Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

Clinical Outcomes with Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Systematic Review and Proportional Meta-analysis.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory condition that can present with heart failure (HF). Cardiac resynchronization therapy (CRT) is known to improve clinical outcomes for patients with left bundle branch block in the general HF population. However, data about the outcomes of CRT in CS is limited. METHODS: A systematic literature search was conducted using PubMed/Medline, Embase, and the Cochrane Library from inception to February 2024 to identify studies that reported clinical outcomes following the use of CRT in patients with CS. Data for outcomes was extracted, pooled, and analyzed. OpenMetaAnalyst was used for pooling untransformed proportions along with the corresponding 95% confidence intervals (CIs). RESULTS: Five studies with a total of 176 CS patients who received CRT were included. The pooled incidence for all-cause mortality was 7.6% (95% CI: -3% to 18%), for HF-related hospitalizations 23.2% (95% CI: 2% to 43%), and for major adverse cerebral and cardiovascular events 27% (95% CI: 8% to 45%) after a mean follow-up of 60.1 (±48.7) months. The pooled left ventricular ejection fraction (LVEF) was 34.28% (95% CI: 29.88% to 38.68%) demonstrating an improvement of 3.75% in LVEF from baseline LVEF of 30.58% (95% CI: 24.68% to 36.48%). The mean New York Heart Association (NYHA) functional class was 2.16 (95% CI: 1.47 to 2.84) after CRT as compared to the baseline mean NYHA of 2.58 (95% CI: 2.29 to 2.86). CONCLUSION: Although improvements were observed in LVEF and mean NYHA, mortality was high in CS patients with CRT.

Optical coherence tomography-guided vs. intravascular ultrasound-guided percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

Background: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are superior to coronary angiography for guiding percutaneous coronary intervention (PCI). However, whether one technique is superior to the other is inconclusive. Methods: We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to November 2023 for randomized controlled trials (RCTs) comparing OCT and IVUS in patients undergoing PCI. RevMan 5.4 was used to pool outcomes with risk ratio (RR) as the effect measure. Results: Six RCTs (4,402 patients) were included in this meta-analysis. There was no significant difference between the OCT- and IVUS-guided PCI groups in the risk of major adverse cardiovascular events (RR 0.87, 95% CI: 0.65, 1.16; I2 = 0%) and cardiac mortality (RR 0.73, 95% CI: 0.24, 2.21; I2 = 0%). The results were consistent across the subgroups of the presence or absence of left main disease (P interaction >0.1). There were no significant differences between OCT and IVUS in the risk of target lesion revascularization (RR 0.78, 95% CI: 0.47, 1.30; I2 = 0%), target vessel revascularization (RR 1.06, 95% CI: 0.69, 1.62; I2 = 0%), target-vessel myocardial infarction (RR 0.79, 95% CI: 0.40, 1.53; I2 = 0%), stent thrombosis (RR 0.59, 95% CI: 0.12, 2.97; I2 = 0%), and all-cause mortality (RR 1.01, 95% CI: 0.53, 1.90; I2 = 0%). Conclusions: Our meta-analysis demonstrated similar clinical outcomes in OCT- and IVUS-guided PCI. New large-scale multicenter RCTs with long-term follow-up are required to confirm or refute our findings and provide more reliable results. Systematic Review Registration: PROSPERO, identifier, CRD42023486933.

Characteristics and clinical outcomes of patients with sarcoidosis admitted for ST-elevation myocardial infarction in the United States: a propensity matched analysis from the National Inpatient Sample.

Introduction: Sarcoidosis is a systemic inflammatory disorder characterised by non-caseating granulomas. Cardiac sarcoidosis (CS) normally causes conduction abnormalities, ventricular arrhythmias, and heart failure. Little is known about the characteristics and impact of sarcoidosis in patients admitted with ST-elevation myocardial infarction (STEMI). This study aims to fill this void. Material and methods: Utilising the National Inpatient Sample (NIS) database (2016-2020), individuals with STEMI were identified and categorised based on sarcoidosis presence whilst adjusting for confounders via logistic regression models. Results: Among 851,290 STEMI patients, 1215 had sarcoidosis. Before propensity matching, sarcoidosis patients were notably different in demographics and comorbidities compared to non-sarcoidosis patients. After propensity score matching (PSM), sarcoidosis patients were found to have a higher incidence of supraventricular tachycardia (SVT) (2.5% vs. 1.3%, p = 0.024) and acute kidney injury (AKI) (23.3% vs. 20.8%, aOR = 1.269, 95% CI: 1.02-1.58, p = 0.033) but a lower incidence of undergoing coronary artery bypass graft (CABG) (5.5% vs. 8.5%, aOR = 0.663; 95% CI: 0.472-0.931, p = 0.018), while no significant disparities were noted in PCI, cardiogenic shock, mortality, or mean length of stay (LOS). Conclusions: Using propensity-matched large real-world data of STEMI patients, sarcoidosis was associated with fewer cases of CABG and a greater incidence of AKI and SVT compared to non-sarcoidosis patients.

