Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

ABSTRACT: Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.

Colchicine for Patients With Coronary Artery Disease: A Systematic Review and Meta-analysis.

ABSTRACT: Several randomized controlled trials have studied the role of colchicine, a potent anti-inflammatory drug, to prevent adverse cardiovascular events in patients with coronary artery disease (CAD). In this meta-analysis, we aimed to determine the role of colchicine in patients with CAD in clinical outcomes and mortality. We searched PubMed, PubMed Central, Scopus, and Embase for randomized controlled trials/experimental studies evaluating the role of colchicine in patients with CAD. After assessing the eligibility for inclusion, risk-of-bias assessment, and data extraction from the included studies, a narrative synthesis was conducted. Of 17 studies included for the qualitative analysis, 11 studies reported that inflammatory markers such as C-reactive protein and cytokines were reduced in the colchicine group, suggesting an anti-inflammatory role of colchicine in CAD. Quantitative analysis with pooling of data from 9 studies using a fixed-effect model showed 28% lower odds of acute myocardial infarction [odds ratio (OR) 0.72, 95% CI 0.59-0.86; n = 11,712], 52% lower occurrence of stroke (OR 0.48, 95% CI 0.30-0.76), and 37% reduction in odds of coronary revascularization procedure in the colchicine group (OR 0.63, 95% CI 0.52-0.76; n= 11,258). However, the odds of gastrointestinal adverse events were 50% higher in the colchicine group (OR 1.50, 95% CI 1.01-2.23; n = 12,214). In conclusion, colchicine is associated with a lower risk of acute myocardial infarction, stroke, and coronary revascularization. However, there is some increased risk of gastrointestinal adverse events with the use of colchicine.

Sodium-glucose cotransporter-2 Inhibitors in Heart Failure: An Updated Systematic Review and Meta-analysis of 13 Randomized Clinical Trials Including 14,618 Patients With Heart Failure.

ABSTRACT: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors showed benefit in patients with heart failure. In this updated meta-analysis, we evaluate the therapeutic efficacy and safety of SGLT-2 inhibitors in patients with heart failure. Different electronic databases were searched to find relevant articles. RevMan 5.4 was used for pooling data using a random/fixed-effects model, complemented by several sensitivity and subgroup analyses. A total of 13 randomized clinical trials including 14,618 patients with heart failure were included in analysis among 6797 studies screened. The overall mortality rate was 12.45% in the SGLT-2 group and 14.67% in the placebo group with 18% lower odds of overall mortality [odds ratio (OR), 0.82; confidence interval (CI), 0.75-0.91] in the SGLT-2 group. Odds of cardiovascular mortality was 18% lower (OR, 0.82; CI, 0.74-0.92) in the SGLT-2 group. The odds of hospitalization for heart failure (HHF) was 38% lower during the study period (OR, 0.62; CI, 0.56-0.68) in the SGLT-2 group. In addition, a benefit was seen for composite outcome HHF or mortality and considering subgrouping based on diabetes status, gender, and age groups. Although genital infection was significantly higher in the SGLT-2 group, the occurrence of severe adverse events, hypoglycemia, urinary tract infection, bone fracture, volume depletion, and other renal events did not differ between the 2 groups. Thus, SGLT-2 inhibitors improved cardiovascular outcomes among patients with heart failure with no significant difference in adverse events. Clinical benefit was comparable in diabetic and nondiabetic individuals, males and females, people in younger and older age groups with underlying heart failure, and HF with reduced ejection fraction.

Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis.

Background and Aim: Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF. Methods: The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Results: Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81). Conclusion: Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Patent foramen Ovale-related paradoxical embolism after noncardiac surgery.

Patent foramen ovale (PFO) is a remnant of the fetal circulation that remains in a significant portion of the adult population, predisposing to a higher risk of stroke. This risk is further elevated in the postoperative hypercoagulative period. Here we present a case where a patient underwent a total knee arthroplasty and presented with right-sided hemiparesis on post-operative day 2. Subsequently, the patient underwent percutaneous PFO closure with a 25-mm Amplatzer PFO Occluder (Abbott; Chicago, IL, USA). The patient has not had a stroke since the PFO closure. Recent randomized trials have demonstrated superiority of percutaneous PFO closure over standard-of-care medical therapy for secondary prevention of PFO-associated stroke. Since post-operative PFO-associated stroke is under-recognized in clinical practice, further large-cohort studies are needed to evaluate whether PFO screening and device closure would decrease post-operative stroke risk for noncardiac surgeries. Learning Objective: Patent foramen ovale (PFO) is a remnant of the fetal circulation commonly found in the adult population, which can increase the risk of stroke. Stroke is a complication of PFO, yet closure of this remnant only occurs on a specific case-by-case basis. Further research in this area is required to determine whether a larger population would benefit from PFO closure.

