The effect of colchicine on cholesterol crystal formation, expansion and morphology: a potential mechanism in atherosclerosis.

Background: Inflammation is pivotal to the progression of atherosclerosis. Cholesterol crystals (CCs) that grow and enlarge within the plaque core can cause plaque rupture and trigger inflammation as they deposit into the atherosclerotic bed. Thus, agents that affect CC formation, expansion, and morphology may reduce cardiovascular (CV) risk independent of lipid-lowering and anti-inflammatory therapy. Objective: Because colchicine is highly concentrated in leukocytes that can enter the atherosclerotic plaque core, we tested its effect on the formation and growth of CCs in bench experiments to determine whether it may have direct effects on CCs, independent of its known anti-inflammatory actions. Method: Different dosages of colchicine mixed with cholesterol (0.05-5 mg/ml/g of cholesterol) were used to influence the formation CCs and volume expansion in vitro. These were compared to control samples with cholesterol in ddH2O without colchicine. In an ex vivo study, fresh atherosclerotic human plaques were incubated with and without colchicine in a water bath at 37°C for 48 h to assess the impact of colchicine on CC morphology. Scanning electron microscopy (SEM) was utilized to analyze CC morphology in samples from the various treatment groups. Results: The addition of colchicine to cholesterol caused a substantial dose-dependent reduction in volume (p < 0.05). Pairwise comparisons of volume reduction, showed a significant reduction in volume at 5 mg/ml/g when compared to control (p < 0.02) but the calculated Cohen's d effect size was large for five of the six pairwise comparisons. By SEM, CCs from both in vitro and ex vivo samples treated with colchicine had evidence of dissolution and changes in their morphology as evidenced by the loss of their sharp edges. In contrast, CCs in untreated specimens retained their typical geometric structure. Conclusions: Colchicine can reduce CC formation and expansion and alter CC morphology. These previously unappreciated effects of colchicine may contribute to its clinical benefit in patients with CV disease independent of its anti-inflammatory effects.

Clinical outcomes between direct oral anticoagulants versus vitamin K antagonists in chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis.

Pulmonary hypertension (PH) is a known chronic condition that can lead to increased morbidity and mortality. Patients who develop PH due to thromboembolic disease are catalogued as chronic thromboembolic pulmonary hypertension (CTEPH). Anticoagulation remains a topic of interest in these patients. PUBMED, EMBASE and COCHRANE databases were searched by two investigators until December 2023. Information was analyzed for all-cause mortality, venous thromboembolism and major bleeding. We included a total of 10 studies in this meta-analysis. Our pooled analysis demonstrated that DOACs were non-inferior in all-cause mortality [OR 0.88, 95 % CI (0.48, 1.61)], venous thromboembolism [OR 1.00, 95 % CI (0.50, 1.98)] and major bleeding [OR 0.78, 95 % CI (0.43, 1.40)] when compared to VKAs. In conclusion, our meta-analysis supports the use of DOACs in patients with CTEPH. Further randomized trials are still needed to confirm our results in terms of safety and mortality.

Transcatheter Vacuum-Assisted Mass Extraction Versus Surgical Debridement for Vegetations in Tricuspid Valve Infective Endocarditis: A Meta-Analysis of Observational Studies.