Trends in admissions for COVID-19 in the United States between April 2020 and December 2021 and cardiovascular events.

Introduction: Coronavirus disease 2019 (COVID-19) can lead to cardiovascular complications. We aimed to understand the trends in admission for COVID-19 and the incidence of various cardiovascular events. Material and methods: The 2020 and 2021 National Inpatient Sample (NIS) was studied for cases of COVID-19 between April 2020 and December 2021 in the United States. Linear-by-linear association helped us understand the trends of various events. Results: The number of cases of COVID-19 was highest in January 2021 (261,469 patients). The incidence of acute pulmonary embolism rose from 2.08% in April 2020 to 4.82% in November 2021, while deep vein thrombosis cases rose from 1.74% in April 2020 to 2.63% in December 2021. The incidence of cardiac arrest varied, with a maximum of 3.00% in August 2021. Similarly, acute ischemic stroke cases experienced their highest incidence in January 2021 (0.91%). The incidence of myocarditis was highest in April and May 2020 (0.42% each). Peak takotsubo cases were seen between October and December 2021. The highest overall all-cause mortality among COVID-19 cases was seen in April 2020 (16.74%). Conclusions: Throughout the 21 months of our analysis, various trends in COVID-19 cases and incidence of cardiac events were noticed. This could relate to the different variants of COVID-19, their direct and indirect impact on coagulation pathways and the myocardial tissues, and the protective roles of the vaccines.

The role of infliximab in treating refractory cardiac sarcoidosis. Case series and systematic review of literature.

Cardiac sarcoidosis is associated with significant morbidity and mortality. Immunosuppressive treatment focuses on suppressing myocardial inflammation, which can lead to major adverse events especially when progressing to fibrosis. Conventional management usually includes steroids and steroid sparing agents such as methotrexate and azathioprine. Tumour necrosis factor alpha inhibitors are often reserved for those with a worsening clinical status and/or evidence of persistent inflammatory activity despite conventional therapy. Refractory cardiac sarcoidosis (CS) can be defined as the persistence or progression of active disease, evidenced either by lack of clinical response or persistence or progression of imaging abnormalities, despite being on conventional therapy. In the United Kingdom, tumour necrosis factor alpha inhibitors are currently not licensed for cardiac sarcoidosis as there are no randomised controlled trials to assess the efficacy of infliximab in this patient cohort. In this study, we present the outcomes of six patients treated with infliximab for refractory cardiac sarcoidosis at Royal Brompton Hospital and performed a systematic review of the existing literature on use of infliximab in cardiac sarcoidosis. We searched the Cochrane Library, OVID Medline, OVID Embase, Web of Science and Pubmed to identify 7 full-text studies assessing the role of infliximab in the management of cardiac sarcoidosis. Infliximab was found to play a vital role in stabilising refractory cardiac sarcoidosis by stemming clinical deterioration, arrythmia burden and even reducing steroids requirements. Further prospective trial data is necessary to validate these findings.

A Radiomic Approach for Evaluating Intra-Subgroup Heterogeneity in SHH and Group 4 Pediatric Medulloblastoma: A Preliminary Multi-Institutional Study.

Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for their intermediate prognosis, studies have reported wide disparities in patient outcomes within these subgroups. This study aims to create a radiomic prognostic signature, medulloblastoma radiomics risk (mRRisk), to identify the risk levels within the SHH and Group 4 subgroups, individually, for reliable risk stratification. Our hypothesis is that this signature can comprehensively capture tumor characteristics that enable the accurate identification of the risk level. In total, 70 MB studies (48 Group 4, and 22 SHH) were retrospectively curated from three institutions. For each subgroup, 232 hand-crafted features that capture the entropy, surface changes, and contour characteristics of the tumor were extracted. Features were concatenated and fed into regression models for risk stratification. Contrasted with Chang stratification that did not yield any significant differences within subgroups, significant differences were observed between two risk groups in Group 4 (p = 0.04, Concordance Index (CI) = 0.82) on the cystic core and non-enhancing tumor, and SHH (p = 0.03, CI = 0.74) on the enhancing tumor. Our results indicate that radiomics may serve as a prognostic tool for refining MB risk stratification, towards improved patient care.

Comparison of prognosis in isolated versus systemic manifestations of cardiac sarcoidosis.

