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Pubblicazioni recenti - cardiac disease
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Examining anti-inflammatory therapies in the prevention of cardiovascular events: protocol for a systematic review and network meta-analysis of randomised controlled trials.
BMJ Open2022 Jun;12(6):e062702. doi: 10.1136/bmjopen-2022-062702.
Boczar Kevin Emery, Shin Sheojung, Bezzina Kathryn A, Geejo Aishwarya, Pearson Alexander Liam, Shahab Saba, Fehlmann Christophe A, Visintini Sarah, Beanlands Rob, Wells George A,
Abstract
INTRODUCTION:
Inflammation is emerging as an important risk factor for atherosclerotic cardiovascular disease and has been a recent target for many novel therapeutic agents. However, comparative evidence regarding efficacy of these anti-inflammatory treatment options is currently lacking.
METHODS AND ANALYSIS:
This systematic review will include randomised controlled trials evaluating the effect of anti-inflammatory agents on cardiovascular outcomes in patients with known cardiovascular disease. Studies will be retrieved from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC and conference abstract handsearching. No publication date or language restrictions will be imposed. Eligible interventions must have some component of anti-inflammatory agent. These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA (darapladib) and sPLA (varespladib). The primary outcomes will include major adverse cardiac events (MACE), and each individual component of MACE (myocardial infarction, stroke and cardiovascular death). Key secondary outcomes will include unstable angina, heart failure, all-cause mortality, cardiac arrest and revascularisation. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Network meta-analysis based on the random effects model will be conducted to compare treatment effects both directly and indirectly. The quality of the evidence will be assessed with appropriate tools including the Grading of Recommendations, Assessment, Development and Evaluation profiler or Confidence in Network Meta-Analysis tool.
ETHICS AND DISSEMINATION:
Ethics approval is not required for this systematic review. The findings will be disseminated through a peer-reviewed journal.
PROSPERO REGISTRATION NUMBER:
CRD42022303289.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Serial Left and Right Ventricular Strain Analysis in Patients Recovered from COVID-19.
J Am Soc Echocardiogr2022 Jun;():. doi: S0894-7317(22)00310-8.
Young Kathleen A, Krishna Hema, Jain Vaibhav, Hamza Izhan, Scott Christopher G, Pellikka Patricia A, Villarraga Hector R,
Abstract
BACKGROUND:
Strain analysis of transthoracic echocardiography (TTE) is a sensitive tool to detect myocardial dysfunction in those affected by COVID-19. Consideration of pre-existing cardiovascular disease is important in detecting changes related to COVID-19. We sought to assess serial TTE changes in patients recovered from COVID-19 compared to baseline, pre-COVID-19 exams, with a focus on left and right ventricular longitudinal strain.
METHODS:
In this retrospective review of serial TTEs in confirmed COVID-19 patients at Mayo Clinic sites, included patients had a TTE within 2 years prior to confirmed COVID-19 diagnosis and the first available outpatient TTE after diagnosis used as comparison. Patients with interval cardiac surgery, procedure, or device placement (n=9) were excluded. Biventricular strain was retrospectively performed on both echocardiograms.
RESULTS:
Of 259 individuals, age 60±16 years, 47% female, and 88% Caucasian, post-COVID-19 TTEs were performed a median of 55 days (IQR 37-92) following diagnosis. No clinically significant TTE changes were noted, though left ventricular ejection fraction (LVEF) was higher (58% vs 57%, p=0.049) and tricuspid annulus plane systolic excursion lower (20 vs 21mm, p=0.046) following COVID-19. Baseline LV global longitudinal strain (LV GLS) and right ventricular free wall strain (RV FWS) were normal (-19.6% and -25.8%, respectively) and similar following COVID-19 (-19.6% and -25.7%, p=0.07 and 0.77, respectively). In the 74 inpatients, no significant change from baseline was seen for LV GLS (-19.4% vs -19.1%, p=0.62), RV FWS (-25.5% vs -25.0%, p=0.69), or LVEF (57% vs 57%, p=0.71). A significant worsening in strain occurred in 27 patients, 16 (6.8%) of the 237 with LV GLS and 14 (6.0%) of the 235 with RV FWS. Ten (20%) patients reporting new symptoms following COVID-19 had worsened strain, compared to 5 (7%) with persistent/progressive symptoms and 11 (9%) with no new symptoms (p=0.04).
