Large Study Research Articles

Quality of Life in Children With Chronic Health Conditions and Its Contribution to Unmet Supportive Care Needs of Families.

While theoretical models have established the bidirectional relationship between health and wellbeing of parents and children with chronic health conditions (CHCs), previous work has predominantly emphasised the impact of parent functioning on child outcomes. This study examines how quality of life (QoL) domains in children with CHCs are associated with unmet supportive care needs (SCN) of their parents and explores whether these associations vary by health condition. Parents of children with congenital heart disease (CHD), type 1 diabetes (T1D) and cancer diagnosed before the age of 12 years and receiving treatment within the last 5 years were eligible. Parents recruited through charity organisations and social media platforms completed a secure, online survey via Qualtrics. The PedsQL examined child QoL across four dimensions: physical, emotional, social and school functioning. A 34-item survey assessed parents' unmet SCN in the previous month across six need domains (e.g., care and informational). Linear regressions examined associations between child QoL and unmet SCN domains and moderation analyses determined whether associations varied as a function of CHC. The study included 186 parents (age range 25-56 years) of children diagnosed with various CHCs (52% CHD; 27% T1D, 21% cancer). The child's emotional functioning was inversely related to all unmet SCN domains, social functioning was inversely related to three domains (physical and social; support; financial), school functioning was inversely related to two domains (physical and social; care), and child's physical functioning was not associated with any SCN domains. Only the association between child school functioning and unmet care needs was significantly moderated by CHC type (p < 0.05). Poorer emotional functioning in children with a CHC is a key factor in determining parents unmet SCN. Larger studies are required to replicate these findings and inform design of interventions addressing QoL and unmet SCN in families of children with common CHCs.

Intrapartum Electronic Cigarette Use and Birth Outcomes: Evidence from a Population-Based Study

The harms of combustible cigarette (CC) use in pregnancy for fetal development are well studied. Less understood are the potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (ECs). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, and vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n = 26,394), CC (n = 2216), and EC (n = 493)) were compared on birth outcomes, controlling for background differences. Controls were defined as nonsmokers of ECs or CCs. Compared to the controls, the EC group had significantly lower birth weight, while the CC group had reduced birthweight and greater rates of arterial cord pH &lt; 7.1. Compared to EC users, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests ECs are not safer alternatives to CCs and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

Empagliflozin use in cardiac transplant patients

Objectives: Sodium-glucose transport protein 2 inhibitor |(SGLT2) drugs are used to treat patients with type 2 diabetes. In additions to their beneficial metabolic effects in lowering the glaciated hemoglobin, body weight and blood pressure, these agents have shown favorable and protective effects on the heart and the kidneys. These cardio renal benefits are seen even in people without diabetes. There is little evidence on the safety and efficacy of SGLT2 inhibitors use in cardiac transplant recipients. We wanted to study the cardiac transplant recipients who used Empagliflozin for the treatment of diabetes to evaluate its safety and efficacy in this niche sub group of patients. Method: We retrospectively identified 20 patients on the cardiac transplant recipient register taking Empagliflozin (Jardiance) or Empagliflozin combined with Metformin (Synjardy). We studied the safety and efficacy parameters. Results: Our results show improvement in HBA1c, body weight and stability in serum creatinine. There was no increased risk of genitourinary infection, hypoglycemia or diabetic ketoacidosis. Conclusion: While we need larger studies in cardiac transplant patients taking Empagliflozin, our small study provides assurance that Empagliflozin is safe to use in cardiac transplant recipients.

Anti-IL-17/23 Drugs for the Treatment of Moderate-to-Severe Hidradenitis Suppurativa in Patients With Concomitant Psoriasis: A Multicenter Retrospective Study