BACKGROUND: Isolated cardiac sarcoidosis (iCS) is a poorly understood and under-recognised entity. Previous research has postulated that those with iCS have worsened outcomes compared to those with other manifestations of the disease, however, there have been studies which both support and refute this hypothesis. PURPOSE OF REVIEW: This review will summarise the literature which focuses on differences in the epidemiology, imaging findings and patient outcome of those with isolated cardiac sarcoidosis (iCS) versus 'systemic' cardiac sarcoidosis (sCS) which is not isolated to the heart. SUMMARY: Variations in study design make accurate comparison between current papers challenging, and that the factors which indicate poor prognosis in patients with iCS is not yet fully understood. Current literature suggests those with iCS are more likely to be male, have higher numbers of abnormal uptake patterns on cardiac imaging, and may have poorer prognosis than sCS patients. Multi-centre, prospective studies analysing isolated cardiac sarcoidosis across geographical regions are needed to improve our understanding of this phenomenon and ultimately improve patient outcome.

Age-related disparities in complications among women with peripartum cardiomyopathy.

INTRODUCTION: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age. METHODS: Records from the 2016-2020 National Inpatient Sample were used for our study. The sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in in-hospital complications between the two groups using multivariable regression. RESULTS: The analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, of whom 57.3 % were in the 30-40 years cohort and 42.7 % in the 15-29 years group. The prevalence of cardiovascular risk factors such as smoking, obesity, hypertension, diabetes and lipid disorder was higher among women aged 30-40 years (p < 0.01). These patients also demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95 % CI 1.038-1.767, p = 0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95 % CI 0.688-0.901, p < 0.01) as compared to those aged 15-29 years during their hospitalisation with PPCM. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95 % CI 0.976-1.182, p = 0.143), acute pulmonary oedema (aOR 1.147, 95 % CI 0.988-1.332, p = 0.071) or in-hospital mortality (aOR 0.978, 95 % CI 0.742-1.290, p = 0.877). CONCLUSION: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock.

TriClip G4: A game-changer for tricuspid valve regurgitation treatment.

Tricuspid valve regurgitation, or TR, is a difficult-to-manage condition. In addition to EVOQUE, percutaneous annuloplasty, and surgical repair, the TriClip G4 system has been added to the interventional therapeutic choices for TR. Recently, the Food and Drug Administration (FDA) approved the use of the TriClip G4 device to treat patients with symptomatic, severe TR who have received optimal medication therapy but are at intermediate or higher risk of surgery. This review attempts to offer a thorough examination of the procedural features, learning curves, results of the device and compares the TriClip G4 system to other interventional therapies for TR. TriClip G4 has shown to have promising results in pivotal clinical trials, be cost-effective, and improve the quality of life of patients. Furthermore, it has its unique advantages against other conventional techniques and devices.

The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Background: Dementia is a recognized complication of atrial fibrillation (AF). Oral anticoagulant (OAC) therapy can potentially be protective against this complication. Methods: A comprehensive search of MEDLINE and Embase for comparative observational studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. Studies that had patients with prior use of OAC or with a previous history of dementia were excluded. Results: A total of 22 studies were included in this review involving 617,204 participants. The pooled analysis revealed that OAC therapy, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), was associated with a reduced incidence of dementia in AF patients. Specifically, compared to non-OAC treatment, OACs demonstrated a significant reduction in dementia incidence (HR 0.68, 95 % CI [0.58, 0.80], p < 0.00001), with similar findings observed for DOACs (HR 0.69, 95 % CI [0.51, 0.94], p = 0.02) and VKAs (HR 0.73, 95 % CI [0.56, 0.95], p = 0.02). The comparison of DOAC vs VKA revealed that DOACs are associated with reduced risk of dementia (HR 0.87, 95 % CI [0.79, 0.96], p = 0.004). Conclusion: Our SR and meta-analysis showed that the use of OAC therapy is associated with a reduced risk of dementia in individuals with AF. However, our results are limited by the potential influence of confounding bias and significant heterogeneity in the analyses.

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration. Although the function of the outer mitochondrial CISD/NEET proteins, CISD1/mitoNEET and CISD2/NAF-1, has been defined in skeletal muscle cells, the role of the inner mitochondrial CISD protein, CISD3/MiNT, is currently unknown. Here, we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne muscular dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscles, as well as their mitochondria, and that CISD3 interacts with, and donates its [2Fe-2S] clusters to, complex I respiratory chain subunit NADH Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2). Using coevolutionary and structural computational tools, we model a CISD3-NDUFV2 complex with proximal coevolving residue interactions conducive of [2Fe-2S] cluster transfer reactions, placing the clusters of the two proteins 10 to 16 Å apart. Taken together, our findings reveal that CISD3/MiNT is important for supporting the biogenesis and function of complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact different muscle degeneration syndromes, aging, and related conditions.