CONCLUSIONS:
While patients with new symptoms following COVID-19 were more likely to have a worsening in absolute strain values, no clinically significant change in TTE parameters was evident in most patients following COVID-19 regardless of symptom status.
Copyright © 2022. Published by Elsevier Inc.
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Abdominal aortic aneurysm in heart transplant recipients: new insights from a 30-year experience at a single center.
Ann Vasc Surg2022 Jun;():. doi: S0890-5096(22)00311-9.
Tchana-Sato Vincent, Koch Jean-Noël, Ancion Arnaud, Adelin Albert, Minga Lowampa Elie, Burelli Mara, Defraigne Jean-Olivier, Sakalihasan Natzi,
Abstract
OBJECTIVE:
The improvement in survival rates for heart transplant recipients (HTRs) has increased their risk of developing extracardiac diseases such as abdominal aortic aneurysms (AAAs). The purposes of this study were to evaluate the prevalence and to describe the clinical features and natural history of AAA in HTRs.
METHODS:
A retrospective review of all patients (375) who underwent heart transplantation (HT) at our center over a 32-year period (1983-2015) was carried out.
RESULTS:
We identified 20 patients (5.3%) with AAA. All but one patient were male (95%), and most of them (80%) had a history of ischemic heart disease (IHD) prior to transplantation. The mean age of the patients with AAA at transplant was 57.2±7.3 years (range: 42-62 years). Seven of the 20 patients with AAA already had an AAA (30 to 55 mm) prior to transplantation. The average aneurysm size at the time of diagnosis was 40.9±9.6 mm, and the average patient age at the time of diagnosis was 62.2±8.3 years. The mean linear expansion rate was 10.6±2.12 mm/y, and the exponential expansion rate was 0.220±0.040 year respectively. The median follow-up time was 5.4 years (range 0.1-27.4 years). The median survival was 143 months (95% confidence interval (CI) 65 to 180 months) for the 20 HTRs with AAA and 68.8 months (95% CI 46 to 88 months) for the other HTRs.
CONCLUSIONS:
The natural history of AAA in HTR is characterized by an increased expansion rate. Male HTR with end-stage IHD are particularly at risk and should be closely followed-up after HT.
Copyright © 2022 Elsevier Inc. All rights reserved.
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Assessment of drinking water safety in the Netherlands using nationwide exposure and mortality data.
Environ Int2022 Jun;166():107356. doi: S0160-4120(22)00283-5.
Houthuijs Danny, Breugelmans Oscar R P, Baken Kirsten A, Sjerps Rosa M A, Schipper Maarten, van der Aa Monique, van Wezel Annemarie P,
Abstract
BACKGROUND:
Although drinking water in the Netherlands is generally accepted as safe, public concern about health risks of long-term intake still exist.
OBJECTIVE:
The aim was to explore associations between drinking water quality for nitrate, water hardness, calcium and magnesium and causes-of-death as related to cardiovascular diseases amongst which coronary heart disease and colorectal cancer.
METHODS:
We used national administrative databases on cause-specific mortality, personal characteristics, residential history, social economic indicators, air quality and drinking water quality for parameters specified by the EU Drinking Water Directive. We put together a cohort of 6,998,623 persons who were at least 30 years old on January 1, 2008 and lived for at least five years on the same address. The average drinking water concentration over 2000-2010 at the production stations were used as exposure indicators. We applied age stratified Cox proportional hazards models.
RESULTS:
Magnesium was associated with a reduced risk for mortality due to coronary heart diseases: HR of 0.95 (95% CI: 0.90, 0.99) per 10 mg/L increase. For mortality due to cardiovascular diseases, a 100 mg/L increase in calcium was associated with a HR of 1.08 (95% CI: 1.03, 1.13) and an increase of 2.5 mmol/L of water hardness with a HR of 1.06 (95% CI: 1.01, 1.10). The results show an elevated risk for coronary heart disease mortality at calcium concentrations below 30 mg/L, but over the whole exposure range no exposure response relation was observed. For other combinations of drinking water quality parameters and cause-specific mortality studied, no statistical significant associations were identified.
