Long-term Survival Following Heart Transplantation for Chagas Versus Non-Chagas Cardiomyopathy: A Single-center Experience in Northeastern Brazil Over 2 Decades.

Data on post-heart transplant (HT) survival of patients with Chagas cardiomyopathy (CC) are scarce. We sought to evaluate post-HT survival in patients with CC as compared with other causes of heart failure across different eras of HT. Methods: We conducted a retrospective, cohort study of 376 adult HT recipients between October 1997 and November 2019. Participants were classified according to the etiology of heart failure as CC (N = 66), nonischemic cardiomyopathy (N = 214), and ischemic cardiomyopathy (N = 96), and according to the era of HT as early (1997-2009), recent (2010-2014), and current era (2015-2019). Results: After a mean follow-up of 5.0 y (0-20.5 y), post-HT survival rates at 1, 5, and 10 y were comparable between groups. One-y survival improved from 70% in the early eras to 80% in the current era (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = 0.034). After adjustment for sex, age, and mechanical circulatory support, time-related improvement in survival was observed only in patients without CC (HR, 0.54; 95% CI, 0.32-0.91; P = 0.019) but not in those with CC (HR, 0.99; 95% CI, 0.36-2.73; P = 0.98). Causes of death were similar between patients with CC and the other etiological subgroups. Conclusions: Posttransplant survival is comparable between patients with CC, nonischemic cardiomyopathy, and ischemic cardiomyopathy. Although survival has improved significantly over years for most HT recipients, it has remained unchanged for those with Chagas disease. These trends underscore the importance of scientific research, policy discussions and a collaborative registry of heart transplantation in Chagas cardiomyopathy.

A systematic review and meta-analysis of delayed coronary artery access for coronary angiography with or without percutaneous coronary intervention (PCI) in patients who underwent transcatheter aortic valve replacement (TAVR).

Coronary artery disease (CAD) and severe aortic valve stenosis frequently coexist. Given the progressive nature of CAD, silent or non-significant CAD may become symptomatic or functionally relevant years after TAVR. However, there is a paucity of data documenting the feasibility of either coronary angiography and/or PCI after TAVR. We systematically searched Medline, Pubmed, Embase, Cochrane database, Google Scholar, Science Direct, Web of Science, and conference abstracts from conception to March 2020 using OvidSP in TAVR patients undergoing coronary angiography with or without PCI at least 6 months after TAVR. Patients and procedural characteristics were summarized. The primary outcome of interest was successful coronary angiography for either the left main coronary artery (LMCA) or right coronary artery (RCA) with or without PCI. Pooled estimates were calculated using a random-effects meta-analysis. The study protocol was registered in PROSPERO. Eleven reports for a total of 696 coronary angiograms and 287 PCI were included in the analysis. Patients were slightly predominantly male, older and had a mean left ventricular ejection fraction of more than 50% with an intermediate STS. The summary estimate rates of successful LMCA and RCA angiography with a Medtronic self-expandable valve (SEV) were 84% (95% CI 73-90%, I2 = 79, p = 0.015) and 69% (95% CI 37-89%, I2 = 86, p = 0.23), respectively, while with the Edwards Lifesciences balloon expandable valve (BEV), the summary estimate rates for successful LMCA and RCA angiography were 94% (95% CI 72-99%, I2 = 66, p = 0.003) and 95% (95% CI 48-99%, I2 = 83, p = 0.05), respectively. The summary estimate rate of successful PCI post TAVR with either a Medtronic SEV or Edwards Lifesciences BEV was 93% (95% CI 86-96%, I2 = 33, p = 0.0001). The overall achievement of a successful coronary angiography with or without PCI in post-TAVR patients is high, with a lower success rate for RCA angiography in patients with the Medtronic SEV Mortality and bleeding did not differ in our analysis.

Laser Atherectomy to Treat Severe In Stent Restenosis of the Superior Mesenteric Artery.

