Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2, which has posed a significant threat to global health. Although the infection ...is frequently asymptomatic or associated with mild symptoms, in a small proportion of patients it can produce an intense inflammatory and prothrombotic state that can lead to acute respiratory distress syndrome, multiple organ failure, and death. Angiotensin-converting enzyme 2, highly expressed in the respiratory system, has been identified as a functional receptor for severe acute respiratory syndrome coronavirus-2. Notably, angiotensin-converting enzyme 2 is also expressed in the cardiovascular system, and there are multiple cardiovascular implications of COVID-19. Cardiovascular risk factors and cardiovascular disease have been associated with severe manifestations and poor prognosis in patients with COVID-19. More important, patients with COVID-19 may have thrombotic and coagulation abnormalities, promoting a hypercoagulable state and resulting in an increased rate of thrombotic and thromboembolic events. This review will describe the pathophysiological characteristics of the cardiovascular involvement following infection by severe acute respiratory syndrome coronavirus-2, with a focus on thrombotic and thromboembolic manifestations and implications for antithrombotic management.
Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people ...aged 65 and over. Of all ageing‐related diseases, CVD are responsible for almost one‐third of deaths in the elderly, being above all cancers combined. Age is an independent and unavoidable risk factor contributing to the impairment of heart and blood vessels. As the average age of the population in industrialized countries has doubled in the last century, and almost a fifth of the world's population is predicted to be over 65 in the next decade, we can assume that the burden of CVD will fall primarily on the elderly. Evidence from basic and clinical science has shown that sex significantly influences the onset and severity of CVD. In women, CVD usually develop later than in men and with atypical symptomatology. After menopause, however, the incidence and severity of CVD increase in women, reaching equality in both sexes. Although intrinsic sexual dimorphism in cardiovascular ageing may contribute to the sex differences in CVD progression, the molecular mechanisms associated with cardiovascular ageing and their clinical value are not known in detail. In this review, we discuss the scientific knowledge available, focusing on structural, hormonal, genetic/epigenetic and inflammatory pathways, seeking to transfer these findings to the cardiovascular clinic in terms of prevention, diagnosis, prognosis and management of these pathologies and proposing possible validation of target specifics.
The different pathways involved in cardiac ageing and how they manifest in both sexes are shown in this graphic . The degree of influence of each pathway on aged men's or women's hearts is represented by the size and colour intensity of the arrows (thin and light arrows—low influence; thick and darker arrows—high influence). CVD, cardiovascular disease; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HTA, arterial hypertension; DM, diabetes mellitus; MI, myocardial infarction; RAS, renin–angiotensin system; MR, mineralocorticoid receptor; MMP2, matrix metalloproteinase 2; PLA2G7, lipoprotein‐associated phospholipase A2; HTGL, hepatic triglyceride lipase; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; TG, triglycerides; F2RL3, coagulation factor ii receptor‐like 3; CEPT, choline/ethanolamine phosphotransferase; LPL, lipoprotein lipase; INS, insulin; GNASAS, GNAS complex locus antisense transcript; ABCG1, ATP‐binding cassette, subfamily G.
Pre-eclampsia/eclampsia and hepatic rupture Vigil-De Gracia, Paulino; Ortega-Paz, Luis
International journal of gynecology and obstetrics,
September 2012, Letnik:
118, Številka:
3
Journal Article
Recenzirano
Abstract Objective To review case reports of hepatic hematoma/rupture in women with pre-eclampsia/eclampsia. Methods MEDLINE, SciELO, and LILACS databases were searched for case reports of ...pre-eclampsia/eclampsia with hepatic hematoma/rupture. Only articles written in English, Spanish, French, or Portuguese and published between 1990 and 2010 were reviewed. Results In total, 180 cases of hepatic hematoma or rupture were identified: 18 (10.0%) with subcapsular hematoma without hepatic rupture; and 162 (90.0%) with capsule rupture. Twelve (6.7%) cases were associated with eclampsia plus hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Average age was 30.9 ± 5.0 years, 74/129 (57.4%) women were parous, and cesarean delivery was performed in 132/162 (81.5%) cases. The right lobule was the most frequently affected 77/100 (77.0%). The total maternal mortality rate was 22.2% during the 21 years; however, it decreased to 16.4% in the last decade studied. The perinatal mortality rate was 30.7% and was very similar during the 2 decades. Conclusion HELLP syndrome is a frequent diagnosis (92.8%) in hepatic hemorrhage/rupture. The major reduction in maternal mortality rate was probably associated with advances in resuscitation, intensive-care medicine, and surgical intervention, including liver transplantation and arterial embolization.
Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, ...outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel‐treated intermediate and poor metabolizers (24 of 125 19.2%) versus patients treated with clopidogrel without a no function allele (43 of 442 9.7%; 35.1 versus 15.9 events per 100 person‐years; adjusted hazard ratio, 2.00 95% CI, 1.20–3.33, P =0.008). Bleeding event rates were low overall (23 of 567 4.1%) and did not differ among the metabolizer groups. Conclusions Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real‐world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype‐guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Aims
Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells ...and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF).
Methods and results
Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P < 0.05). Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose‐dependent manner and markedly decreased the expression of IL‐1β, IL‐6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL‐1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2.
Conclusions
SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.