Direct oral anticoagulants (DOAC) versus vitamin K antagonist in left ventricular thrombus: An updated meta-analysis.

Background and Aims: Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta-analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT. Methods: Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all-cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio. Results: Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07-1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36-1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52-0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53-0.96) were also significantly lower in the DOAC group. Conclusion: DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance.

Efficacy and Safety of Pulsed Field Ablation in Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with high morbidity and mortality. AF treatment is guided by a patient-provider risk-benefit discussion regarding drug versus ablation or combination. Thermal ablation has a high rate of adverse events compared to pulsed field ablation (PFA). In this systematic review, we aimed to determine the safety and efficacy of PFA. METHODS: The electronic search for relevant articles in English was completed in PubMed, PubMed Central, Cochrane library, Scopus, and Embase databases till July 2022. The screening was completed via the use of Covidence software. The risk of bias assessment and data extraction from the included studies was performed, and the narrative synthesis was performed accordingly. RESULTS: A total of six studies were selected for review and 1897 patients receiving PFA were involved in these studies. Our review was focused on pulmonary vein isolation success, major adverse events, and arrhythmia recurrence. Successful pulmonary vein isolation (PVI) was completed in 100% of cases except in two studies. In one of them, six out of seven patients (86%) in the epicardial cohort had successful PVI. In the MANIFEST-PF survey, the acute PVI success rate was 99.9%. The major complications were rare and included pericardial tamponade, vascular complications requiring surgery, and stroke. The atrial arrhythmia recurrence was higher in the thermal group than in the PFA group (39% vs. 11%). CONCLUSIONS: The success rate of PVI by PFA is high, and major adverse events are low. PFA is found to decrease the recurrence of atrial arrhythmia compared to thermal ablation. Substantial randomized controlled trials (RCTs) are needed to validate the efficacy and safety of PFA over conventional methods.

Outcome of In-Hospital Cardiac Arrest among Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes following in-hospital cardiac arrest (IHCA) in patients with COVID-19 have been reported by several small single-institutional studies; however, there are no large studies contrasting COVID-19 IHCA with non-COVID-19 IHCA. The objective of this study was to compare the outcomes following IHCA between COVID-19 and non-COVID-19 patients. METHODS: We searched databases using predefined search terms and appropriate Boolean operators. All the relevant articles published till August 2022 were included in the analyses. The systematic review and meta-analysis were conducted as per Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An odds ratio with a 95% confidence interval (CI) was used to measure effects. RESULTS: Among 855 studies screened, 6 studies with 27,453 IHCA patients (63.84% male) with COVID-19 and 20,766 (59.7% male) without COVID-19 were included in the analysis. IHCA among patients with COVID-19 has lower odds of achieving return of spontaneous circulation (ROSC) (OR: 0.66, 95% CI: 0.62-0.70). Similarly, patients with COVID-19 have higher odds of 30-day mortality following IHCA (OR: 2.26, 95% CI: 2.08-2.45) and have 45% lower odds of cardiac arrest because of a shockable rhythm (OR: 0.55, 95% CI: 0.50-0.60) (9.59% vs. 16.39%). COVID-19 patients less commonly underwent targeted temperature management (TTM) or coronary angiography; however, they were more commonly intubated and on vasopressor therapy as compared to patients who did not have a COVID-19 infection. CONCLUSIONS: This meta-analysis showed that IHCA with COVID-19 has a higher mortality and lower rates of ROSC compared with non-COVID-19 IHCA. COVID-19 is an independent risk factor for poor outcomes in IHCA patients.

Comparative assessment of safety with leadless pacemakers compared to transvenous pacemakers: a systemic review and meta-analysis.