Tricuspid valve infective endocarditis (TVIE), often associated with vegetation in people who inject drugs, has introduced a less invasive option for vegetation removal: transcatheter vacuum-assisted mass extraction (TVME). This technique is emerging as an alternative to standard surgical debridement (SD) and valve repair. However, the comparative effectiveness of TVME versus SD in treating TVIE has yet to be investigated. A comprehensive systematic literature search was performed on PubMed, Embase, and Cochrane to identify all relevant studies comparing TVME with SD in patients with TVIE. The search covered studies from inception up to August 15, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random-effects model to calculate risk ratios (RRs), mean differences, and 95% confidence intervals (CIs). Five studies included a total of 431 patients (244 in the TVME arm and 187 in the SD arm). In-hospital mortality (p = 0.72), procedural mortality (p = 0.77), 30-day mortality (p = 0.25), and 1-year mortality (p = 0.44) insignificantly favored SD over TVME. Overall mortality across the 5 studies insignificantly favored TVME over SD (RR = 0.66, 95% CI 0.31 to 1.39, p = 0.27, I2 = 57%). When addressing heterogeneity by excluding 1 study, no statistical significance in the difference between the 2 arms regarding overall mortality was observed (RR 0.99, 95% CI 0.60 to 1.63, p = 0.97, I2 = 0%). This meta-analysis of the 5 observational studies found no significant difference in overall mortality between TVME and SD for the treatment of TVIE. However, prospective randomized controlled trials are necessary to further understand and compare the outcomes of these 2 approaches.

Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1ß, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-ß by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 µg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 µg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-ß compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. Conclusions: These findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.

Cholesterol crystal formation is a unifying pathogenic mechanism in the development of diabetic retinopathy.

AIMS/HYPOTHESIS: Hyper-reflective crystalline deposits found in retinal lesions have been suggested to predict the progression of diabetic retinopathy, but the nature of these structures remains unknown. METHODS: Scanning electron microscopy and immunohistochemistry were used to identify cholesterol crystals (CCs) in human donor, pig and mouse tissue. The effects of CCs were analysed in bovine retinal endothelial cells in vitro and in db/db mice in vivo using quantitative RT-PCR, bulk RNA sequencing, and cell death and permeability assays. Cholesterol homeostasis was determined using 2H2O and 2H7-cholesterol. RESULTS: We identified hyper-reflective crystalline deposits in human diabetic retina as CCs. Similarly, CCs were found in the retina of a diabetic mouse model and a high-cholesterol diet-fed pig model. Cell culture studies demonstrated that treatment of retinal cells with CCs can recapitulate all major pathogenic mechanisms leading to diabetic retinopathy, including inflammation, cell death and breakdown of the blood-retinal barrier. Fibrates, statins and α-cyclodextrin effectively dissolved CCs present in in vitro models of diabetic retinopathy, and prevented CC-induced endothelial pathology. Treatment of a diabetic mouse model with α-cyclodextrin reduced cholesterol levels and CC formation in the retina, and prevented diabetic retinopathy. CONCLUSIONS/INTERPRETATION: We established that cholesterol accumulation and CC formation are a unifying pathogenic mechanism in the development of diabetic retinopathy.

Management of Atrial Fibrillation Post Transcatheter Aortic Valve Implantation.

Atrial fibrillation (AF) is a common complication in patients who underwent transcatheter aortic valve implantation. Some of these patients have preexisting AF as well. The management of these patients is complex, especially after the procedure, when there is a sudden change in hemodynamics. There are no established guidelines about the management of the patients who underwent transcatheter aortic valve replacement with preexisting or new-onset AF. This review article discusses the management of these patients with rate and rhythm control strategies with medications. This article also highlights the role of newer oral anticoagulation medications and left atrial occlusion devices to prevent stroke after the procedure. We will also discuss new advances in the care of this patient population to prevent the occurrence of AF after transcatheter aortic valve implantation. In conclusion, this article is a synopsis of both pharmacologic and device interventions for the management of AF in patients who underwent transcatheter aortic valve replacement.

Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis.

BACKGROUND: Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown. METHODS: Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). RESULTS: Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%). CONCLUSION: Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

Interaction between bacteria and cholesterol crystals: Implications for endocarditis and atherosclerosis.

