Intravenous iron therapy for patients with iron deficiency and heart failure: a systematic review and meta-analysis of randomized controlled trials.

Introduction: Heart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue. Method: We assessed IV iron therapy's efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: Based on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable. Conclusions: IV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.

The Contemporary Use of Intracoronary Brachytherapy for In-Stent Restenosis: A Review.

In-stent restenosis (ISR) has been a major limitation in interventional cardiology and constitutes nearly 10 % of all percutaneous coronary interventions in the United States. Drug-eluting stent (DES) restenosis proves particularly difficult to manage and poses a high risk of recurrence and repeat intervention. Intra-coronary brachytherapy (IBT) has been traditionally viewed as a potential treatment modality for ISR. However, its use was hindered by procedural complexity, cost, and the advent of newer-generation DES. Recent data suggests promising results regarding IBT for the treatment of resistant DES-ISR. This review addresses the mechanism of action of IBT, procedural details, and associated risks and complications of its use. It will also highlight the available clinical evidence supporting the use of IBT and the future directions of its utilization in the treatment of ISR.

Pregnancy and Fetal Outcomes in Patients With Ehlers-Danlos Syndrome: A Nationally Representative Analysis.

Cardiovascular complications occur frequently in Ehlers-Danlos syndrome (EDS). Pregnancy outcomes, however, are not well established in patients with EDS. We conducted a population-based, retrospective, cohort study using the national inpatient sample to compare pregnancy and fetal outcomes in patients with and without EDS, delivering between 2016 and 2019. Regression analysis was performed and adjusted for maternal age and race to compare both groups. Of the total 5,887,050 births in our cohort, 1016 were to patients with EDS. The EDS cohort was more likely to be older, white and have multiple comorbidities, such as smoking, mitral valve prolapse, and chronic hypertension. When we adjusted for age and race, patients with EDS were more likely than those without EDS to require Cesarean-section, develop postpartum hemorrhage, experience intrauterine growth restriction, and deliver preterm. In this study, patients with EDS experienced higher rates of maternal complications, however, aortic aneurysmal rupture was not among them.

Efficacy and Safety of the Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Nonvalvular Atrial Fibrillation and Cancer: A Systematic Review and Network Meta-analysis.

Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in cancer patients with AF. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of NOACs compared with warfarin. A search through Pubmed/MEDLINE, Embase, and Cochrane library was done from the databases inception to March 2022. Studies that compared NOACs to warfarin in the setting of AF and cancer were included. The primary outcomes were the incidence of major bleeding and ischemic stroke/systemic embolism (SE). Secondary outcomes were major adverse cardiovascular event (MACE), intracranial bleeding, and Major gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CI) were used to report the outcomes. A total of 11 studies were included. We found that NOACs were associated with a lower incidence of major bleeding and combined ischemic stroke/SE in patients with AF and cancer compared with warfarin (RR 0.57; 95% CI 0.44-0.75, P < 0.0001 and RR 0.59; 95% CI 0.47-0.75, P < 0.0001, respectively). Also, there was lower incidence of Intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin (P < 0.0001). Network analyses revealed that apixaban and dabigatran were associated with reduction of major bleeding compared with warfarin. Among patients who diagnosed with AF and cancer, NOACs were associated with lower incidence of major bleeding ischemic stroke/SE compared with warfarin. Furthermore, NOACs were associated with lower gastrointestinal and intracranial bleeding.

AngioVac for Vegetation Debulking in Right-sided Infective Endocarditis: A Systematic Review and Meta-Analysis.

To investigate the utility of AngioVac-assisted vegetation debulking (AVD) in right sided infective endocarditis (RSIE). AngioVac is a vacuum-based device that was approved in 2014 for the percutaneous removal of undesirable materials from the intravascular system. Although there are multiple reports on the use of the AngioVac device to aspirate right-sided heart chamber thrombi, data on its use to treat RSIE is limited. We performed a comprehensive literature search for studies that evaluated the utility of AVD. The primary outcomes of our study were the procedural success, defined as the ability of AngioVac to produce residual vegetation size <50% (RVS<50%) without serious procedural complications, and the clinical success, defined as composite of RVS<50%, in-hospital survival, absence of recurrent bacteremia, and valve function not requiring further intervention. The secondary outcomes included the individual components of the primary outcomes and average length of hospital stay. The pooled means and proportions of our data were analyzed using random effects model, generic inverse variance method, and represented with 95% confidence intervals (CIs). A total of 44 studies, including 301 patients (mean age: 44.6 ± 18.2 years, 71.6% males) were included. Procedural success was achieved in 89.2% of patients (95% CI:82.3%-93.6%, I2 = 0%). Clinical success was achieved in 79.1% of patients (95% CI:67.9%-87.2%, I2 = 15%). Overall survival rate was 89.7% (95% CI:83.1%-93.9%%, I2 = 9%). Our meta-analysis demonstrates that AVD is a promising therapeutic option for RSIE offering a high success rate with an acceptable complication rate across a wide range of patients.