Background Early generation drug-eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium-dependent ...vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device-related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable-polymer everolimus-eluting Xience (n=44), bioresorbable-polymer sirolimus-eluting Orsiro (n=35), polymer-free biolimus-eluting Biofreedom (n=24), bioactive endothelial-progenitor cell-capturing sirolimus-eluting Combo DES (n=25), polymer-based everolimus-eluting Absorb (n=44), and Mg-based sirolimus-eluting Magmaris BRS (n=34) underwent endothelium-dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow-up. Crude vasomotor responses of distal segments to low-dose acetylcholine (10
mol/L) were different between groups: bioresorbablepolymer DEShad the worst (-8.4%±12.6%) and durable-polymer DES had the most physiologic (-0.4%±11.8%;
=0.014). High-dose acetylcholine (10
mol/L) showed similar responses between groups (ranging from -10.8%±11.6% to -18.1%±15.4%;
=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable-polymer DES) to 2.5%±4.5% (bioactive DES;
=0.056). In multivariate models, endothelium-dependent vasomotor response was associated with age, bioresorbable-polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low-dose and 68.9% with high-dose acetylcholine, without differences between groups. Conclusions At follow-up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.
Abstract Objective To review case reports of retinal detachment in women with pre-eclampsia/eclampsia. Methods Medline was searched for case reports of retinal detachment associated with ...pre-eclampsia/eclampsia. Articles written in English, Spanish, or Portuguese and published between 1990 and 2010 were reviewed. Results A total of 28 cases of retinal detachment were identified; 15 were associated with severe pre-eclampsia (3 of these probably had hemolysis, elevated liver enzymes, and low platelets HELLP syndrome), 9 with HELLP syndrome, 2 with eclampsia, and 2 with both HELLP syndrome and eclampsia. The majority (60%) of women were nulliparous, 4 had abruptio placentae, and cesarean delivery was performed in 76%. Retinal detachment was bilateral in 89% and associated with delivery of the fetus in 96%; 69% were diagnosed postpartum. Within 2–12 weeks postpartum, all patients had complete recovery of vision with clinical management. Conclusion Retinal detachment in pre-eclampsia/eclampsia might be associated with HELLP syndrome, indicating that microangiophatic hemolysis might have a role in the pathophysiology of retinal detachment. Its occurrence might not be correlated with the severity of pre-eclampsia because pre-eclampsia is a constellation of signs and symptoms (persistent vasospasms with hemolysis and hypoalbuminemia) rather than simply being hypertension.
The aim of the study was to develop a scoring model to evaluate the quality of bioresorbable vascular scaffold (BVS) implantation and determine the model's usefulness in predicting adverse cardiac ...events.
The implantation technique and clinical outcomes of 1,736 lesions treated with BVS were analysed using the GHOST-EU registry. Predilation, scaffold sizing, and post-dilation (PSP) were scored according to the hazard model derived from the weight of these variables. The primary endpoint was a one-year device-oriented composite endpoint (DoCE) composed of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation. Definite/probable scaffold thrombosis was also evaluated as defined by the Academic Research Consortium. The PSP model performance was evaluated by internal validation. Predilation, correct scaffold sizing, and post-dilation with a non-compliant balloon were performed in 95.7%, 50.2%, and 26.2% of the cases and scored 0.63, 1.96 and 1.93 points, respectively, in the PSP-1 model. PSP-1 was an independent predictor of one-year DoCE (HR 0.75, 95% CI: 0.61-0.93; p=0.007), but with poor calibration and discrimination (AUC 0.611, 95% CI: 0.545-0.677). No patient with a maximum PSP-1 score had scaffold thrombosis, compared to those with a non-maximum PSP-1 score (0% vs. 2.3%; p=0.095).
At one-year follow-up, the PSP-1 score was an independent predictor of DoCE. External validation and prospective studies are needed to determine the clinical usefulness of this score.
To determine long-term survival of patients after cardiac arrest undergoing emergent coronary angiography and therapeutic hypothermia.
We analysed data from patients treated within the regional STEMI ...Network from January 2015 to December 2020. The primary endpoint was all-cause mortality at median follow-up. Secondary endpoints were periprocedural complications (arrhythmias, pulmonary edema, cardiogenic shock, mechanical complication, stent thrombosis, reinfarction, bleeding) and 6-month all-cause death. A landmark analysis was performed, studying two time periods; 0–6 months and beyond 6 months.
From a total of 24,125 patients in the regional STEMI network, 494 patients who suffered from cardiac arrest were included and divided into two groups: treated with (n = 119) and without therapeutic hypothermia (n = 375). At median follow−up (16.0 0.2–33.3 months), there was no difference in the adjusted mortality rate between groups (51.3 % with hypothermia vs 48.0 % without hypothermia; HRadj1.08 95%CI 0.77–1.53; p = 0.659). There was a higher frequency of bleeding in the hypothermia group (6.7 % vs 1.1 %; ORadj 7.99 95%CI 2.05–31.2; p = 0.002), without difference for the rest of periprocedural complications. At 6-month follow−up, adjusted all-cause mortality rate was similar between groups (46.2 % with hypothermia vs 44.5 % without hypothermia; HRadj1.02 95%CI 0.71–1.47; p = 0.900). Also, no differences were observed in the adjusted mortality rate between 6 months and median follow−up (9.4 % with hypothermia vs 6.3 % without hypothermia; HRadj2.02 95%CI 0.69–5.92; p = 0.200).
In a large cohort of patients with cardiac arrest within a regional STEMI network, those treated with therapeutic hypothermia did not improve long−term survival compared to those without hypothermia.
•In patients withcardiac arrest with suspected STEMI, hypothermia did not improve long−term survival.•In a landmark analysis, hypothermia was not associated with better survival between 0 and 6 months or beyond.•There were no prespecified subgroups in whom hypothermia was associated with better long-term survival.•The maintained low survival rates after cardiac arrest should lead to a investigation of efficient therapeutic interventions.
PDF