Introduction: Psoriasis and hidradenitis suppurativa (HS) are chronic inflammatory diseases with significant overlap in their immunologic pathways, which involve cytokines such as tumor necrosis factor-alfa, interleukin (IL)-17, and IL-23. Current treatment options for HS are limited, as only adalimumab and secukinumab are approved for severe cases. Given the overlapping pathogenetic features between HS and psoriasis, anti-IL-17 and anti-IL-23 drugs could represent valuable treatments for the management of HS. Objectives: We sought to evaluate the effectiveness and safety of anti-IL-17 and anti-IL-23 drugs in patients with HS and concomitant moderate-to-severe plaque psoriasis. Methods: We conducted a multicenter retrospective study in 11 Italian Dermatology Units. The effectiveness of the drugs was evaluated by assessing the percentage of patients achieving HS Clinical Response (HiSCR) each week. Results: We enrolled 41 patients with at least 16 weeks of follow-up, with 17 of them completing 52 weeks of treatment. The most commonly prescribed anti-IL drug was secukinumab (27 patients), followed by ixekizumab (5) and guselkumab (5). The HiSCR was achieved by 39%, 74.3%, and 77.8% of patients after 16, 32, and 52 weeks, respectively. No severe adverse events (AEs) or AEs leading to discontinuation were observed during the study. The most common AE was nasopharyngitis (4 patients). Conclusion: In this real-world study, we highlight the effectiveness of anti-IL-23 and anti-IL-17 drugs in the treatment of concomitant plaque psoriasis and severe HS. Longer and larger studies are needed to further evaluate the long-term effectiveness and safety of these treatments in patients affected by HS.

Treatment of obstructive sleep apnea with CPAP improves daytime sleepiness and fatigue in cancer patients.

Fatigue and sleep disorders are prevalent in cancer patients. Obstructive sleep apnea (OSA) commonly causes excessive daytime sleepiness (EDS) and fatigue. We hypothesize that treating cancer patients with OSA using positive airway pressure (PAP) will improve EDS and fatigue. A retrospective chart review of sleep clinic visits of cancer patients with newly diagnosed OSA was performed. Epworth Sleepiness Scale (ESS) and fatigue reported at baseline and within 6 months of starting PAP therapy were compared between PAP-adherent and PAP-non-adherent patients. 65 cancer patients with OSA and ESS >10 were recommended PAP therapy, including 45 patients with fatigue. 29 patients pursued PAP therapy with 79% (n = 23) adherent at follow-up. The median baseline apnea hypopnea index (AHI) for OSA was 24.0 (interquartile range [IQR] 14.3, 32.3) and 23.8 (IQR 10.1, 42.8) events/hour among PAP-adherent and PAP-non-adherent patients, respectively (p = 0.90). Median baseline ESS was 14.0 (IQR 12.0, 17.0) among adherent and 17.0 (IQR 11.0, 17.3) among non-adherent patients (p = 0.73). The median ESS at follow-up of the adherent and non-adherent groups was 8.0 (IQR 6.0, 10.0) and 11.0 (IQR 8.0, 15.8), respectively (p = 0.08). Median ESS change was -5.0 (IQR -7.0, -4.0) in PAP adherent patients and -2.5 (IQR -5.25, -1.50) in PAP-non-adherent patients (p = 0.07). When the groups are examined separately, the median change in the PAP-adherent group was highly significant (p = 0.001), while the ESS median change in the PAP-non-adherent group was considerably less (p = 0.04). 17out of the 21 PAP-adherent patients reporting fatigue at baseline indicated improvement at follow-up. PAP therapy for OSA in cancer patients improves EDS and fatigue. Larger studies are necessary to evaluate the efficacy of PAP in improving fatigue in this population.

Exploring the Connection Between Family History of Seizures and Post-traumatic Brain Injury Seizure Types: A Retrospective Study

Background: Traumatic brain injury (TBI) is one of the most common presentations to emergency departments and is associated with seizures carrying different significance at different stages following injury. The occurrence of seizures after head injury is a recognized complication of TBI and has been demonstrated to worsen functional outcomes significantly. Despite previous studies identifying various PTS risk factors, our understanding remains limited, particularly regarding familial seizure history. Materials and Methods: A retrospective study was conducted at King Abdullah University Hospital (KAUH), Jordan, examining 1934 TBI cases from 2017 to 2023, identifying 118 patients with confirmed post-traumatic seizures. Results: This study involved 118 TBI patients, aged between 2 and 86 years (median 21.5 years), with 74.6% male and 25.4% female. A family history of seizures was reported by 23.7% of patients. Intracerebral hemorrhage (ICH) (52.5%) and subarachnoid hemorrhage (SAH) (38.1%) were the predominant trauma types. Generalized tonicclonic (GTCs) seizures (69.5%) and focal seizures (30.5%) were observed post-TBI. Among 28 patients with a family history of seizures, no evidence of association was observed between the family history and post-traumatic seizure types (GTCs or focal seizures), this was confirmed by performing Chi-square tests (p = 0.9841) and logistic regression analysis (p = 0.79). Conclusion: Our findings suggest that there is no evidence of the association between family history and post-traumatic seizure types, implying that a specialized approach for patients with positive family histories may not be warranted. Larger studies are recommended for further validation.