BACKGROUND: Leadless pacemakers (LP) and transvenous pacemakers (TVP) are two stable pacing platforms currently available in clinical practice. Observational data show mixed results with regards to their comparative safety. This meta-analysis was aimed to evaluate the comparative safety of LP over TVP. METHODS: The study protocol was registered in PROSPERO registry (CRD42022325376). Six databases were searched for published literature from inception to April 12, 2022. RevMan 5.4.1 was used for statistical analysis. Odds ratio (OR) and mean difference were used to estimate the outcome with a 95% confidence interval (CI). RESULTS: A total of 879 studies were imported from the databases. Among these, 41 papers were screened for full text and 17 meet the inclusion criteria. Among them, pooled results showed 42% lower odds of occurrence of complications in the LP group (OR 0.58, CI 0.42-0.80) compared to TVP group. Notably, 70% lower odds of device dislodgment (OR 0.30, CI 0.21-0.43), 46% lower odds of re-intervention (OR 0.54, CI 0.45-0.64), 87% lower odds of pneumothorax (OR 0.13, CI 0.03-0.57), albeit, 2.65 times higher odds of pericardial effusion (OR 2.65, CI 1.49-4.70) were observed in the LP group. CONCLUSIONS: This meta-analysis showed LP to be a significantly safer modality compared to TVP, in terms of re-intervention, device dislodgment, pneumothoraxes, and overall complications. However, there were higher rates of pericardial effusion in the LP group. There was a diverse number of patients included, and all studies were observational. Randomized trials are needed to validate our findings.

Catheter ablation using pulmonary vein isolation with versus without left atrial posterior wall isolation for persistent atrial fibrillation: an updated systematic review and meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF); however, the results are suboptimal for persistent AF. The left atrial posterior wall (LAPW) is thought to be a major additional area in initiation and perpetuation of persistent AF. Therefore, adjunctive ablation of the posterior wall may reduce AF recurrence in patients with persistent AF. OBJECTIVE: The objective of this study was to compare outcomes of catheter ablation in patients with persistent AF using PVI alone versus a combination of PVI and LAPW isolation. METHODS: Literature search was conducted in PubMed, PubMed Central, Scopus, and Embase since inception to February 2023. Screening of studies was done via Covidence software. Risk of bias assessment was done using appropriate tools. Data extraction and a narrative synthesis were carried out accordingly. RESULTS: Ten studies were included, of which five were randomized controlled trials. PVI with LAPW ablation group had significantly lower recurrence of overall atrial tachyarrhythmia (OR 0.47, CI 0.32-0.70) and AF (OR 0.39, CI 0.23-0.69). In sensitivity analysis, freedom from atrial arrhythmias was noted to be significantly higher in the PVI with LAPW ablation group (OR 2.22, CI 1.36-3.64). However, there was no significant difference in occurrence of atrial flutter (OR 1.36, CI 0.86-2.14) or with periprocedural adverse events (OR 1.10, CI 0.60-1.99). CONCLUSION: LAPW ablation, in addition to PVI, significantly improves the rates of arrhythmia freedom and reduces the recurrence of overall atrial tachyarrhythmia. There was no significant difference in atrial flutter or periprocedural adverse events.

Differences in treatment and outcomes among patients with ST-segment elevation myocardial infarction with and without standard modifiable risk factors: a systematic review and meta-analysis.

There are limited data available on outcomes and pathophysiology behind ST-segment elevation myocardial infarction (STEMI) in populations without standard modifiable risk factors (SMuRFs). The authors carried out this meta-analysis to understand the differences in treatment and outcomes of STEMI patients with and without SMuRFs. Methods: A systematic database search was performed for relevant studies. Studies reporting desired outcomes among STEMI patients with and without SMuRFs were selected based on predefined criteria in the study protocol (PROSPERO: CRD42022341389). Two reviewers independently screened titles and abstracts using Covidence. Full texts of the selected studies were independently reviewed to confirm eligibility. Data were extracted from all eligible studies via a full-text review of the primary article for qualitative and quantitative analysis. In-hospital mortality following the first episode of STEMI was the primary outcome, with major adverse cardiovascular events (MACE), repeat myocardial infarction (MI), cardiogenic shock, heart failure, and stroke as secondary outcomes of interest. Odds ratio (OR) with a 95% CI was used to estimate the effect. Results: A total of 2135 studies were identified from database search, six studies with 521 150 patients with the first STEMI episode were included in the analysis. The authors found higher in-hospital mortality (OR: 1.43; CI: 1.40-1.47) and cardiogenic shock (OR: 1.59; 95% CI: 1.55-1.63) in the SMuRF-less group with no differences in MACE, recurrent MI, major bleeding, heart failure, and stroke. There were lower prescriptions of statin (OR: 0.62; CI: 0.42-0.91) and Angiotensin converting enzyme inhibitor /Angiotensin II receptor blocker (OR: 0.49; CI: 0.28-0.87) at discharge in SMuRF-less patients. There was no difference in procedures like coronary artery bypass graft, percutaneous coronary intervention, and thrombolysis. Conclusion: In the SMuRF-less STEMI patients, higher in-hospital mortality and treatment discrepancies were noted at discharge.