BACKGROUND: The interaction between pathogenic bacteria and cholesterol crystals (CCs) has not been investigated. However, CCs are found extensively in atherosclerotic plaques and sclerotic cardiac valves. Interactions between pathogenic bacteria and CCs could provide insights into destabilization of atherosclerotic plaques and bacterial adhesion to cardiac valves. METHODS: Staphylococcus aureus and Pseudomonas aeruginosa were used to assess in vitro bacterial adhesion to CCs and proliferation in the presence of CCs compared to plastic microspheres and glass shards as controls. Ex vivo studies evaluated bacterial adhesion to atherosclerotic rabbit arteries compared to normal arteries and human atherosclerotic carotid plaques compared to normal carotid arteries. Scanning electron microscopy (SEM) was used to visualize bacterial adhesion to CCs and confocal microscopy was used to detect cholesterol binding to bacteria grown in the presence or absence of CCs. RESULTS: In vitro, S. aureus and P. aeruginosa displayed significantly greater adhesion, 36% (p<0.0001) and 89% (p<0.0001), respectively, and growth upon exposure to CCs compared to microspheres or glass shards. Rabbit and human atherosclerotic arteries contained significantly greater bacterial burdens compared to controls (4× (p<0.0004); 3× (p<0.019), respectively. SEM demonstrated that bacteria adhered and appeared to degrade CCs. Consistent with this, confocal microscopy indicated increased cholesterol bound to the bacterial cells. CONCLUSIONS: This study is the first to demonstrate an interaction between bacteria and CCs showing that bacteria dissolve and bind to CCs. This interaction helps to elucidate adhesion of bacteria to sclerotic valves and atherosclerotic plaques that may contribute to endocarditis and plaque destabilization.

Left Atrial Appendage Closure Versus Oral Anticoagulation in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Left atrial appendage closure (LAAC) devices are an alternative therapy in non-valvular atrial fibrillation (NVAF) patients with contraindications to oral anticoagulation (OAC). However, there are limited data about the clinical outcomes of LAAC devices compared to medical treatment. METHODS: A comprehensive research for studies comparing LAAC devices and OAC for patients with NVAF was performed from inception to January 1, 2021. A meta-analysis was performed using a random effect model to calculate odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: Five studies were eligible that included a total of 4778 patients with a median-weighted follow-up period was 2.6 years. Compared to OAC, the LAAC device arm was associated with a lower risk of the composite of stroke, systemic embolism, and cardiovascular death (OR 0.71; 95% CI 0.51-1.00; p = 0.05). LAAC device arm was also associated with a lower risk of all-cause mortality (OR of 0.60, 95% CI 0.46-0.77; p < 0.0001), cardiovascular mortality (OR of 0.57, 95% CI 0.46-0.70; p < 0.00001), hemorrhagic stroke (OR of 0.19, 95% CI 0.07-0.50; p= 0.0006), all major bleeding (OR of 0.61, 95% CI 0.43-0.88; p = 0.007) and non-procedural major bleeding (OR of 0.46, 95% CI 0.32-0.65; p < 0.0001). There was no significant difference in all stroke, ischemic stroke, and systemic embolization between the two groups. CONCLUSIONS: Our meta-analysis showed lower all-cause mortality, cardiovascular mortality, hemorrhagic stroke, major bleeding, non-procedural major bleeding and the composite of stroke, systemic embolism, and cardiovascular death in the LAAC device arm when compared to OAC. However, the risk of all stroke, ischemic stroke, and systemic embolism were similar between the two arms.

Patent Foramen Ovale Closure and Decompression Sickness Among Divers.