CONCLUSION:
We identified in this explorative study a protective effect of magnesium for the risk of mortality to coronary heart disease. Also we found an increased risk of mortality due to cardiovascular disease associated with the concentration of calcium and the water hardness in drinking water.
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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Identifying peripheral arterial diseases or flow limitations of the lower limb: Important aspects for cardiovascular screening for referral in physiotherapy.
Musculoskelet Sci Pract2022 Jun;61():102611. doi: S2468-7812(22)00111-4.
Feller Daniel, Giudice Andrea, Faletra Agostino, Salomon Mattia, Galeno Erasmo, Rossettini Giacomo, Brindisino Fabrizio, Maselli Filippo, Hutting Nathan, Mourad Firas,
Abstract
Many conditions could potentially cause pain in the lower limbs. One of these is peripheral arterial disease (PAD). PAD is often a real challenge to be recognized for clinicians due to symptoms that commonly mimic musculoskeletal conditions. PAD is defined as a total or partial blockage of the vessels that supply blood from the heart to the periphery. Its prevalence is around 7 percent in subjects between 55 and 59, reaching almost 25% in individuals between 95 and 99 years old. The most dominant symptom of PAD is lower limb pain. Also, PAD can produce other symptoms such as discoloration, altered skin temperature, and, when arterial blood flow is insufficient to meet the metabolic demands of resting muscle or tissue, focal areas of ischemia. In our view, physical therapists should be capable of triaging for PAD in a direct access setting. Therefore, in this Professional Issue, we present the main characteristics of PAD and the physiotherapy role in its management. A supplementary step-by-step guide will provide further resources for testing PAD.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Risk factors of clinically significant complications in transbronchial lung cryobiopsy: A prospective multi-center study.
Respir Med2022 Jun;200():106922. doi: S0954-6111(22)00187-1.
Mononen Minna, Saari Eeva, Hasala Hannele, Kettunen Hannu-Pekka, Suoranta Sanna, Nurmi Hanna, Randell Jukka, Laurikka Jari, Uibu Toomas, Koskela Heikki, Kaarteenaho Riitta, Purokivi Minna,
Abstract
BACKGROUND:
The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients.
METHODS:
Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ?90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications.
RESULTS:
The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03-1.65, p = 0.027) and young age (OR 7.96, CI 2.32-27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ?30 days before the TBLC (OR 3.65, CI 0.911-14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10-16.0, p = 0.036). Procedure associated mortality ?90 days was 1%.
CONCLUSION:
The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Anti-hyperglycemic, anti-hyperlipidemic, and anti-inflammatory effect of the drug Guggulutiktaka ghrita on high-fat diet-induced obese rats.
J Ayurveda Integr Med2022 Jun;13(3):100583. doi: S0975-9476(22)00042-0.
Sheik Samreen M, Bakthavatchalam Pugazhandhi, Shenoy Revathi P, Hadapad Basavaraj S, Nayak M Deepak, Biswas Monalisa, Bolar Suryakanth Varashree,
Abstract
BACKGROUND:
Ayurveda is a holistic system of medicine and describes a vast array of herbs and herbal mixtures that are been demonstrated to possess efficacy in research investigations. Guggulutikthaka gritha (GTG) is one such drug evaluated for its role in skin and bone diseases.
OBJECTIVE:
In the current study, the hypoglycemic, hypolipidemic, and anti-inflammatory effect of the drug GTG was studied with the scope to treat dyslipidemia and thereby reduce the risk of cardiovascular disease.
MATERIALS AND METHOD:
The animals (Wistar rats) were fed a high-fat diet and dyslipidemia was induced. The control group was provided with a normal chow diet and had free access to water. The treatment with the drug GTG was given for 21 days after confirming dyslipidemia. The blood glucose was measured immediately using a glucometer. The serum was analyzed for lipid profile and Vascular Cell Adhesion Molecule - 1(VCAM 1) by ELISA method before and after treatment. The histopathology of the heart and liver was also performed.
RESULTS:
The abnormal change in lipid profile, blood glucose, and inflammatory marker along with the accumulation of intracellular fats in the arteries of the heart and liver confirmed dyslipidemia. A significant reduction in serum lipid profile (p
CONCLUSION:
The study provides scientific validation on the drug GTG being effective in hyperglycemia, hyperlipidemia, and inflammation in dyslipidemia.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
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Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens.