Bone resorption as a marker for delayed esophageal perforation post anterior cervical spine surgery: a retrospective analysis and call for increased vigilance

PurposeDelayed esophageal perforation following anterior cervical spine surgery (ACSS) is a rare but serious complication. This study is to investigate the clinical characteristics, diagnostic approaches, and treatment outcomes of delayed esophageal perforation following ACSS, with a focus on the role of bone resorption around internal fixations as a potential diagnostic indicator.MethodsWe retrospectively analyzed patients diagnosed with delayed esophageal perforation after ACSS from January 2010 to December 2023 and described their clinical characteristics, diagnostic approaches, and treatment outcomes. Through the analysis of the differences in the radiomics of patients, we identified the possible clinical signs of esophageal perforation and shared our experience in treating esophageal perforation.ResultsA total of five patients met our criteria. All five patients exhibited bone resorption around their internal fixations on radiography. Although bone resorption typically suggests local infection, none of the patients showed clear signs of neck skin infection, leading us to suspect esophageal perforation as the underlying cause. Further diagnostic procedures including CT, MRI, esophagography, and endoscopy were crucial for confirming the diagnosis of delayed esophageal perforation and assessing its severity. All patients underwent surgical intervention involving implant removal and esophageal repair using a sternocleidomastoid muscle flap transfer. All patients recovered and were discharged after treatment, with no recurrence of symptoms during follow-up.ConclusionDelayed esophageal perforation should be considered in patients with neck pain or nonspecific symptoms after ACSS, especially with bone resorption around internal fixations. Clinicians should maintain high vigilance and use multimodal imaging and endoscopy for timely diagnosis. Our study indicates a significant link between bone resorption and delayed esophageal perforation despite the limited number of cases. Highlighting this association aims to raise awareness and encourage further research. Larger studies are needed to validate our findings, improve clinical guidelines, and ultimately enhance patient outcomes in orthopedics.

Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance

Background and Aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC. Materials and Methods: Men with PC and a BMI &gt; 25 kg/m2 undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro–Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively. Results: Ten AS patients aged 62.1(±5.4) years were enrolled with an average BMI of 31.7 kg/m2 (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p &lt; 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p &gt; 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline. Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

A Risk Prediction Model for Prolonged Length of Stay After Minimally Invasive Valve Surgery.

Minimally invasive surgery determines shorter postoperative hospital length of stay (LOS) even in cardiac surgery. Potential preoperative factors affecting LOS are still not known in minimally invasive heart valve surgery (MIVS). We aimed to identify preoperative variables influencing prolonged LOS in MIVS. We reviewed 189 patients who underwent MIVS via minithoracotomy at our institution. Prolonged LOS was defined as more than 7 postoperative days. Poisson and logistic regression were used to screen the predictors. The mean postoperative LOS was 9.13 days, and 64 patients (33.9%) experienced a prolonged LOS. These patients were older, more frequently in New York Heart Association (NYHA) class III or IV, showed worse left ventricular ejection function (LVEF), and had a higher incidence of reoperation and chronic kidney disease (CKD). At univariate analysis, the most significant preoperative factors affecting prolonged LOS were age (odds ratio [OR] = 1.04), NYHA class III or IV (OR = 3.03), reduced LVEF (OR = 3.22), CKD (OR = 2.7), and redo surgery (OR = 3.6). After adjustment, the most significant preoperative factors predicting prolonged LOS were age (OR = 1.03, 95% CI: 1.01 to 1.06, P = 0.02) and redo surgery (OR = 3.33, 95% CI: 1.29 to 8.9, P = 0.01). The most important factors affecting prolonged LOS after MIVS were represented by age and redo surgery, although other preoperative characteristics such as reduced LVEF, NYHA class III or IV, and CKD play a significant role in delaying recovery after MIVS. Further larger studies are needed to better identify potential preoperative predictors of prolonged LOS after MIVS.

