HF and controls. The crude all‐cause mortality was 49.0%, CV mortality 27.9% in AS‐HF patients, respectively 44.7% and 26.6% in matched controls. The adjusted risk for all‐cause mortality and CV mortality was similar in HF, regardless of LVEF vs. controls. No significant difference in factors predicting higher all‐cause mortality was observed in AS‐HFrEF vs. AS‐HFpEF, except for diabetes (only in AS‐HFrEF), with statistically significant interaction predicting death between the two groups.
Conclusions
In this nationwide SwedeHF study, we characterized incident HF population after AVI. We found no significant differences in all‐cause and CV mortality compared with general HF population. They had virtually the same predictors for mortality, regardless of LVEF.
Background
Despite a decline in mortality rates from cardiovascular disease (CVD) in the past few decades, the burden of CVD in a contemporary population remains inadequately addressed. Therefore, ...this study was aimed to investigate secular trends in mortality from coronary artery disease and all‐cause mortality over 2 decades, by comparing 2 cohorts of men born 30 years apart and evaluate the prediction of the risk of CVD and all‐cause death in a contemporary random sample of Swedish men.
Methods and Results
Two cohorts of randomly selected men born in 1913 (855 men) and 1943 (798 men) were first examined at age 50 in 1963 and 1993, respectively, and followed longitudinally over 21 years. All‐cause mortality and coronary artery disease death were lower in 50‐ to 71‐year‐old men born in 1943 compared with those born in 1913, with unadjusted hazard ratios of 0.57 (0.45–0.71) and 0.34 (0.22–0.53), respectively. After adjustment for risk factors (smoking, serum cholesterol, hypertension, systolic blood pressure, diabetes mellitus, body mass index, and physical activity), the differences between the cohorts remained significant for coronary artery disease, hazard ratios 0.57 (0.34–0.94), P=0.029, but not for all‐cause mortality hazard ratios 0.82 (0.62–1.07), P=0.14. However, the rate of CVD events during follow‐up was still high (30.7%) for the men born in 1943. No statistically significant interaction by birth cohort in contribution of risk factors to death was found between 2 cohorts except physical inactivity.
Conclusions
Despite a marked reduction in the rate of coronary artery disease death over the past 30 years, the burden of CVD events and all‐cause mortality remains high. Therefore, intensified efforts to modify contributing risk factors are still required.
Nutritional deprivation occurring in most preterm infants postnatally can induce hyperglycemia, a significant and independent risk factor for suppressing physiological retinal vascularization (Phase ...I retinopathy of prematurity (ROP)), leading to compensatory but pathological neovascularization. Amino acid supplementation reduces retinal neovascularization in mice. Little is known about amino acid contribution to Phase I ROP. In mice modeling hyperglycemia-associated Phase I ROP, we found significant changes in retinal amino acids (including most decreased L-leucine, L-isoleucine, and L-valine). Parenteral L-isoleucine suppressed physiological retinal vascularization. In premature infants, severe ROP was associated with a higher mean intake of parenteral versus enteral amino acids in the first two weeks of life after adjustment for treatment group, gestational age at birth, birth weight, and sex. The number of days with parenteral amino acids support independently predicted severe ROP. Further understanding and modulating amino acids may help improve nutritional intervention and prevent Phase I ROP.
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•Hyperglycemia altered amino acid levels in neonatal mouse retinas•Parenteral L-isoleucine suppressed retinal vessel growth in hyperglycemic mouse retinas•Parenteral amino acid in preterm infants correlated with ROP requiring treatment
Disease; Biological sciences
Naproxcinod, a cyclooxygenase-inhibiting nitric oxide donator antiinflammatory drug, was evaluated in this phase 2, double-blind, randomized, parallel group study to determine its optimal dose in ...patients with osteoarthritis (OA).
In total 543 patients with OA of the hip or knee were randomized to receive naproxcinod 750 mg once daily (qd), 750 mg twice daily (bid), 1125 mg bid, rofecoxib 25 mg qd, or placebo for 6 weeks. The primary efficacy variable was the within-patient change from baseline to the average of Weeks 4 and 6 in WOMAC pain subscale score. Treatment-group differences were compared using ANCOVA with factors for treatment and country, and baseline pain subscale score as a covariate. Safety endpoints included vital signs and adverse events. Treatment-group differences in mean change from baseline to Week 6 in systolic blood pressure (SBP) were compared using an ANCOVA with treatment and country as fixed factors and baseline SBP as covariate.
All active treatments showed statistically significant reductions in WOMAC pain score compared to placebo (p<or=0.02). Naproxcinod was well tolerated. The 750 mg bid dose appeared to have the best balance of benefit versus safety. All 3 naproxcinod doses showed a reduction in SBP, while an increase was shown for rofecoxib. The changes for the naproxcinod groups were statistically significantly better compared to rofecoxib (p<or=0.02).
This dose-finding study identified naproxcinod 750 mg bid as the upper dose for further therapeutic confirmatory clinical trials. Naproxcinod at all doses decreased mean SBP compared to an increase with rofecoxib.