Chronic mesenteric ischemia is an uncommon disorder in the USA. Frequently, a percutaneous approach is the first therapeutic choice to reduce its symptoms and improve outcomes. After an initial treatment with stents, further interventions might be necessary to address in-stent restenosis and re-establish a better visceral flow. Using laser atherectomy in a similar fashion as used in the peripheral arteries, has proven to be safe helping to achieve a desired final result. We present a case of chronic mesenteric ischemia in a 53-year-old man caused by severe in-stent restenosis who had abdominal pain and weight loss. We used a 0.9 mm laser catheter with low energy and pulse rate as an adjunct to balloon therapy. After revascularization, the patient's symptoms improved dramatically. To the best of our knowledge, this is the first published case in which atherectomy with laser was used to treat severe in-stent restenosis of a mesenteric vessel in chronic mesenteric ischemia. Learning Objective The treatment of severe in-stent restenosis of the superior mesenteric artery using laser atherectomy is safe and can give excellent results when traditional percutaneous therapies fail.

Metaanalysis of Multivessel vs Culprit Artery Only Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction.

Background: Primary percutaneous coronary intervention (PCI) is the most frequently used treatment modality for patients presenting with ST elevation myocardial infarction (STEMI). Current professional society guidelines recommend culprit artery only PCI. Recent evidence suggests the potential benefit of multivessel PCI among patients with STEMI that is not complicated by cardiogenic shock. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical studies of patients with STEMI, not complicated by cardiogenic shock, who underwent primary PCI between January 1966 and January 2018. We evaluated all-cause and cardiovascular mortality, reinfarction, and repeat revascularization among patients randomized to a multivessel PCI strategy compared to a culprit artery only PCI strategy. Results: Four randomized clinical trials with a total of 1,044 patients met the inclusion criteria. Five hundred and sixty-six patients underwent multivessel PCI, and 478 patients underwent culprit artery only PCI. Multivessel PCI reduced all the studied endpoints: total death, cardiac death, reinfarction, and repeat revascularization (all P values <0.05). Conclusion: To our knowledge, this is the largest metaanalysis of randomized controlled trials studying multivessel PCI vs culprit artery only PCI in STEMI patients without shock, among whom lesion severity was graded by angiography alone. We found that compared to culprit artery only PCI, the multivessel PCI strategy was beneficial in reducing all-cause and cardiovascular mortality, reinfarction, and the need for repeat revascularization.

Vascular brachytherapy versus drug-eluting stents in the treatment of in-stent restenosis: A meta-analysis of long-term outcomes.

INTRODUCTION: Clinical trials have shown a short-term benefit of drug-eluting stents (DES) compared to vascular brachytherapy (VBT) for treatment of in-stent restenosis (ISR). The long-term benefits of DES vs. VBT are conflicting in the literature. This study aimed to do a meta-analysis of long-term outcomes of DES compared to VBT for treatment of ISR. METHODS: PubMed, EMBASE, Cochrane Central and unpublished data were searched for cohort studies and randomized controlled trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We evaluated the following outcomes at 2-5 years of follow-up: target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall mortality. Heterogeneity was defined as I(2) values > 25%. Review Manager 5.1 was used for statistical analysis. RESULTS: We included 1,375 patients from five studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%) patients. After a 2-5 year follow-up, no significant differences were found between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55-3.63; P < 0.001) and TVR (OR 2.23; CI 1.01-4.94; P = 0.05) were significantly increased in patients who received VBT. CONCLUSION: This study suggests that DES are associated with decreased long-term revascularization procedures when compared to VBT for the treatment of ISR. This benefit does not appear to be associated with a significant reduction in mortality or myocardial infarction.

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis.

BACKGROUND: Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. METHODS: We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values inferior to 0.10 and I(2) >25% were considered significant for heterogeneity. RESULTS: We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. CONCLUSIONS: The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.

Neck circumference is not associated with subclinical atherosclerosis in retired National Football League players.