Advanced quantitative magnetic resonance imaging of lower extremity muscle microtrauma after marathon: a mini review

This article reviews the existing literature and outlines recent advances in quantitative Magnetic Resonance Imaging (MRI) techniques for the assessment of lower extremity muscle microtrauma following a marathon. Single-modality quantitative MRI techniques include T2 mapping to assess the dynamics of muscle inflammatory edema and variability at the site of injury, Diffusion Tensor Imaging (DTI) to detect subclinical changes in muscle injury, Intravoxel Incoherent Motion (IVIM) imaging to provide simultaneous information on perfusion and diffusion in muscle tissue without the need for intravenous contrast, and Magnetic Resonance Spectroscopy (MRS) to noninvasively detect intramyocellular lipid (IMCL) content in muscle before and after marathon exercise to explain the use of fatty acids as an energy source in skeletal muscle during long-distance running. As well as Chemical Exchange Saturation Transfer (CEST) is particularly suitable for detecting changes in free creatine, pH values and lactate concentrations in muscles before and after exercise, providing a more detailed picture of muscle physiology and chemistry. These metabolic MRI methods enhance the understanding of biochemical alterations occurring in muscles pre- and post-exercise. Multimodal techniques combine different modalities to provide a comprehensive evaluation of muscle structural and functional changes. These advanced techniques aim to better assess microtrauma and guide clinical treatment, though further validation with larger studies is needed to establish their potential over traditional qualitative methods.

Added value of body MRI to detect primary abdominal malignancies in the diagnostic work-up of patients with adenocarcinoma of unknown primary

Abstract Purpose This study aimed to evaluate the added benefit of body MRI (covering the chest, abdomen, and pelvis) to detect the primary tumour in patients with adenocarcinoma of unknown primary (ACUP) and a suspected abdominal malignancy in whom previous diagnostic work-up with CT and/or FDG-PET/CT did not yield a primary tumour diagnosis. Methods Thirty ACUP patients with a suspected primary tumour in the abdomen/pelvis (based on pathology and/or pattern of disease) underwent MRI (T2-weighted, DWI, pre- and post-contrast T1-weighted) after completion of their initial diagnostic work-up with CT and/or PET/CT. Effects of MRI to establish a primary tumour diagnosis (and to detect additional metastatic sites) were documented. Integration of all available imaging data, additional diagnostic procedures (e.g., endoscopy), histopathology, and whole genome sequencing served as the composite standard of reference. Results MRI rendered a possible primary tumour diagnosis in 16/30 (53%) cases, which aligned with the final clinical diagnosis in 9/16 (56%) of these cases, thus resulting in a confirmed primary tumour diagnosis in 30% of our total patient cohort. These included four gastrointestinal, two hepatobiliary, one pancreatic, one ovarian and one breast cancer. MRI revealed extra metastatic sites in five patients (17%). Conclusion MRI can be of added value in the diagnostic work-up of ACUP patients with a suspected primary tumour originating from the abdomen or pelvis, in particular to detect gastrointestinal or hepatobiliary malignancies. Larger studies are needed to confirm these results and identify specific ACUP patients that are most likely to benefit from MRI. Key Points QuestionCan body MRI help identify the primary tumour in patients with adenocarcinoma of unknown primary (ACUP)? FindingsIn this pilot of n = 30 ACUP patients with clinically suspected abdominal malignancies, body MRI was able to establish the primary tumour in 30% of cases. Clinical relevanceBody MRI can be of added value (as an adjunct to CT and/or PET/CT) in the diagnostic work-up of ACUP patients with a suspected primary tumour originating from the abdomen or pelvis, especially to detect gastrointestinal or hepatobiliary malignancies.