BACKGROUND: Decompression sickness is a diving-related disease that results in various clinical manifestations, ranging from joint pain to severe pulmonary and CNS affection. Complications of this disease may sometimes persist even after treatment with hyperbaric oxygen therapy. In addition, it may hamper the quality of life by forcing divers to restrict their recreational practice. The presence of a patent foramen ovale (PFO) increases the risk of decompression sickness by facilitating air embolization. Therefore, PFO closure may play a role in reducing such complications. However, PFO closure remains associated with its own set of risks and complications. We sought to assess the benefit and harm of PFO closure for the prevention of decompression sickness in divers. METHODS: We conducted a comprehensive search of MEDLINE, Embase, CENTRAL, and Web of Science. Two-armed studies comparing the incidence of decompression sickness with or without PFO closure were included. We used a random-effects model to compute risk ratios comparing groups undergoing PFO closure to those not undergoing PFO closure. RESULTS: Four observational studies with a total of 309 divers (PFO closure: 141 and no closure: 168) met inclusion criteria. PFO closure was associated with a significantly lower incidence of decompression sickness (PFO-closure: 2.84%; no closure: 11.3%; RR: 0.29; 95% CI: 0.10 to 0.89; NNTB = 11), with low heterogeneity (I2 = 0%). The mean follow-up was 6.12 years (Standard deviation 0.70). Adverse events occurred in 7.63% of PFO closures, including tachyarrhythmias and bleeding. CONCLUSION: PFO closure may potentially reduce the risk of decompression sickness among divers; however, it is not free of potential downsides, with nearly one in thirteen patients in our analysis experiencing an adverse event.

Left Atrial Appendage Closure During Cardiac Surgery for Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Left atrial appendage closure (LAAC) during cardiac surgery in atrial fibrillation (AF) patients has been investigated in multiple studies with variable safety and efficacy results. METHODS: A comprehensive review was performed of all studies comparing LAAC and placebo arm during cardiac surgery in AF patients. A random-effect model was used to calculate risk ratios, mean differences, and 95% confidence intervals. RESULTS: Five randomized controlled trials and 22 observational studies were included with a total of 540,111 patients. The LAAC group had significantly decreased postoperative stroke/embolic events as compared to the no LAAC group with all cardiac surgeries (3.74% vs 4.88%, p = 0.0002), isolated valvular surgery (1.95% vs 4.48%, p = 0.002). However, CABG insignificantly favored the LAAC group for stroke/embolic events (6.72% vs 8.30%, p = 0.07). There was no difference between both groups in all-cause mortality in the perioperative period (p = 0.42), but was significantly lower in the LAAC arm after two years (14.1% vs 18.3%, p = 0.02). There was no difference in major bleeding, all-cause rehospitalizations, or cross-clamp time between both groups (p = 0.53 and p = 0.45). The bypass and the cross-clamp time were longer in the LAAC group (4 and 9 min, respectively). CONCLUSION: In AF patients, LAAC during cardiac surgery had a decreased risk of stroke and long-term all-cause mortality. Additionally, there was no difference in major bleeding, all-cause rehospitalizations, or cross-clamp time.

Effect of aspirin on cholesterol crystallization: A potential mechanism for plaque stabilization.

Background and aims: Cholesterol crystals (CCs) have been found to be critical in the evolution and progression of atherosclerotic plaque leading up to rupture. This includes triggering inflammation and mechanically traumatizing the plaque and surrounding tissues. Thus, inhibition of crystal formation and degrading the crystals could be an important therapeutic approach in the prevention of cardiovascular events. Because of its physico-chemical properties we examined the effect of aspirin (ASA) on cholesterol crystallization. Methods: A first experiment tested three amounts of cholesterol (1, 2, 3 g) with a wide range of ASA (0-60 mg) on cholesterol crystallization and volume expansion. A second experiment tested the effect of CCs with and without ASA in perforation of fibrous membrane during crystallization. A third experiment evaluated the effect of ASA on melting CCs in human atherosclerotic plaques. Scanning electron microscopy (SEM) was used to evaluate crystal morphology. Results: Aspirin significantly inhibited cholesterol crystallization and volume expansion in a dose related fashion and even at physiologic levels (0.3 mg/ml). Moreover, ASA prevented perforation of fibrous membranes. By SEM, crystals in human atherosclerotic plaques were found melted with ASA. Conclusions: Cholesterol volume expansion during crystallization was significantly inhibited and CCs were dissolved in the presence of ASA. Fibrous membranes were not perforated with ASA because of both these effects.

The impact of statin therapy and aerobic exercise training on skeletal muscle and whole-body aerobic capacity.