A systematic review and meta-analysis of the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction. METHODS: This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction. RESULTS: Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I2=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I2=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I2=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I2=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I2=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I2=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I2=87%) compared with transthyretin negative group. CONCLUSION: Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.

P2Y12 Inhibitors versus Aspirin Monotherapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-analysis.

Patients with established atherosclerotic cardiovascular disease (ASCVD) need long-term antiplatelet therapy to decrease the risk of future ASCVD events. We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through September 2021) for randomized controlled trials (RCTs) evaluating P2Y12 inhibitors vs aspirin for secondary prevention of ASCVD events. Seven RCTs including a total of 56,982 patients were included in this analysis. The median follow-up duration was 22.8 (IQR 12) months. When P2Y12 inhibitors were compared with aspirin as long-term antiplatelet therapy for secondary prevention of ASCVD events, there was a significant decrease in the risk of myocardial infarction [RR: 0.83; 95% CI: 0.72-0.94], and stroke [RR: 0.90; 95% CI: 0.83-0.99]. However, there was no significant difference in all-cause mortality [RR: 1.02; 95% CI: 0.92-1.12], or cardiovascular mortality [RR: 0.95; 95% CI: 0.83-1.08] between P2Y12 inhibitors and aspirin users. Additionally, there was no significant difference in major bleeding events [RR: 0.88; 95% CI: 0.74-1.04], or all bleeding events [RR: 1.09; 95% CI: 0.90-1.33] between P2Y12 inhibitors and aspirin groups. Use of P2Y12 inhibitor monotherapy is associated with lower rates of myocardial infarction and stroke in ASCVD patients without any significant difference in mortality, or bleeding compared to aspirin monotherapy.

Ischemic and Bleeding Outcomes of Potent P2Y12 Inhibitor Antiplatelet Agents Versus Clopidogrel in Elderly Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials.

BACKGROUND: The role of P2Y12 inhibition in acute coronary syndrome (ACS) has been well described in literature. However, the agent of choice is less clear among elderly patients (>65 years) who are at increased risk of bleeding. This meta-analysis was designed to investigate the efficacy and safety of potent P2Y12 inhibitors vs. clopidogrel in this population. METHODS AND RESULTS: PubMed, Cochrane Central Register of Clinical Trials, EMBASE, and ClinicalTrial.gov (inception through February 25, 2021) were searched for randomized studies comparing potent oral P2Y12 inhibitors to clopidogrel in elderly population presenting with ACS. Study endpoints included major adverse cardiac events (MACE), major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed and p<0.05 was considered significant. Eight randomized studies with a total 10,081 patients were included in the final analysis. At mean follow up of 26 months, there were no significant differences between potent oral P2Y12 inhibitors and clopidogrel in MACE (HR 0.97, 95% CI [0.82-1.15]; p=0.73), all-cause mortality (HR 0.91, 95% CI [0.75-1.10]; p=1.00), MI (HR 0.95, 95% CI [0.78-1.17]; p=0.64), and stroke (HR 1.24, 95% CI [0.82-1.86]; p=0.31). However, potent oral P2Y12 inhibitors were associated with a reduction in cardiovascular mortality (HR 0.82, 95% CI [0.68-0.98]; p=0.03), and an increase in major bleeding events (HR 1.32, 95% CI [1.09-1.59]; p<0.01). CONCLUSION: In comparison with clopidogrel, the use of potent oral P2Y12 inhibitors in elderly patients with ACS, is associated with a reduction in the risk of cardiovascular mortality with increased risk of bleeding events and no significant change in MACE outcomes.

Pregnancy-Associated Myocardial Infarction: A Review of Current Practices and Guidelines.