Machine Learning Model Predictors of Intrapleural tPA and DNase Failure in Pleural Infection: A Multicenter Study.

Intrapleural enzyme therapy (IET) with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has been shown to reduce the need for surgical intervention for complicated parapneumonic effusion/empyema (CPPE/empyema). Failure of IET may lead to delayed care, and increased length of stay. The goal of this study was to identify risk factors for failure of IET. We performed a multicenter, retrospective study of patients who received IET for the treatment of CPPE/empyema. Clinical and radiological variables at the time of diagnosis were included. We compared four different machine learning classifiers (L1-penalized logistic regression, support vector machine (SVM), XGBoost and LightGBM) by multiple bootstrap-validated metrics, including F-beta to demonstrate model performances. 466 participants who received IET for pleural infection were included from five institutions across the United States. Resolution of CPPE/empyema with IET was achieved in 78% (n=365). SVM performed superior with median F-beta of 56%, followed by L1-penalized logistic regression, LGBM and XGBoost. Clinical and radiological variables were graded based on their ranked variable importance. The top two significant predictors of IET failure using SVM were the presence of an abscess/necrotizing pneumonia (17%) and pleural thickening (13%). Similarly, LightGBM identified abscess/necrotizing pneumonia (35%) and pleural thickening (26%) and XGBoost indicated pleural thickening (36%) and abscess/necrotizing pneumonia (17%) as the most significant predictors of treatment failure. Predictors identified by L1-penalized logistic regression model were pleural thickening (18%) and pleural fluid LDH (9%). The presence of abscess/necrotizing pneumonia and pleural thickening consistently ranked among the strongest predictors of IET failure in all machine learning models. The difference in rankings between models may be a consequence of the different algorithms used by each model. These results indicate that the presence of abscess/necrotizing pneumonia, and pleural thickening may predict IET failure. These results should be confirmed in larger studies.

Feasibility and early outcomes of atrial septal defect prostheses use for percutaneous closure of widely open patent foramen ovale

Abstract Background The efficient closure of patent foramen ovale (PFO) with short canal length and large width, usually associated with atrial septal aneurysm (ASA), remains challenging. These cases frequently require the use of larger PFO devices to avoid the risk of device embolism at the cost of a higher rate of residual shunting, mostly due to interdisk spacing. The use of atrial septal defect (ASD) prosthesis could be useful in these patients. Purpose To describe feasibility and early outcomes of the use of ASD device for percutaneous closure of widely open PFO representing an "ASD-like anatomy". Methods Since January 2022 in a high volume French university center, we started to use ASD device for percutaneous closure of selected cases of PFO with complex anatomy as mainly defined by a sheathed width of PFO ≥ 5 mm and sheathed canal length ≤ 10 mm (Figure 1) facing major per-operative residual shunt with PFO prostheses in some patients. In addition to the descriptive results, we compared this ASD device subgroup with a cohort of patients with similar anatomy but previously treated in our center with PFO device. All available transesophageal echocardiography (TEE) examinations were reviewed. The main objective was to describe the feasibility of the procedure (success and safety), the secondary endpoint was immediate post-procedural moderate to severe residual right-to-left shunt (RLS), defined as ≥ 10 bubbles in the left atrium within 3 cardiac cycles after transfemoral agitated saline injection. Results A total of 65 patients was treated with ASD devices, procedural success was achieved in all patients with a low rate (4,2%) of intrahospital complications (two supraventricular arrythmia, one anaphylactic shock and one minor laryngeal injury) and without device embolism. As compared with a cohort of 127 patients of similar anatomy treated with PFO device, patients in the ASD device group had more complex characteristics especially higher mean sheathed PFO width and shorter mean sheathed PFO canal length. Immediate post-procedural residual moderate to severe RLS did not differ significatively between groups (Table 1). No or minimal shunting was observed in 91% and 92% of cases (p=NS) but the three patients with severe RLS were all in the PFO device group. Conclusion Percutaneous closure of "ASD-like" PFO with ASD prostheses is feasible and safe. Larger studies and longer follow-ups are now required to confirm the expected improved sealing effect with this strategy.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS&amp;gt;29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

Left atrial function predicts long-term outcome in hypertension and diabetes across genders