ObjectiveThe current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales ...(original: ROP-ActS and modified: mROP-ActS), describing increasing severity of ROP, versus the categorical variables severe ROP, stage, zone and plus disease were evaluated as discriminators of the effect of an ROP preventive treatment.Methods and analysisThe Mega Donna Mega trial investigated ROP in infants born <28-week gestational age (GA), randomised to arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation or no supplementation. Of 207 infants, 86% with finalised ROP screening were included in this substudy. ROP-ActS versus standard variables were evaluated using Fisher’s non-parametric permutation test, multivariable logistic and linear regression and marginal fractional response models.ResultsThe AA:DHA group (n=84) and the control group (n=93) were well balanced. The maximum ROP-ActS measurement was numerically but not significantly lower in the AA:DHA group (mean: 4.0 (95% CI 2.9 to 5.0)) versus the control group (mean: 5.3 (95% CI 4.1 to 6.4)), p=0.11. In infants with any ROP, the corresponding scale measurements were 6.8 (95% CI 5.4 to 8.2) and 8.7 (95% CI 7.5 to 10.0), p=0.039. Longitudinal profiles of the scale were visually distinguished for the categories of sex and GA for the intervention versus control.ConclusionsThe preventive effect of AA:DHA supplementation versus no supplementation was better discriminated by the trial’s primary outcome, severe ROP, than by ROP-ActS. The sensitivity and the linear qualities of ROP-ActS require further validations on large data sets and perhaps modifications.Trial registration numberNCT03201588.
Abstract
Background
Female sex is known to have increased perioperative mortality in cardiac surgery. Studies reporting effects of sex on outcome following surgical repair for acute Type A aortic ...dissection (ATAAD) have been limited by small cohorts of heterogeneous patient populations and have shown diverging results. This study aimed to compare perioperative characteristics, operative management, and postoperative outcome between sexes in a large and well-defined cohort of patients operated for ATAAD.
Methods
The Nordic Consortium for Acute Type A Aortic Dissection study included patients with surgical repair of ATAAD at eight Nordic centers between January 2005 and December 2014. Independent predictors of 30-day mortality were identified using multivariable logistic regression.
Results
Females represented 373 (32%) out of 1,154 patients and were significantly older (65 ± 11 vs. 60 ± 12 years,
p
< 0.001), had lower body mass index (25.8 ± 5.4 vs. 27.2 ± 4.3 kg/m
2
,
p
< 0.001), and had more often a history of hypertension (59% vs. 48%,
p
= 0.001) and chronic obstructive pulmonary disease (8% vs. 4%,
p
= 0.033) compared with males. More females presented with DeBakey class II as compared with males with dissection of the ascending aorta alone (33.4% vs. 23.1%,
p
= 0.003). Hypothermic cardiac arrest time (28 ± 16 vs. 31 ± 19 minutes,
p
= 0.026) and operation time (345 ± 133 vs. 374 ± 135 minutes,
p
< 0.001) were shorter among females. There was no difference between the sexes in unadjusted intraoperative death (9.1% vs. 6.7%,
p
= 0.17) or 30-day mortality (17.7% vs. 17.4%,
p
= 0.99). In a multivariable analysis including perioperative factors influencing mortality, no difference was found between females and males in 30-day mortality (odds ratio: 0.92, 95% confidence interval: 0.62–1.38,
p
= 0.69).
Conclusions
This study found no association between sex and early mortality following surgery for ATAAD, despite females being older and having more comorbidities, yet also presenting with a less widespread dissection than males.
Background and purpose: Mineralocorticoid receptor antagonists (MRAs) have been shown in clinical trials to improve outcomes in heart failure with reduced ejection fraction (HFrEF). Yet, it is still ...uncertain how effective they are in real-world patients with HFrEF. This study aimed to investigate the association between MRAs and outcomes in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Methods: Patients diagnosed with HFrEF were included from the SwedeHF spanning from 2003 to 2020. Enrollment was based on medication dispensation within 3 months before and 6 months after the index date recorded in the register. Endpoints included all-cause mortality, cardiovascular death, and hospital re-admissions, tracked from the index date until censoring or occurrence of an event. Results: Of 47,103 patients identified through the SwedeHF with HFrEF, 22,368 individuals were not treated with MRA (referred to as MRA naive patients), 21,893 were treated with MRA at a dosage of 25 mg, and 1,423 were treated with MRA at 50 mg once daily. In the overall cohort, the administration of MRA at 25 mg was associated with modest reductions in the risk of all-cause mortality (hazard ratio: 0.92 0.89–0.95, P < 0.0001) and cardiovascular death (hazard ratio: 0.93 0.89–0.98, P < 0.01) compared to the MRA naive group. However, both dosages of MRA (25 and 50 mg) were associated with a slight increase in the risk of hospital re-admissions due to heart failure 10% compared to MRA naive patients. These findings were consistent when examining a propensity score-matched cohort. Interaction analysis showed a significantly improved survival rate for patients receiving MRA at 25 mg compared to MRA naive individuals, particularly among those with an estimated glomerular rate ≥30 mL/min/1.73 m 2 across all patients and in those aged 70 years and above. Conclusions: The administration of MRA treatment at 25 mg once daily was linked to a modestly improved survival in a real-life HFrEF population, with even more pronounced benefits observed within a specific subgroup. This finding highlights the importance of personalized medicine in providing customized therapeutic advantages.
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