PURPOSE OF REVIEW: Pregnancy-associated myocardial infarction is a principal cause of cardiovascular disease with a steadily rising incidence of 4.98 AMI events/100,000 deliveries over the last four decades in the USA. It is also linked with significant maternal and fetal morbidity and mortality, with maternal case fatality rate ranging from 5.1 to 37%. The management of acute myocardial infarction can be challenging in pregnant patients since treatment modalities and medication use are limited by their safety during pregnancy. RECENT FINDINGS: Limited guidelines exist regarding the management of pregnancy-associated myocardial infarction. Routinely used medications in myocardial infarction including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and statin therapy are contraindicated during pregnancy. Aspirin use is considered safe in pregnant women, but dual antiplatelet therapy and therapeutic anticoagulation can be associated with increased risk of maternal and fetal complications, and should only be used after a comprehensive benefit-to-risk assessment. The standard approach to revascularization requires additional caution in pregnant women. Percutaneous coronary intervention is generally considered safe but can be associated with high failure rates and poor outcomes depending on the etiology. Fibrinolytic therapy may have significant sequelae in pregnant patients, and hemodynamic management during surgery is complex and adds risk during pregnancy. Understanding the risks and benefits of the different treatment modalities available and their utility depending on the underlying etiology, encompassed with a multidisciplinary team approach, is vital to improve outcomes and minimize maternal and fetal complications.

An Unusual Association between Neurofibromatosis Type 1 and Diffuse B Cell Lymphoma.

Neurofibromatosis type 1 (NF-1) is known to be associated with increased risk of malignancy by at least fourfold. Malignant lymphomas are rare in adults with NF-1. Hereby, we present a 75-year-old male with NF-1 complaining of weakness, nausea, and vomiting associated with abdominal pain. Three months prior to presentation, he had suffered a motor vehicle accident (MVA) resulting in multiple rib fractures that was seen in chest X-ray. For the following three months, he had intermittent chest pain, but it was attributed to the recent rib fracture. During this admission, the severity of chest pain worsened and the associated vomiting inclined further investigation; including CT imaging and bone biopsy, it was revealed to be a rare case of diffuse B cell lymphoma in a patient with NF-1. However, we believe the recent MVA caused an anchoring bias in making a prompt diagnosis. In addition, the appearance of the neurofibroma, resulted in suboptimal physical examination, and hence, there was a delay in reaching the diagnosis. We will discuss here the presentation of this case, to highlight the rare association and to increase awareness of when encountering a challenging diagnosis.

Valve-in-valve transcatheter aortic valve replacement versus redo surgical valve replacement for degenerated bioprosthetic aortic valve: An updated meta-analysis comparing midterm outcomes.

BACKGROUND: Redo surgical aortic valve replacement (redo SAVR) and valve-in-valve transcatheter aortic valve replacement (ViV TAVR) are the two treatment strategies available for patients with severe symptomatic bioprosthetic aortic valve dysfunction. Herein, we performed a systematic review and meta-analysis comparing both early and mid-term outcomes of ViV TAVR versus redo SAVR in patients with bioprosthetic aortic valve disease. METHODS: PubMed, Cochrane reviews, and Google scholar electronic databases were searched and studies comparing ViV TAVR versus redo SAVR were included. The primary outcome of interest was mid-term (1-5 years) and 1-year all-cause mortality. Secondary outcomes included were 30-day all-cause mortality, myocardial infarction, pacemaker implantation, stroke, acute kidney injury, major or life-threatening bleeding, and postprocedural aortic valve gradients. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CIs) were calculated for all outcomes using the DerSimonian-Laird random-effects model. RESULTS: Nine observational studies with a total of 2,891 individuals and mean follow-up of 26 months met the inclusion criteria. There is no significant difference in mid-term and 1-year mortality between ViV-TAVR and redo SAVR groups with RR of 1.15 (95% CI 0.99-1.32; p = .06) and 1.06 (95% CI 0.69-1.61; p = .8). 30-day mortality rate was significantly lower in ViV-TAVR group with RR of 0.65 (95% CI 0.45-0.93; p = .02). ViV-TAVR group had lower 30-day bleeding, length of stay, and higher postoperative gradients. CONCLUSION: Our study demonstrates a lower 30-day mortality and similar 1-year and mid-term mortality for ViV TAVR compared to redo SAVR despite a higher baseline risk. Given these findings and the ongoing advances in the transcatheter therapeutics, VIV TAVR should be preferred over redo SAVR particularly in those at intermediate-high surgical risk.

Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The nucleotide analogue prodrug remdesivir was among the first antiviral therapies to be tested in randomized controlled trials (RCTs) for COVID-19. We performed a meta-analysis to understand efficacy and safety. METHODS: We searched PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov databases (from January 1, 2020 to November 5, 2020). We included RCTs comparing the efficacy and safety of remdesivir to control/placebo in COVID-19. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. RESULTS: A total of 4 RCTs with 7334 patients with COVID-19 were included. At a follow-up of 28-29 days from randomization, very low certainty evidence showed that use of remdesivir compared with control group (placebo and/or standard of care) was not associated with a significant decrease in time to clinical improvement (standardized mean difference -0.80 day; [CI, -2.12, 0.53]). However, moderate certainty of evidence showed that remdesivir was associated with higher rates of recovered patients (risk difference [RD] 0.07 [0.05, 0.08]) and discharged patients (RD 0.07 [0.03, 0.11]) and lower rates of developing serious adverse events (RD -0.05 [-0.10, -0.01]) compared with control. Moderate and very low certainty of evidence showed there was no significant difference in deaths at 28-29 days follow-up (RD -0.01 [-0.03, 0.01]) and developing any adverse events (RD 0.01 [-0.17, 0.19]) between both groups, respectively. CONCLUSION: Patients given remdesivir are more likely to demonstrate recovery and were associated with higher rates of hospital discharge, but not with significant reduction in mean time to clinical improvement or mortality.

E-Cigarette or Vaping Product Use-Associated Lung Injury: A Severe Case That Responded to Corticosteroid Treatment.

Vaping is associated with an increased risk of lung injury; however, each case of vaping-associated lung injury leads to varying degrees of lung injury, and the response to therapy can be heterogeneous. Corticosteroid use has been suggested as a treatment for lung injuries associated with vaping. We report a case of e-cigarette or vaping product use-associated lung injury (EVALI) that resulted in acute hypoxic respiratory failure. A 20-year-old woman presented with complaints of sore throat, dry cough, shortness of breath, and pleuritic chest pain. The patient admitted to vaping regularly for the past three years. The patient was found to be severely hypoxemic with respiratory distress and was intubated shortly after her arrival at the emergency department. She was treated with a short course of corticosteroids with tapering of the dose based on her response with significant improvement, and she was extubated on the seventh day of her admission. EVALI is a syndrome associated with severe lung injury that results in acute respiratory failure that is clinically indistinguishable from acute respiratory distress syndrome, and it is largely a diagnosis of exclusion. The use of systemic corticosteroids in treating these patients should be considered after excluding an infectious etiology.

Incidental Diagnosis of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma: A Case Report.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, rapidly progressive, primary intestinal T-cell lymphoma. It is most commonly seen in the Asian and Hispanic populations and is usually not related to celiac disease, unlike type I enteropathy associated T-cell lymphoma. The most common site of occurrence is the small intestine. Patients usually present during the advanced stage of disease with clinical features of intestinal perforation or obstruction. The late clinical presentation and lack of targeted therapy are factors contributing to its poor prognosis. Here, we are presenting the case of a patient who initially came to the hospital for a urinary tract infection. As his abdominal CT scan showed abdominal wall thickening, he underwent further workup which revealed the diagnosis of MEITL.

Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke. METHODS: Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. RESULTS: We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke. CONCLUSIONS: Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

Hydralazine-induced antineutrophil cytoplasmic antibody-associated vasculitis with pulmonary-renal syndrome: a case report.

BACKGROUND: Hydralazine is a common vasodilator which has been used for the treatment of hypertension and heart failure. Hydralazine can induce antineutrophil cytoplasmic antibody-associated vasculitis due to its auto-immunogenic capability and one of the very rare presentations is pulmonary-renal syndrome. CASE PRESENTATION: We report a case of a 64-year-old African American woman, who presented to our emergency room with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, leg swelling, fatigue, loss of appetite, cough with clear sputum, and lightheadedness. On admission, she developed acute hypoxic respiratory failure requiring intubation and acute renal failure requiring hemodialysis. A serologic workup was positive for antineutrophil cytoplasmic antibody, antinuclear antibody, anti-histone, anti-cardiolipin IgM, and anti-double-stranded DNA antibodies. A renal biopsy was done due to persistent deterioration in kidney function and demonstrated classic crescentic (pauci-immune) glomerulonephritis. Hydralazine was empirically discontinued early in the admission and she was started on corticosteroids and cyclophosphamide following biopsy results. She was clinically stable but remained dependent on hemodialysis after discharge. CONCLUSION: Hydralazine-induced antineutrophil cytoplasmic antibody-associated vasculitis with pulmonary-renal syndrome is a rare occurrence. In the setting of hydralazine use, multiple positive antigens, and multisystem involvement, clinicians should consider this rare condition requiring prompt cessation of offending drug, early evaluation with biopsy, and contemplate empiric immunosuppressive therapy while biopsy confirmation is pending.