Abstract Introduction In the last decade, peak atrial longitudinal strain (PALS) was ascertained to be superior to conventional echocardiographic indices for secondary cardiovascular (CV) prevention. Purpose Standard and advanced echocardiography including PALS was evaluated to find predictors of prognosis in patients with arterial hypertension and/or diabetes for the optimization of primary CV prevention. Methods Hypertensive and/or diabetic patients &amp;gt;40 years old and in sinus rhythm who underwent a complete cardiological evaluation at our centre in 2008-2015 were retrospectively included. Personal history, physical examination, standard and advanced (speckle tracking) echocardiographic data were collected. The exclusion criteria were previous cv events or cardiac surgery, active pacemaker, more than moderate valvular regurgitation and/or stenosis, missing informed consent. All patients were followed up for a mean time of 11.2±1.3 years for the development of first atrial fibrillation (AF) episode, congestive heart failure hospitalization, transient ischemic attack, stroke, myocardial infarction/coronary revascularization, and CV death. Univariate and multivariable stepwise Cox regressions were performed to estimate Hazard Ratio (HR). Kaplan Meier curves (KM) compared the survival between patients with different ranges of Global PALS. Log-rank test was performed to compare the KM curves. Results This retrospective study included 292 adults (mean age 63.0±9.0 years, 50% female), among which 210 hypertensives and 67 diabetics. Mean left ventricular (LV) ejection fraction (EF) was 58.2±4.9%, mean GLS was -17.0±6.6%, mean left atrial volume was 52.9±24.9ml and mean PALS 29.7±11.1%. During follow up, 110 patients developed at least one cv event: 52 all-cause deaths, 28 CV deaths, 30 heart failure admissions, 31 first AF episode, 18 TIA/strokes, 25 myocardial infarction/revascularization. Dividing the population according to events occurrence, patients with events had similar EF (p= 0.06), while being older (65.8±9.6 vs 61.3±9.0 years) and with a worse diastolic function (E/E’ ratio 10.6±5.0 vs 8.7±3.6), LV longitudinal strain (GLS, -17.7±2.9 vs -15.7±3.4%) and PALS (34.6±9.9 vs 21.6±7.7%, all p &amp;lt;0.001). From univariate statistical analysis, age, E/E’, PAPs, GLS and PALS were all predictors of events, but only age (HR 1.03, p=0.03) and PALS (PALS&amp;lt;22.5% HR 18.99 and PALS 22.5-30 HR 7.68, both p&amp;lt;0.001) remained independently associated with outcome at multivariate analysis. Patients with PALS&amp;lt;22.5 have an event-free survival of 82.4% at 1 year, 49.8% at 5 years and 25.3% at 10 years compared to 100% at 1 year, 98.5% at 5 years and 92.5% at 10 years if PALS PALS&amp;gt;30% (Fig.1). The same results were confirmed in female population (Fig.2). Conclusions If confirmed by larger studies, PALS could be a quick, feasible and reliable part of cardiologic evaluation for prognostic stratification in primary CV prevention in hypertensive and/or diabetic patients.Fig. 1Fig. 2

True-MAD and pseudo-MAD in consecutive patients undergoing cardiovascular magnetic resonance