BACKGROUND: Neck circumference (NC) is associated with metabolic syndrome (MetS) in the general population. It is not known if NC is associated with MetS and subclinical atherosclerosis in retired National Football League (NFL) players. HYPOTHESIS: We hypothesized that NC is associated with MetS and subclinical atherosclerosis (assessed as coronary artery calcium [CAC] and carotid artery plaque [CAP]) in retired NFL players. METHODS: NC was measured midway between the midcervical spine and midanterior neck in 845 retired NFL players. CAC presence was defined as total CAC score >0. CAP was defined as carotid plaque of at least 50% greater than that of the surrounding vessel wall, with a minimal thickness of at least 1.2 mm on carotid ultrasound. Logistic regression analysis was used for the association of NC with CAC or CAP. RESULTS: Of the participants, 21% had MetS. CAC and CAP were present in 62% and 56%, respectively. Those with MetS had a higher median NC than those without MetS (17 vs 16 inches, P < 0.0001). NC was not associated with the presence of CAC or CAP in an unadjusted model and after adjusting for age, race, and cardiometabolic risk factors (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.94-1.31 for CAC; OR: 0.96, 95% CI: 0.82-1.12 for CAP per 1-standard deviation increase in NC [3.8 inches]). The results were similar when the predictor variable was NC indexed to body mass index. CONCLUSIONS: In retired NFL players with a high prevalence of CAC and CAP, NC was not associated with coronary or carotid subclinical atherosclerosis. NC may not be the most appropriate risk marker for atherosclerosis.

c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.

The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In the present work we investigated the effects of c-Myc knockdown in endothelial cell functions essential for angiogenesis to define its role in the vasculature. We provide the first evidence that reduction in c-Myc expression in endothelial cells leads to a pro-inflammatory senescent phenotype, features typically observed during vascular aging and pathologies associated with endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation and tube formation. These functional defects were associated with morphological changes, increase in senescence-associated-ß-galactosidase activity, upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells in G1-phase, indicating that c-Myc knockdown in endothelial cells induces senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed that senescent phenotype was accompanied by significant upregulation of growth factors, adhesion molecules, extracellular-matrix components and remodeling proteins, and a cluster of pro-inflammatory mediators, which include Angptl4, Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines, transcription factors known to be involved in growth control (E2f1, Id1 and Myb) were downregulated, while those involved in inflammatory responses (RelB, Stat1, Stat2 and Stat4) were upregulated. Our results demonstrate a novel role for c-Myc in the prevention of vascular pro-inflammatory phenotype, supporting an important physiological function as a central regulator of inflammation and endothelial dysfunction.

Cyclooxygenase-2 contributes to functional changes seen on experimental hemorrhagic cystitis induced by ifosfamide in rat urinary bladder.

PURPOSE: Ifosfamide (IFS) is often involved in the occurrence of hemorrhagic cystitis due to direct contact of its metabolite acrolein with uroepithelium. It has been shown that COX-2 is involved in this pathogenesis. Thus, we aimed to study the functional changes on the urinary bladder in the putative modifications induced by IFS, as well as the COX-2 role in this process. MATERIALS AND METHODS: IFS-treated rats were evaluated by cystometrography in absence or presence of COX inhibitors indomethacin or etoricoxib or in the presence of mesna. Experiments with isolated strips of urinary bladder obtained from animals with IFS-induced cystitis, either treated or not treated with COX inhibitors or mesna, were performed. Histological analyses, immunohistochemistry for COX-2, and measurement of plasma PGE(2) were also performed. RESULTS: IFS treatment caused severe inflammation of the bladder tissue. Cystometrography recordings of IFS-treated rats revealed bladder with increased micturition frequency and enhanced filling intravesical pressure. Contractility of the isolated smooth muscle from the rat's bladder with IFS-induced cystitis showed decreased force development in response to KCl and CCh. Almost all effects induced by IFS were ameliorated by the use of COX inhibitors or mesna. Enzyme expression in the urinary bladder tissue was positive, and plasma concentration of PGE(2) was increased in IFS-treated animals and decreased significantly in etoricoxib-treated animals. CONCLUSIONS: IFS causes important changes in the micturition physiology in rats, and the inhibition of the isoenzyme COX-2 could be an important event that could prevent the detrimental effects elicited by IFS-induced hemorrhagic cystitis.