BACKGROUND: Statin use is widely recognized for improving cardiovascular health, but questions remain on how statin use influences skeletal muscle, particularly mitochondrial function. STUDY OBJECTIVE DESIGN AND PARTICIPANTS: The influence of statin therapy and exercise (EX) on aerobic capacity was determined. In Study1, skeletal muscle aerobic capacity was measured before and after 80 mg atorvastatin therapy. In Study2, aerobic capacity (skeletal muscle and whole body) was measured before and after a 12-week exercise randomized control trial in older adults (age = 67 ± 5 yrs.), a subset of which were on chronic low-moderate intensity statin therapy. MAIN OUTCOME MEASURES: Muscle oxidative capacity was determined from the phosphocreatine recovery rate constant (kPCr) using 31P Magnetic Resonance Spectroscopy. Whole body peak oxygen uptake (VO2 peak) was measured during a graded exercise test with indirect calorimetry. RESULTS: High dose statin therapy resulted in a 12% reduction in muscle oxidative capacity (pre = 1.34 ± 0.34 min-1, post = 1.17 ± 0.25 min-1, p = 0.004). Similarly, chronic low-moderate dose statin therapy was associated with lower muscle oxidative capacity at baseline (1.50 ± 0.35 min-1) compared to non-statin users (1.88 ± 0.047 min-1, p = 0.019). Following EX, muscle oxidative capacity increased by 35-40% (statin: Pre: 1.39 ± 0.44 vs. Post: 1.88 ± 0.47 min-1, no statin Pre: 1.86 ± 0.58 vs. Post: 2.58 ± 0.85 min-1) compared to control groups (Pre: 1.74 ± 0.27 vs Post: 1.75 ± 0.49 min-1, p = 0.001). VO2 peak increased by 11% for EX groups (Pre: 18.8 ± 2.8 vs. Post: 20.8 ± 3.0 ml·kg-1·min-1) following training compared to a small decline in controls (Pre: 21.8 ± 3.7 vs. Post: 20.8 ± 3.04 ml·kg-1·min-1, p = 0.001). CONCLUSIONS: Statin therapy resulted in reduced muscle oxidative capacity. Aerobic exercise improved skeletal muscle oxidative capacity and whole-body aerobic capacity during statin therapy.

Meta-Analysis of Valve-in-Valve Transcatheter Aortic Valve Implantation Versus Redo-surgical Aortic Valve Replacement in Failed Bioprosthetic Aortic Valve.

This meta-analysis was conducted to compare clinical outcomes of valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) versus redo-surgical aortic valve replacement (Redo-SAVR) in failed bioprosthetic aortic valves. We conducted a comprehensive review of previous publications of all relevant studies through August 2020. Twelve observational studies were included with a total of 8,430 patients, and a median-weighted follow-up period of 1.74 years. A pooled analysis of the data showed no significant difference in all-cause mortality (OR 1.15; 95% CI 0.93 to 1.43; p = 0.21), cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, and the rate of moderate to severe paravalvular leakage between ViV-TAVI and Redo-SAVR groups. The rate of major bleeding (OR 0.36; 95% CI 0.16 to 0.83, p = 0.02), procedural mortality (OR 0.41; 95% CI 0.18 to 0.96, p = 0.04), 30-day mortality (OR 0.58; 95% CI 0.45 to 0.74, p <0.0001), and the rate of stroke (OR 0.65; 95% CI 0.52 to 0.81, p = 0.0001) were significantly lower in the ViV- TAVI arm when compared with Redo-SAVR arm. The mean transvalvular pressure gradient was significantly higher post-implantation in the ViV-TAVI group when compared with the Redo-SAVR arm (Mean difference 3.92; 95% CI 1.97 to 5.88, p < 0.0001). In conclusion, compared with Redo-SAVR, ViV-TAVI is associated with a similar risk of all-cause mortality, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, and the rate of moderate to severe paravalvular leakage. However, the rate of major bleeding, stroke, procedural mortality and 30-day mortality were significantly lower in the ViV-TAVI group when compared with Redo-SAVR.

