The purpose of this paper is to describe all available evidence on the distinctive features of a group of 4 life-threatening acute aortic pathologies gathered under the name of acute aortic syndrome ...(AAS). The epidemiology, diagnostic strategy, and management of these patients has been updated. The authors propose a new and simple diagnostic algorithm to support clinical decision making in cases of suspected AAS, thereby minimizing diagnostic delays, misdiagnoses, and unnecessary advanced imaging. AAS-related entities are reviewed, and a guideline to avoid imaging misinterpretation is provided. Centralization of patients with AAS in high-volume centers with high-volume surgeons is key to improving clinical outcomes. Thus, the role of multidisciplinary teams, an "aorta code" (streamlined emergent care pathway), and aortic centers in the management of these patients is boosted. A tailored patient treatment approach for each of these acute aortic entities is needed, and as such has been summarized. Finally, a set of prevention measures against AAS is discussed.
Several studies have demonstrated the benefits of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis, but the presence of persistent fibrosis and myocardial hypertrophy ...has been related to worse prognosis.
The aim of this study was to explore the potential benefits of renin-angiotensin system (RAS) inhibitors on left ventricular remodeling and major clinical outcomes following successful transcatheter aortic valve replacement (TAVR).
Patients from 10 institutions with severe aortic stenosis who underwent TAVR between August 2007 and August 2017 were included. All baseline data were prospectively recorded, and pre-specified follow-up was performed. Doses and types of RAS inhibitors at discharge were recorded, and matched comparison according to their prescription at discharge was performed.
A total of 2,785 patients were included. Patients treated with RAS inhibitors (n = 1,622) presented similar surgical risk scores but a higher rate of all cardiovascular risk factors, coronary disease, and myocardial infarction. After adjustment for these baseline differences, reduction of left ventricular volumes and hypertrophy was greater and cardiovascular mortality at 3-year follow-up was lower (odds ratio: 0.59; 95% confidence interval: 0.41 to 0.87; p = 0.007) in patients treated with RAS inhibitors. Moreover, RAS inhibitors demonstrated a global cardiovascular protective effect with significantly lower rates of new-onset atrial fibrillation, cerebrovascular events, and readmissions.
Post-TAVR RAS inhibitors are associated with lower cardiac mortality at 3-year follow-up and offer a global cardiovascular protective effect that might be partially explained by a positive left ventricular remodeling. An ongoing randomized trial will help confirm these hypothesis-generating findings. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation RASTAVI; NCT03201185)
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Little information exists regarding population-based epidemiological changes in infective endocarditis (IE) in Europe.
This study sought to analyze temporal trends in IE in Spain from 2003 to 2014.
...This retrospective, population-based, temporal trend study analyzed the incidence, epidemiological and clinical characteristics, and outcome of all patients discharged from hospitals included in the Spanish National Health System with a diagnosis of IE, from January 2003 to December 2014.
Overall, 16,867 episodes of IE were identified during the study period, 66.3% in men. The rate of IE significantly increased, from 2.72 in 2003 to 3.49 per 100,000 person-years in 2014, and this rise was higher among older adults. The most frequent microorganisms were staphylococci (28.7%), followed by streptococci (20.4%) and enterococci (13.1%). Twenty-three percent of patients underwent cardiac surgery. The in-hospital mortality rate was 20.4%. Throughout the study period, the proportion of patients with previously known heart valve disease and diabetes mellitus significantly increased, whereas the prevalence of intravenous drug use decreased. Regarding microorganisms, Staphylococcus aureus and streptococci slightly declined, whereas coagulase-negative staphylococci and enterococci consistently increased over the years. In-hospital complications and cardiac surgery rates significantly increased across the years. The risk-adjusted in-hospital mortality rate diminished (0.2% per year) during the study period.
The incidence of IE episodes significantly increased over the decade of the study period, particularly among older adults. Relevant changes in clinical and microbiological profile included older patients with more comorbidity and a rise in enterococci and coagulase-negative staphylococcal infections. Adjusted mortality rates slightly declined over the study period.
OBJECTIVE—Calcific aortic valve disease is the most prevalent valvulopathy in Western countries. An unanticipated pathogenetic clue involving IFN (interferon) was disclosed by the finding of ...constitutive type I IFN activity associated with aortic valve calcification in children with the atypical Singleton-Merten syndrome. On this basis, the role of type I IFN on inflammation and calcification in human aortic valve interstitial cells (AVIC) was examined.
APPROACH AND RESULTS—IFN-α was weakly proinflammatory but potentiated lipopolysaccharide-mediated activation of NF (nuclear factor)-κB and the ensuing induction of proinflammatory molecules in human AVIC. Stimulation with IFN-α and in combination with lipopolysaccharide promoted osteoblast-like differentiation characterized by increased osteoblastic gene expression, BMP (bone morphogenetic protein)-2 secretion, and ectopic phosphatase activity. Sex differences were observed. Likewise, IFN-α treatment of human AVICs in osteogenic medium resulted in increased formation of calcific nodules. Strikingly, IFN-α–mediated calcification was significantly higher in AVICs from males, and was blocked by tofacitinib, a JAK (Janus kinase) inhibitor, and by a BMP antagonist. A female-specific protective mechanism involving the activation of PI3K-Akt (protein kinase B) pathways and cell survival was disclosed. Females exhibited higher levels of BCL2 in valve cells and tissues and lower annexin V staining on cell stimulation.
CONCLUSIONS—IFN-α acts as a proinflammatory and pro-osteogenic cytokine in AVICs, its effects being potentiated by lipopolysaccharide. Results also uncovered sex differences with lower responses in female AVICs and sex-specific mechanisms involving apoptosis. Data point to JAK/STAT (signal transducer and activator of transcription) system as a potential therapeutic target for calcific aortic valve disease.