Comparing outcomes of an 'early' versus 'late' diagnosis of cardiac sarcoidosis following a baseline presentation of high-grade atrioventricular block.

BACKGROUND: There is a paucity of evidence on impact of a delay in Cardiac Sarcoidosis (CS) diagnosis after high-grade atrioventricular-block (AVB) and this study aims to fill this void. METHODS: Consecutive CS patients (n = 77) with high grade AVB referred to one specialist hospital in London between February 2007 to February 2023 were retrospectively reviewed. The median time from AVB to diagnosing CS (112 days) was used to define the Early (n = 38) and Late (n = 39) cohorts. The primary endpoint was a composite of all-cause mortality, cardiac transplantation, ventricular arrhythmic events or heart failure hospitalisation. Secondary endpoints included difference in maintenance prednisolone dose, need for cardiac device upgrade and device complications. RESULTS: The mean age of the cohort was 54.4 (±10.6) years of whom 64 % were male and 81 % Caucasian. After a mean follow up of 54.9 (±45.3) months, the primary endpoint was reached by more patients from the Late cohort (16/39 vs. 6/38, p = 0.02; multivariable HR 6.9; 95 %CI 1.5-32.2, p = 0.01). Early Group were more likely to have received an Implantable Cardioverter Defibrillator or Cardiac Resynchronisation Therapy-defibrillator as index device after AVB (19/38 vs. 6/39; p < 0.01) and had fewer device upgrades (19/38 vs. 30/39, p = 0.01) and a trend towards fewer device complications (1 vs. 5, p = 0.20). The maintenance dose of prednisolone was significantly higher in Late Group [20.7(±9.7) mg vs. 15.3(±7.9) mg, p = 0.02]. CONCLUSION: A late diagnosis of CS was associated with more adverse events, a greater probability of needing a device upgrade and required higher maintenance steroid dose.

Characteristics and Outcomes of Hospitalized Patients with Heart Failure and Sarcoidosis: A Propensity-Matched Analysis of the Nationwide Readmissions Database 2010-2019.

BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010 to 2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, 9th and 10th Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs 1.4%, P < .0001), ventricular tachycardia (6.5% vs 1.3%, P < .0001), ventricular fibrillation (0.4% vs 0.1%, P < .0001) and atrial fibrillation (22.1% vs 7.5%, P < .0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, P < .0001), had higher length of hospital stay (5 vs 4 days, P < .0001), adjusted healthcare-associated costs ($9,667.0 vs $9,087.1, P < .0001) and mortality rates on readmission (5.1% vs 3.8%, P < .0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI, and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

Disparities and Outcomes in the First and Second Year of the Pandemic on Events of Acute Myocardial Infarction in Coronavirus Disease 2019 Patients.

Background and Objectives: Coronavirus disease 2019 (COVID-19) caused several cardiovascular complications, including acute myocardial infarction (AMI), in infected patients. This study aims to understand the overall trends of AMI among COVID-19 patients during the first two years of the pandemic and the disparities and outcomes between the first and second years. Materials and Methods: The retrospective analysis was conducted via the 2020 and 2021 National Inpatient Sample (NIS) database for hospitalizations between April 2020 and December 2021 being analyzed for adults with a primary diagnosis of COVID-19 who experienced events of AMI. A comparison of month-to-month events of AMI and mortality of AMI patients with concomitant COVID-19 was made alongside their respective patient characteristics. Results: Out of 2,541,992 COVID-19 hospitalized patients, 3.55% experienced AMI. The highest rate of AMI was in December 2021 (4.35%). No statistical differences in trends of AMI mortality were noted over the 21 months. AMI cases in 2021 had higher odds of undergoing PCI (aOR 1.627, p < 0.01). They experienced higher risks of acute kidney injury (aOR 1.078, p < 0.01), acute ischemic stroke (aOR 1.215, p < 0.01), cardiac arrest (aOR 1.106, p < 0.01), need for mechanical ventilation (aOR 1.133, p < 0.01), and all-cause mortality (aOR 1.032, 95% CI 1.001-1.064, p = 0.043). Conclusions: The incidence of AMI among COVID-19 patients fluctuated over the 21 months of this study, with a peak in December 2021. COVID-19 patients reporting AMI in 2021 experienced higher overall odds of multiple complications, which could relate to the exhaustive burden of the pandemic in 2021 on healthcare, the changing impact of the virus variants, and the hesitancy of infected patients to seek care.