Oral Oncol2022 Jun;132():105982. doi: S1368-8375(22)00271-8.
Alessandrini Lara, Ferrari Marco, Taboni Stefano, Sbaraglia Marta, Franz Leonardo, Saccardo Tommaso, Del Forno Bianca Maria, Agugiaro Francesca, Frigo Anna Chiara, Dei Tos Angelo Paolo, Marioni Gino,
Abstract
OBJECTIVES:
The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo-angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens.
METHODS:
TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases.
RESULTS:
TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox's model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p
CONCLUSIONS:
If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy.
Copyright © 2022 Elsevier Ltd. All rights reserved.
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Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.
Atherosclerosis2022 Jun;353():11-19. doi: S0021-9150(22)01316-8.
Alfaddagh Abdulhamied, Kapoor Karan, Dardari Zeina A, Bhatt Deepak L, Budoff Matthew J, Nasir Khurram, Miller Michael, Welty Francine K, Miedema Michael D, Shapiro Michael D, Tsai Michael Y, Blumenthal Roger S, Blaha Michael J,
Abstract
BACKGROUND AND AIMS:
High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events.
METHODS:
We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression.
RESULTS:
Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and log(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC?100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category.
CONCLUSIONS:
In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.
Copyright © 2022 Elsevier B.V. All rights reserved.
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Interleukin-35 ameliorates cardiovascular disease by suppressing inflammatory responses and regulating immune homeostasis.
Int Immunopharmacol2022 Jun;110():108938. doi: S1567-5769(22)00422-2.
Feng Jie, Wu Yanqing,
Abstract
The immune response is of great significance in the initiation and progression of a diversity of cardiovascular diseases involving pro-and anti-inflammatory cytokines. Interleukin-35 (IL-35), a cytokine of the interleukin-12 family, is a novel anti-inflammation and immunosuppressive cytokine, maintaining inflammatory suppression and regulating immune homeostasis. The role of IL-35 in cardiovascular diseases (CVDs) has aroused enthusiastic attention, a diversity of experimental or clinical evidence has indicated that IL-35 potentially has a pivot role in protecting against cardiovascular diseases, especially atherosclerosis and myocarditis. In this review, we initiate an overview of the relationship between Interleukin-35 and cardiovascular diseases, including atherosclerosis, acute coronary syndrome, pulmonary hypertension, abdominal aortic aneurysm, heart failure, myocardial ischemia-reperfusion, aortic dissection and myocarditis. Although the specific molecular mechanisms entailing the protective effects of IL-35 remain an unsolved issue, targeted therapies with IL-35 might provide a promising and effective solution to prevent and cure cardiovascular diseases.
Copyright © 2022 Elsevier B.V. All rights reserved.
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Machine learning decision tree algorithm role for predicting mortality in critically ill adult COVID-19 patients admitted to the ICU.
J Infect Public Health2022 Jun;15(7):826-834. doi: S1876-0341(22)00151-4.
Elhazmi Alyaa, Al-Omari Awad, Sallam Hend, Mufti Hani N, Rabie Ahmed A, Alshahrani Mohammed, Mady Ahmed, Alghamdi Adnan, Altalaq Ali, Azzam Mohamed H, Sindi Anees, Kharaba Ayman, Al-Aseri Zohair A, Almekhlafi Ghaleb A, Tashkandi Wail, Alajmi Saud A, Faqihi Fahad, Alharthy Abdulrahman, Al-Tawfiq Jaffar A, Melibari Rami Ghazi, Al-Hazzani Waleed, Arabi Yaseen M,
Abstract
BACKGROUND:
Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic.
METHODS:
This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses.
RESULTS:
There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio.
CONCLUSION:
DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.
JAMA2022 Jun;():. doi: 10.1001/jama.2022.9376.
Schlapbach Luregn J, Gibbons Kristen S, Horton Stephen B, Johnson Kerry, Long Debbie A, Buckley David H F, Erickson Simon, Festa Marino, d'Udekem Yves, Alphonso Nelson, Winlaw David S, Delzoppo Carmel, van Loon Kim, Jones Mark, Young Paul J, Butt Warwick, Schibler Andreas, ,
Abstract
Importance:
In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).
Objective:
To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.