Abstract Background Mitral annulus disjunction (MAD) is a controversial imaging entity with uncertain clinical significance, which has been either considered a pathological entity potentially related to mitral valve prolapse (MVP) and sudden cardiac death or, on the contrary, a benign finding in normal hearts. Cardiovascular magnetic resonance (CMR) is poised to be the ideal imaging modality to assess MAD. Recently, a distinction between pseudo-MAD, present only in systole and secondary to juxtaposition of the billowing posterior leaflet on the adjacent left atrial wall, and true-MAD, where the insertion of the posterior leaflet is clearly displaced on the atrial wall either in diastole or in systole, has been suggested. Purpose We aimed to investigate the prevalence of pseudo-MAD and true-MAD in consecutive patients undergoing clinically-referred CMR. Methods This was a single-center retrospective study including consecutive patients referred to CMR from September 2023 to November 2023. Patients with feasible MAD assessment were included. MAD was defined as a ≥1 mm displacement between the left atrial wall-mitral valve leaflet junction hinge and the top of the left ventricular wall, measured from cine-CMR images in the three long-axis views. Pseudo-MAD and true-MAD were defined according to the presence of MAD only in systole or both in systole and diastole, respectively. MVP was defined as a systolic displacement ≥2 mm of one or both mitral valve leaflets above the annulus in 3-chamber view. Results Two-hundred-ninety patients (mean age 57±18 years; 181 men, 62%) were included. MVP and MAD were respectively found in 24 (8%) and 145 (50%) patients, of which 98 (34%) with true-MAD and 47 (16%) with pseudo-MAD. In all measurements, systolic MAD (2.6±1.3 mm) resulted equal to or greater than diastolic MAD (2.2±1.1 mm). The most frequent MAD location was the inferior wall in the two-chamber view (42%), whereas the rarest one was the inferolateral wall in the three-chamber view (17%). In patients with MVP, the prevalence of MAD was higher when considering all long-axis views (22 patients, 92%), of which 50% presented with true-MAD and 50% with pseudo-MAD. The extent of pseudo-MAD and true-MAD were both greater in patients with MVP (4.2±1.5 mm and 3.0±1.6 mm, respectively) than in those without MVP (2.3±1.0 and 2.1±0.9 mm; p&amp;lt;0.001 and p=0.007, respectively) in all locations. At the level of the inferolateral wall, the prevalence of MAD was 71% vs. 12% (p&amp;lt;0.001) in patients with vs. without MVP. Conclusions The presence of true-MAD was a common imaging finding in consecutive patients undergoing CMR, thus not resulting in a distinctive abnormal feature related to MVP or sudden cardiac death. Patients with MVP showed higher prevalence and extent of true-MAD and pseudo-MAD in all locations, in line with greater degeneration of the mitral annulus. Larger studies are needed to identify potential malignant characteristics of MAD.True-MAD (A,B) and pseudo-MAD (C,D).

Bioprosthetic versus mechanical prostheses in patients aged 50 to 70 years undergoing aortic valve replacement surgery: outcomes analysis from propensity score matching

Abstract Introduction Despite increasing use of bioprosthetic surgical aortic valve replacement (bAVR) in patients ≤70 years [1, 2], the relative benefits compared to mechanical valve replacement (mAVR) remain uncertain [3, 4]. Purpose The current study aims to compare mortality and other important clinical endpoints by prosthesis type for patients aged 50-70 years who received an AVR in a well-characterised Australian cohort. Methods A retrospective cohort study was designed utilising the WAVES Patient Registry and incorporating linked administrative outcome data including all patients who had an AVR in Western Australian public hospitals between 2010-2020. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, separately and combined with non-fatal myocardial infarction and non-fatal stroke (MACE), major bleeding, and days alive and out of hospital (DAOH). Outcomes were compared based on a propensity-matched analysis (including demographics, biometrics, and clinical characteristics). Results Within the initial cohort of 727 patients undergoing surgical AVR (mean age = 63 ± SD 6), a propensity-matched cohort identified 151 patients each with bAVR (mean age = 61 ± 4) and mAVR (mean age = 60 ± 5). Patients who received mAVR versus bAVR had improved all-cause survival (Hazard Ratio [HR] 0.50; 95% CI 0.25-0.99) but increased risk of major bleeding (HR 4.85; 95% CI 1.57-14.98). There were no significant differences in CV mortality (HR 0.58; 95% CI 0.19-1.74), MACE (HR 0.59; 95 % CI 0.32-1.07), or DAOH by prosthesis type (P = 0.452). Conclusions Patients aged 50-70 years who underwent mAVR had lower risk of all-cause mortality compared with bAVR, despite higher bleeding risk. Although risks of CV mortality and MACE were lower in mAVR, statistical significance was not reached, likely due to the small sample size. Larger studies are necessary to confirm these findings, which have important clinical implications.