Heart failure clinical trial enrollment at a rural satellite hospital.

INTRODUCTION: Heart failure is a clinical condition that notably affects the lives of patients in rural areas. Partnering of a rural satellite hospital with an urban academic medical center may provide geographically underrepresented populations with heart failure an opportunity to access to controlled clinical trials (CCTs). METHODS: We report our experience in screening, consenting and enrolling subjects at the VCU Health Community Memorial Hospital (VCU-CMH) in rural South Hill, Virginia, that is part of the larger VCU Health network, with the lead institution being VCU Health Medical College of Virginia Hospitals (VCU-MCV), Richmond, VA. Subjects were enrolled in a clinical trial sponsored by the National Institutes of Health and assigned to treatment with an anti-inflammatory drug for heart failure or placebo. We used the electronic health record and remote guidance and oversight from the VCU-MCV resources using a close-loop communication network to work with local resources at the facility to perform screening, consenting and enrollment. RESULTS: One hundred subjects with recently decompensated heart failure were screened between January 2019 and August 2021, of these 61 are enrolled to date: 52 (85%) at VCU-MCV and 9 (15%) at VCU-CMH. Of the subjects enrolled at VCU-CMH, 33% were female, 77% Black, with a mean age of 52 ± 10 years. CONCLUSION: The use of a combination of virtual/remote monitoring and guidance of local resources in this trial provides an opportunity for decentralization and access of CCTs for potential novel treatment of heart failure to underrepresented individuals from rural areas. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03797001.

Preventing the Next Pandemic: Is Live Vaccine Efficacious against Monkeypox, or Is There a Need for Killed Virus and mRNA Vaccines?

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods and Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses-ACAM2000, JYNNEOS, and LC16-with the first being a replicating vaccine and the latter being non- or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental immunity to MPV. ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer complications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or developed into a mRNA vaccine before monkeypox is declared a pandemic.

Plasma exchange with immunosuppression in pulmonary alveolar haemorrhage due to leptospirosis.

BACKGROUND & OBJECTIVES: Pulmonary involvement due to leptospirosis carries high case fatality rate and is the commonest cause of death due to leptospirosis. Immune mechanisms play a key role in the pathogenesis of leptospiral pulmonary haemorrhage. As other immune pulmonary haemorrhages due to non leptospiral causes are treated with plasma exchange and cyclophosphamide we evaluated their efficacy in patient with leptospiral pulmonary haemorrhage. METHODS: Of the 602 confirmed patients of leptospirosis, 236 (39.2%) had pulmonary haemorrhage. Of these,144 had mild haemorrhage (acute lung injury score < 2.5) and were included in the study. One hundred and fourteen patients were given two cycles of plasma exchange, 24 h apart, 25 ml/kg body weight of plasma was removed in each cycle. Cyclophosphamide (20 mg/kg body weight) was given after the first plasma exchange cycle. The remaining 30 patients were not given this treatment, and used as control. RESULTS: In the control group only 5 (16.6%) patients survived while in the treatment group 70 (61.40%) patients survived. Thrombocytopenia was observed in 111 (77.08%) patients. Renal and hepatic involvement was seen but did not account for mortality. Minor complications were seen in group I patients after plasma exchange and cyclophosphamide treatment, but none were serious. INTERPRETATION & CONCLUSIONS: Our findings showed that plasma exchange with immunosuppression improved survival in patients of pulmonary alveolar haemorrhage due to leptospirosis, suggesting that immune mechanisms play a key role in the pathogenesis of the disease.

Peripheral Arterial Disease in Women: The Gender Effect.

Peripheral arterial disease (PAD) is a common atherosclerotic disease approximately affecting 8.5 million Americans above age 40 and is associated with significant functional impairment, morbidity and mortality from both cardiovascular and non-cardiovascular causes. PAD has increasing prevalence in females contrary to previous findings. Compared to men, women with PAD are more asymptomatic or have atypical symptoms. Women with PAD have increased quality of life impairment, increased risk of depression and increased cardiovascular mortality. The intent of this review is to provide an update on gender differences in PAD that can help in timely diagnosis and appropriate management through intensive cardiovascular risk factor modification, exercise program and guideline directed therapy to improve cardiovascular outcomes.

Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale-Associated Stroke.

Importance: Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Observations: Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. Conclusions and Relevance: These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.