Design, Setting, and Participants:
Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.
Interventions:
Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n?=?679) or standard care cardiopulmonary bypass without nitric oxide (n?=?685).
Main Outcomes and Measures:
The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.
Results:
Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P?=?.92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.
Conclusions and Relevance:
In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.
Trial Registration:
anzctr.org.au Identifier: ACTRN12617000821392.
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Treatment of Multisystem Inflammatory Syndrome in Children: Understanding Differences in Results of Comparative Effectiveness Studies.
ACR Open Rheumatol2022 Jun;():. doi: 10.1002/acr2.11478.
Melgar Michael, Seaby Eleanor G, McArdle Andrew J, Young Cameron C, Campbell Angela P, Murray Nancy L, Patel Manish M, Levin Michael, Randolph Adrienne G, Son Mary Beth F, ,
Abstract
OBJECTIVE:
Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS-C definitions and differing disease severity between cohorts underlay discrepant results.
METHODS:
The Overcoming COVID-19 Public Health Surveillance Registry (OC-19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS-C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC-19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts.
RESULTS:
Of 349 OC-19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC-19 patients had WHO-defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC-19 patients were more often admitted to intensive care (61.0% vs 44.8%, P?0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P?0.001) before immunomodulatory treatment.
CONCLUSION:
Greater illness severity and cardiovascular involvement in the OC-19 cohort compared with the BATS cohort, and not use of different MIS-C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS-C. Disease severity should be considered in future MIS-C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment.
© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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Molecular Mechanisms of Hepatic Dysfunction in Sickle Cell Disease: Lessons From The Townes Mouse Model.
Am J Physiol Cell Physiol2022 Jun;():. doi: 10.1152/ajpcell.00175.2022.
Pradhan-Sundd Tirthadipa, Kato Gregory J, Novelli Enrico M,
Abstract
Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects ~100,000 Americans and millions of people worldwide. Erythrocyte sickling, vaso-occlusion, sterile inflammation and hemolysis are the major pathophysiological pathways leading to liver injury in SCD. Although hepatic dysfunction affects up to 10-40% of SCD patients, therapeutic approaches to prevent liver injury in SCD are not known, and the molecular mechanisms promoting progressive liver injury in SCD remain poorly understood. Animal models have been beneficial in bridging the gap between preclinical and translational research in SCD. Recent advances in methodology have allowed the development of several humanized mouse models to address various aspects of SCD related liver diseases. This review provides an overview of current knowledge of the molecular mechanisms and potential therapeutic options of SCD associated liver dysfunction using the Townes mouse model.
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Neurohormonal Connections with Mitochondria in Cardiomyopathy and Other Diseases.
Am J Physiol Cell Physiol2022 Jun;():. doi: 10.1152/ajpcell.00167.2022.
Dorn Ii Gerald W,
Abstract
Neurohormonal signaling and mitochondrial dynamism are seemingly distinct processes that are almost ubiquitous among multicellular organisms. Both of these processes are regulated by GTPases, and disturbances in either can provoke disease. Here, inconspicuous pathophysiological connectivity between neurohormonal signaling and mitochondrial dynamism is reviewed in the context of cardiac and neurological syndromes. For both processes, greater understanding of basic mechanisms has evoked a reversal of conventional pathophysiological concepts. Thus, neurohormonal systems induced in, and previously thought to be critical for, cardiac functioning in heart failure are now pharmaceutically interrupted as modern standard of care. And, mitochondrial abnormalities in neuropathies that were originally attributed to an imbalance between mitochondrial fusion and fission are increasingly recognized as an interruption of axonal mitochondrial transport. The data are presented in a historical context to provided insight into how scientific thought has evolved and to foster an appreciation for how seemingly different areas of investigation can converge. Finally, some theoretical notions are presented to explain how different molecular and functional defects can evoke tissue-specific disease.
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Prevalence and Vascular Distribution of Multiterritorial Atherosclerosis Among Community-Dwelling Adults in Southeast China.
JAMA Netw Open2022 Jun;5(6):e2218307. doi: 10.1001/jamanetworkopen.2022.18307.