The Significance of the Myocardial Performance Index and Fetal Doppler Abnormalities in Growth-Restricted Fetuses: A Systematic Review of the Literature

Introduction: This review aims to investigate the clinical implications of using the myocardial performance index (MPI), obtained through tissue Doppler imaging (TDI) and spectral Doppler, in assessing fetal cardiac function in growth-restricted fetuses. It explores the MPI’s potential in predicting adverse perinatal outcomes and its utility when combined with conventional pulsed-wave Doppler assessments for enhanced fetal well-being evaluations. Material and Methods: A systematic search of PubMed and Google Scholar databases spanning from 2004 to 2023 was conducted to identify pertinent articles on the MPI’s clinical application in managing growth-restricted fetuses. Inclusion criteria followed the Fetal Medicine Barcelona definition of fetal growth restriction (FGR) to mitigate study group heterogeneity. The research sources were PubMed and Google Scholar databases, and the review was conducted without any specific clinical or laboratory setting. Only articles meeting the inclusion criteria for FGR, as per the Fetal Medicine Barcelona definition, were considered. Six studies meeting these criteria were included in the review. The review analyzed the correlation between MPI values and conventional Doppler parameters, investigating the progression of myocardial function impairment and its association with the risk of fetal demise. The primary outcome measures included the relationship between MPI values, fetal well-being, and the potential for prenatal cardiac dysfunction in growth-restricted fetuses. Results: The findings indicate that as conventional Doppler parameters deteriorate, MPI values increase, suggesting progressive myocardial dysfunction. The MPI may cross the 95th percentile before abnormal flow in the ductus venosus and aortic isthmus, highlighting the potential for diastolic dysfunction preceding hypoxia in growth-restricted fetuses. Elevated MPI levels were observed in both growth-restricted and small-for-gestational-age (SGA) fetuses, indicating prenatal cardiac impairment. The strong association between an abnormal MPI and perinatal mortality has been shown for early FGR. Conclusions: MPI alterations appear to precede abnormal Doppler parameters in early- and late- onset FGR, potentially indicating diastolic dysfunction preceding hypoxia. Additionally, the MPI correlates with the risk of fetal demise. However, larger studies are needed to establish its sensitivity and specificity. Furthermore, the significance of prenatal cardiac impairment in some SGA fetuses raises questions about its potential impact on perinatal outcomes and cardiovascular programming.

Magnetic resonance lymphangiography abnormalities as extracardiac biomarkers of pulmonary hypertension and functional phenotype in Fontan-Kreutzer univentricular circulation.

Lymphatic abnormalities have been documented on magnetic resonance lymphangiography in patients with functionally univentricular circulation. The aim of this study is to evaluate associations between findings on magnetic resonance lymphangiography, cardiac catheterisation and functional phenotype in patients with Fontan-Kreutzer circulation. Between January 2017 and October 2019, seven patients with Fontan-Kreutzer circulation (16.57 ± 7.10 years) were enrolled following ethical committee approval and attainment of informed consent. Clinical data, consecutive magnetic resonance imaging and cardiac catheterisation findings were reviewed. Qualitative lymphatic abnormality types were defined as: 1 - Little or none; 2 - Localised to the supraclavicular region; 3 - Extending into the mediastinum; and 4 - Extending into the lung. Pulmonary hypertension was defined as a transpulmonary gradient > 6 mmHg. Quantitative data were assessed using Mann-Whitney U tests, and p < 0.05 was considered statistically significant. Patients with lymphatic abnormalities categorised type 1 or 2 and transpulmonary gradient ≤ 6 mmHg had a normal functional phenotype, while those with type 3 or 4 and transpulmonary gradient > 6 mmHg had a failing functional phenotype. Magnetic resonance lymphangiography in patients with Fontan-Kreutzer circulation and pulmonary hypertension revealed lymphatic abnormalities types 3-4, indicative of a failing functional phenotype compared to patients without pulmonary hypertension. If validated in larger studies, these results suggest the potential utility of this extracardiac biomarker for improving risk stratification. Integration of lymphangiography and transpulmonary gradient with functional class, atrioventricular valve function, and ejection fraction allowed for the categorisation of three distinct functional phenotypes, which may be valuable for future analyses.

High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)

Abstract Background Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a). Aim To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a). Methods Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes. Results During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction &amp;gt;50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a). Conclusion Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.