RATIONALE:Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory and regenerative properties with a robust safety profile in large animal models of heart disease.
...OBJECTIVE:To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment elevation myocardial infarction (STEMI).
METHODS AND RESULTS:CAREMI was a phase I/II multicenter, randomized, double-blind, placebocontrolled trial in patients with STEMI, LVEF ≤ 45% and infarct size ≥ 25% of left ventricular (LV) mass by cardiac magnetic resonance (MR), who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at day 5-7. The primary endpoint was safety and included all-cause death and major adverse cardiac events at 30 days (MACEall-cause death, reinfarction, hospitalization due to heart failure, sustained ventricular tachycardia, ventricular fibrillation and stroke). Secondary safety endpoints included MACE at 6 and 12 months, adverse events (AE) and immunological surveillance. Secondary exploratory efficacy endpoints were changes in infarct size (% LV mass) and indices of ventricular remodeling by MR at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or MACE were reported at 12 months. One severe AE in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor specific antibodies in 2 patients. No immune-related AE were found and no differences between groups were observed in MR-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95%CI -6.5 to 1.9%).
CONCLUSIONS:Allogeneic cardiac stem cells can be safely administered in STEMI patients with LV dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting.
CLINICAL TRIAL REGISTRATION:NCT 02439398.
Calcific aortic valve disease (CAVD) is an athero-inflammatory process. Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and ...tumor necrosis factor (TNF)-α. Our goal was investigating IFNs’ effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells. The endothelial phenotype was analyzed by Western blot, qPCR, ELISA, monocyte adhesion, and migration assays. In mixed VEC populations, IFNs promoted the activation of signal transducers and activators of transcription-1 and nuclear factor-κB, and the subsequent up-regulation of pro-inflammatory molecules. Side-specific VEC were activated with IFN-γ and TNF-α in an orbital shaker flow system. TNF-α, but not IFN-γ, induced hypoxia-inducible factor (HIF)-1α stabilization or endothelial nitric oxide synthase downregulation. Additionally, IFN-γ inhibited TNF-α–induced migration of aVEC. Also, IFN-γ triggered cytokine secretion and adhesion molecule expression in aVEC and vVEC. Finally, aVEC were more prone to cytokine-mediated monocyte adhesion under multiaxial flow conditions as compared with uniaxial flow. In conclusion, IFNs promote inflammation and reduce TNF-α–mediated migration in human VEC. Moreover, monocyte adhesion was higher in inflamed aVEC sheared under multiaxial flow, which may be relevant to understanding the initial stages of CAVD.
Inflammation, the primary response of innate immunity, is essential to initiate the calcification process underlying calcific aortic valve disease (CAVD), the most prevalent valvulopathy in Western ...countries. The pathogenesis of CAVD is multifactorial and includes inflammation, hemodynamic factors, fibrosis, and active calcification. In the development of CAVD, both innate and adaptive immune responses are activated, and accumulating evidences show the central role of inflammation in the initiation and propagation phases of the disease, being the function of Toll-like receptors (TLR) particularly relevant. These receptors act as sentinels of the innate immune system by recognizing pattern molecules from both pathogens and host-derived molecules released after tissue damage. TLR mediate inflammation via NF-κB routes within and beyond the immune system, and play a crucial role in the control of infection and the maintenance of tissue homeostasis. This review outlines the current notions about the association between TLR signaling and the ensuing development of inflammation and fibrocalcific remodeling in the pathogenesis of CAVD. Recent data provide new insights into the inflammatory and osteogenic responses underlying the disease and further support the hypothesis that inflammation plays a mechanistic role in the initiation and progression of CAVD. These findings make TLR signaling a potential target for therapeutic intervention in CAVD.
Ramipril in High-Risk Patients With COVID-19 Amat-Santos, Ignacio J.; Santos-Martinez, Sandra; López-Otero, Diego ...
Journal of the American College of Cardiology,
07/2020, Letnik:
76, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting ...enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors.
This study analyzed whether RAAS inhibitors modify the risk for COVID-19.
The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril’s impact on COVID-19 risk in this vulnerable population.
As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039).
In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation RASTAVI; NCT03201185)
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The "3 noes right-sided infective endocarditis" (3no-RSIE: no left-sided, no drug users, no cardiac devices) was first described more than a decade ago. We describe the largest series to date to ...characterize its clinical, microbiological, echocardiographic and prognostic profile. Eight tertiary centers with surgical facilities participated in the study. Patients with right-sided endocarditis without left sided involvement, absence of drug use history and no intracardiac electronic devices were retrospectively included in a multipurpose database. A total of 53 variables were analyzed in every patient. We performed a univariate analysis of in-hospital mortality to determine variables associated with worse prognosis. the study was comprised of 100 patients (mean age 54.1 ± 20 years, 65% male) with definite 3no-RSIE were included (selected from a total of 598 patients with RSIE of all the series, which entails a 16.7% of 3no-RSIE). Most of the episodes were community-acquired (72%), congenital cardiopathies were frequent (32% of the group of patients with previous known predisposing heart disease) and fever was the main manifestation at admission (85%). The microbiological profile was led by Staphylococci spp (52%). Vegetations were detected in 94% of the patients. Global in-hospital mortality was 19% (5.7% in patients operated and 26% in patients who received only medical treatment, P < .001). Non-community acquired infection, diabetes mellitus, right heart failure, septic shock and acute renal failure were more common in patients who died. the clinical profile of 3no-RSIE is closer to other types of RSIE than to LSIE, but mortality is higher than that reported on for other types of RSIE. Surgery may play an important role in improving outcome.
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