Pan Yuesong, Jing Jing, Cai Xueli, Jin Zening, Wang Suying, Wang Yilong, Zeng Chunlai, Meng Xia, Ji Jiansong, Li Long, Lyu Lingchun, Zhang Zhe, Mei Lerong, Li Hao, Li Shan, Wei Tiemin, Wang Yongjun,
Abstract
Importance:
Data are limited on the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in community populations.
Objective:
To investigate the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in older, community-dwelling populations in China.
Design, Setting, and Participants:
This cross-sectional study was based on the baseline survey from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study, a population-based prospective cohort study that enrolled community-dwelling adults aged 50 to 75 years based on cluster sampling from 6 villages and 4 living communities of Lishui city in southeast China. Data were collected from May 2017 to September 2019 and analyzed from September to November 2021.
Main Outcomes and Measures:
Atherosclerotic plaque and stenosis at baseline were assessed in multiple vascular territories. Brain vessel wall magnetic resonance imaging (MRI) for intracranial and extracranial arteries; computed tomography angiography (CTA) for coronary, subclavian, aorta, renal, and iliofemoral arteries; and ankle-brachial index for peripheral arteries were performed at baseline survey. The extent of atherosclerosis was assessed according to the number of these 8 vascular sites affected, and polyvascular lesions were defined as at least 2 affected sites.
Results:
A total of 3433 of 4202 invited individuals consented to participate in the study. After excluding 366 participants with contraindications for MRI or CTA scanning, with life expectancies of 4 years of fewer, or with mental disease, a total of 3067 community-dwelling adults were enrolled. The mean (SD) age was 61.2 (6.7) years; 1640 (53.5%) were women, and 74 (2.4%) had prevalent ASCVD. Most participants (2870 [93.6%]) had atherosclerotic plaques in at least 1 vascular territory. Atherosclerotic plaques were mostly detected in the aorta (2419 [79.6%]) and iliofemoral arteries (2312 [75.8%]), followed by subclavian (1500 [49.8%]), coronary (1366 [44.9%]), extracranial (1110 [36.4%]), renal (873 [28.7%]), and intracranial (542 [17.7%]) arteries. A substantial proportion of participants (1180 [38.5%]) had arterial stenosis of 50% or greater, predominantly affecting the coronary (542 [17.8%]) and iliofemoral (527 [17.3%]) arteries. Polyvascular atherosclerotic plaque was observed in 2541 participants (82.8%), with 1436 (46.8%) with plaque affecting 4 or more vascular territories, and polyvascular stenosis was observed in 412 patients (13.4%).
Conclusions and Relevance:
In this study, atherosclerotic plaque was highly prevalent in the older community population in China, and a substantial proportion of individuals reach stenosis of 50% or greater.
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LINC01013 Is a Determinant of Fibroblast Activation and Encodes a Novel Fibroblast-Activating Micropeptide.
J Cardiovasc Transl Res2022 Jun;():. doi: 10.1007/s12265-022-10288-z.
Quaife N M, Chothani S, Schulz J F, Lindberg E L, Vanezis K, Adami E, O'Fee K, Greiner J, Litvi?uková M, van Heesch S, Whiffin N, Hubner N, Schafer S, Rackham O, Cook S A, Barton P J R,
Abstract
Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGF?1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGF?1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGF?1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGF?1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation.
© 2022. The Author(s).
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Titin-related Cardiomyopathy: Is it a Distinct Disease?
Curr Cardiol Rep2022 Jun;():. doi: 10.1007/s11886-022-01726-0.
Santiago Celine F, Huttner Inken G, Fatkin Diane,
Abstract
PURPOSE OF REVIEW:
Truncating TTN variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM), but the underlying mechanisms are incompletely understood and effective therapeutic strategies are lacking. Here we review recent data that shed new light on the functional consequences of TTNtv and how these effects may vary with mutation location.
RECENT FINDINGS:
Whether TTNtv act by haploinsufficiency or dominant negative effects has been hotly debated. New evidence now implicates both mechanisms in TTNtv-related DCM, showing reduced titin content and persistent truncated titin that may be incorporated into protein aggregates. The extent to which aggregate formation and protein quality control defects differ with TTNtv location and contribute to contractile dysfunction is unresolved. TTNtv-associated DCM has a complex etiology that involves varying combinations of wild-type titin deficiency and dominant negative effects of truncated mutant titin. Therapeutic strategies to improve protein handling may be beneficial in some cases.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Thromboembolic complications of recreational nitrous oxide (ab)use: a systematic review.