The Role of Direct Oral Anticoagulants Versus Vitamin K Antagonists in the Treatment of Left Ventricular Thrombi: A Meta-Analysis and Systematic Review.

BACKGROUND: Direct oral anticoagulants (DOACs) have a well-established role in the treatment of deep vein thrombosis and pulmonary embolism and in the reduction of thromboembolism in nonvalvular atrial fibrillation. However, limited evidence supports their role in patients with left ventricular thrombi. METHODS: The PubMed, EMBASE, and Cochrane databases were searched for relevant articles published from inception to 1 August 2020. We included studies evaluating the effect of DOACs versus vitamin K antagonists (VKAs) in patients with left ventricular thrombi. The primary outcome was thrombus resolution, and the secondary outcomes were major bleeding and stroke or systemic embolization (SSE). RESULTS: Five retrospective observational studies were included, with a total of 857 patients. VKAs and DOACs had a similar rate of thrombus resolution (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.57-1.65; p = 0.90). Our analysis also demonstrated a similar rate of major bleeding (OR 0.62; 95% CI 0.27-1.44; p = 0.27) and SSE (OR 1.86; 95% CI 0.99-3.50; p = 0.05) between the two treatment groups. CONCLUSION: In patients with left ventricular thrombi, DOACs and VKAs are associated with similar rates of thrombus resolution, major bleeding, and SSE.

Anthracycline-induced cardiotoxicity: mechanisms of action, incidence, risk factors, prevention, and treatment.

Anthracycline is a mainstay in treatment of many cancers including lymphoma and breast cancer among many others. However, anthracycline treatment can be cardiotoxic. Although anthracycline-induced cardiotoxicity is dose dependent, it can also occur early at the onset of treatment and even up to several years following completion of treatment. This review article focuses on the understanding of mechanisms of anthracycline-induced cardiotoxicity, the treatments, and recommended follow-up and preventive approaches.

Clinical Outcomes of the Self-Expandable Evolut R Valve Versus the Balloon-Expandable SAPIEN 3 Valve in Transcatheter Aortic Valve Implantation: A Meta-Analysis and Systematic Review.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now indicated in patients with symptomatic aortic stenosis and low, moderate, and high surgical risk. There are multiple types of valves available in TAVR. SAPIEN 3, and Evolut R are two of the most commonly used valves. METHODS: We conducted a systematic review and meta-analysis of all studies that compared SAPIEN 3 vs Evolut R in patients undergoing TAVR. The primary endpoint of this meta-analysis was 30-day mortality. Secondary outcomes included major of life-threatening bleeding, risk of stroke, need of permanent pacemaker implantation, and risk of moderate to severe paravalvular regurgitation (PVR). RESULTS: We included a total of 9 studies. One study was a randomized clinical trial, five were prospective observational studies and three were retrospective. 30-day mortality rate was similar between SAPIEN 3 and Evolut R (odds ratio (OR) 1.19; 95% confidence interval (CI) 0.72 to 1.93; p = 0.47). The risk of major or life-threatening bleeding (OR of 0.83, 95% CI 0.50 to 1.39; p = 0.48), and the risk of stroke (OR of 0.82, 95% CI 0.38 to 1.78; p = 0.62) were also similar between the two types of valves. Compared to SAPIEN 3, Evolut R was associated with statistically significant risk of permanent pacemaker implantation (OR of 1.40, 95% CI 1.15 to 1.70; p = 0.0007), and moderate to severe PVR (OR of 2.56, 95% CI 1.14 to 5.74; p = 0.02). CONCLUSIONS: At 30 day follow up, both Evolut R and SAPIEN 3 shared similar risks of 30-day mortality, major or life-threatening bleeding, and stroke; however greater odds of pacemaker placement implantation and moderate to severe PVR were associated with Evolut R.