J Thromb Thrombolysis2022 Jun;():. doi: 10.1007/s11239-022-02673-x.
Oulkadi Sanad, Peters Benjamin, Vliegen Anne-Sophie,
Abstract
The recreatinal use of nitrous oxide has become more common in recent years, especially in adolescents and young adults. It has been mainly associated with medical conditions like megaloblastic anemia and (myelo)neuropathy. We report on the thromboembolic complications, a less known side effect, associated with recreational inhalation of nitrous oxide. An extensive literature search was performed for publications reporting on the thromboembolic complications associated with recreational nitrous oxide abuse. Data about sex, age, location of thrombosis, laboratory findings, therapy and outcome were collected. A total of 13 case reports or case series were identified comprising a total of 14 patients. The reported thromboembolic side effects included deep venous thrombosis, pulmonary embolism, mesenterial-, portal and splenic vein thrombosis, cerebral sinus thrombosis, cortical vein thrombosis, stroke, acute myocardial infarction and peripheral artery thromboembolism. These side effects are possibly mediated by the interaction of nitrous oxide with vitamin B12, a cofactor of the methionine synthase complex, which eventually results in elevation of plasma levels of homocysteine. Despite being a known risk factor for cardiovascular disease, the exact pathophysiological mechanism remains unclear. Cessation of nitrous oxide inhalation is necessary to prevent recurrent thrombosis. Nitrous oxide abuse may thus result in a wide spectrum of thromboembolic complications. One should be aware of this etiology, especially in a young person with no obvious risk factors for cardiovascular disease. Spreading awareness is important to inform people about the potentially serious side effects associated with nitrous oxide inhalation.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Protective Effect of Cardiomyocyte-Specific Prolyl-4-Hydroxylase 2 Inhibition on Ischemic Injury in a Mouse MI Model.
J Am Coll Surg2022 Apr;():. doi: 10.1097/XCS.0000000000000241.
Pradeep Seetur R, Lim Sue Ting, Thirunavukkarasu Mahesh, Joshi Mandip, Cernuda Bryan, Palesty J Alexander, Maulik Nilanjana,
Abstract
BACKGROUND:
Our earlier studies showed that inhibiting prolyl-4-hydroxylase enzymes (PHD-1 and PHD-3) improves angiogenesis, heart function, and limb perfusion in mouse models via stabilizing hypoxia-inducible transcription factor-alpha (HIF-1?). The present study explored the effects of the prolyl-4-hydroxylase enzyme, PHD-2, on ischemic heart failure using cardiac-specific PHD-2 gene knockout (KO) mice (PHD2-/-).
STUDY DESIGN:
Adult wild-type (WT) and PHD2-/- mice, 8-12 weeks old, were subjected to myocardial infarction (MI) by irreversibly ligating the left anterior descending (LAD) coronary artery. All sham group mice underwent surgery without LAD ligation. Animals were divided into four groups 1) Wild-type Sham (WTS); Wild-Type myocardial infarction (WTMI); 3) PHD2KO Sham (PHD2-/-S); 4) PHD2KO myocardial infarction (PHD2-/-MI). Left ventricular tissue samples collected at various time points following surgery were used for microRNA expression profiling, Western blotting, immunohistochemical, and echocardiographic analysis.
RESULTS:
Volcano plot analysis revealed 19 differentially expressed miRNAs in the PHD2-/-MI compared to the WTMI group. Target analysis using Ingenuity Pathway Analysis showed several differentially regulated miRNAs targeting key signaling pathways such as Akt, VEGF, Ang-1, PTEN, apoptosis, and hypoxia pathways. Compared to the WTMI group, Western blot analysis showed increased HIF-1?, VEGF, phospho-AKT, and ?-catenin expression and reduced Bax expression for the PHD2-/-MI group post-MI. Echocardiographic analysis showed preserved heart functions, and picrosirius red staining revealed decreased fibrosis in PHD2-/-MI compared to the WTMI group.
CONCLUSION:
PHD2 inhibition showed preserved heart function, enhanced angiogenic factor expression, and decreased apoptotic markers after MI. Overall, PHD2 gene inhibition is a promising candidate for managing cardiovascular diseases.
Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.
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