Effectiveness of sacubitril-valsartan in patients with cancer therapy-related cardiac dysfunction: a systematic review of clinical and preclinical studies.

INTRODUCTION: Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. However, there are very limited data on the efficacy of sacubitril/valsartan in the prevention and treatment of cardiotoxicity. This systematic review aimed to evaluate the potential benefit of sacubitril/valsartan in patients with CTRCD. EVIDENCE ACQUISITION: The databases included MEDLINE, Embase, LILACS, Scopus and Cochrane Central up to January 20, 2022. All pre-clinical and clinical studies including observational studies (cohorts, case-control, cross-sectional and case reports) that used sacubitril/valsartan for prevention or treatment of CTRCD. The primary effectiveness endpoints was CTRCD, defined as a clinically significant change in left ventricular ejection fraction (LVEF) at the end of the follow-up. EVIDENCE SYNTHESIS: And after applying the eligibility criteria, 12 articles (9 in humans and 3 preclinical studies) were included in this systematic review. The 3 preclinical studies demonstrated beneficial effects in preventing, attenuating and/or delaying the onset of myocardial damage at the cellular level, ventricular dysfunction and remodeling. Regardind human studies, most of them were composed of case reports. The largest study consisted of a retrospective multicentric cohort with 64 patients. CONCLUSIONS: All clinical studies have demonstrated that used Sac/Val in human showed a significant increase in LVEF, and when reported, a reduction in left ventricular volume and NT-proBNP (or BNP). Randomized clinical trials are needed to confirm this hypothesis.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Rivaroxaban versus Warfarin in Patients with Mechanical Heart Valve: Rationale and Design of the RIWA Study.

INTRODUCTION: Mechanical heart valves (MHV) are extremely durable, but they require permanent use of anticoagulation to prevent thromboembolic events. The only approved therapeutic options are vitamin K antagonists (VKAs), such as warfarin. As a drug class, clinical management is difficult, therefore new alternatives need to be evaluated. METHODS: RIWA is a phase II/III, prospective, open-label, randomized, pilot study designed to investigate oral rivaroxaban 15 mg twice daily compared with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorrhagic) and systemic embolism in patients with MHV, from August 2018 to December 2019. Patients will undergo transesophageal echocardiography at the beginning and the end of the study (follow-up time 90 days). On an explanatory basis, all events will be analyzed, including stroke, peripheral systemic embolism, valve thrombosis, significant bleeding and death. DISCUSSION: Warfarin and similar VKAs are standard therapy for patients with an MHV. Even with the appropriate use of therapy, the incidence of thromboembolic events is high at 1-4% per year. Furthermore, bleeding risk is significant, ranging from 2 to 9% per year. The new frontier to be overcome in relation to use of the new oral anticoagulants is undoubtedly in patients with MHV. A significant portion of people with MHV worldwide will benefit if noninferiority of these new agents is confirmed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03566303. Recruitment Status: Recruiting. First Posted: 25 June 2018. Last Update Posted: 25 June 2018.

Usefulness and Safety of Rivaroxaban in Patients Following Isolated Mitral Valve Replacement With a Mechanical Prosthesis.

Rivaroxaban has previously been tested in experimental and animal models with encouraging results. We prospectively selected seven patients between May 2017 and January 2018 who underwent isolated mitral valve replacement with a mechanical prosthesis and had unstable INR control at least 3 months after surgery. An intervention of rivaroxaban 15mg was then administered twice daily for a period of 90days. No patient presented intracardiac thrombus, reversible ischemic neurological deficit, ischemic or hemorrhagic stroke, and hospitalization or death during 3 months of follow-up. Two patients eradicated the presence of spontaneous echo contrast. Mean and peak pressure gradients, peak velocity, effective orifice area, and PHT were similar before and after the intervention. In conclusion, the use of rivaroxaban for 90days in seven patients after replacement of mitral valve with the mechanical prosthesis did not present thromboembolic or bleeding events (NCT02894307).

Gender differences in ST-elevation myocardial infarction (STEMI) time delays: experience of a public health service in Salvador-Brazil.

BACKGROUND: Delays in attending to ST-elevation myocardial infarction (STEMI) are indicators or markers of quality of health services. Several records suggest gender disparity in cardiac care as a contributor to the increased mortality among women. METHODS: We prospectively enrolled all consecutive STEMI patients who were transferred to our hospital from January through December 2015. The following variables were analyzed: Symptom-to-Door Time (SDT); Time to First ECG (TECG); Transfer Time to Referring Center (TTRC); and Door-to-Cath lab time (DCT). RESULTS: Of the 133 patients, 85 (63.9%) were male and 45 (36%) female. The mean age and body mass index (BMI) between the male and female genders were 56.3 and 60.5 years for the first and 26 and 27.7 Kg/M2 for the second. Diabetes and low school education level were more prevalent in women than men, with statistical significance: 20 (48.8%) vs 18 (26.1%) with P = 0.01 and 26 (54.2%) vs 28 (32.9%) with P = 0.04, respectively. Regarding the times evaluated (SDT, TECG, TTRC and DCT), there was no statistically significant difference in relation to gender. STEMI Killip class I was more prevalent in males: 93 (86.1%) vs 12 (63.2%) cases with P = 0.01, and thrombolysis with a tendency towards the same direction: 17 (20%) vs 4 (8.3%) and P = 0.07. CONCLUSIONS: According to our results women with STEMI had significantly higher prevalence of diabetes and low school education level, as well as a higher proportion of complicated STEMI (Killip class ≥ II).

High-intensity interval training versus moderate-intensity continuous training on exercise capacity and quality of life in patients with coronary artery disease: A systematic review and meta-analysis.

Background Exercise is an effective strategy for reducing total and cardiovascular mortality in patients with coronary artery disease. However, it is not clear which modality is best. We performed a meta-analysis to investigate the effects of high-intensity interval versus moderate-intensity continuous training of coronary artery disease patients. Methods We searched MEDLINE, PEDro, LILACS, SciELO and the Cochrane Library (from the earliest date available to November 2016) for controlled trials that evaluated the effects of high-intensity interval versus moderate-intensity continuous training for coronary artery disease patients. Weighted mean differences and 95% confidence intervals were calculated, and heterogeneity was assessed using the I2 test. Results Twelve studies met the study criteria, including 609 patients. High-intensity interval training resulted in improvement in peak oxygen uptake weighted mean difference (1.3 ml/kg/min, 95% confidence interval: 0.6-1.9, n = 594) compared with moderate-intensity continuous training. No significant difference in physical, emotional, and social domain of quality of life was found for participants for participants in the high-intensity interval training group compared with the moderate-intensity continuous training group. Sub-analysis of three studies with isocaloric exercise training showed no significant difference in peak oxygen uptake weighted mean difference (0.4 ml/kg/min, 95% confidence interval: -0.1-0.9, n = 137) for participants in the high-intensity interval training group compared with moderate-intensity continuous training group. Conclusions High-intensity interval training may improve peak oxygen uptake and should be considered as a component of care of coronary artery disease patients. However, this superiority disappeared when isocaloric protocol is compared.

Estratégia antitrombótica nos três meses iniciais após implante de bioprótese valvar cardíaca / Antithrombotic strategy in the three first months following bioprosthetic heart valve implantation

A prótese valvar cardíaca indiscutivelmente melhora a qualidade de vida e a sobrevida de pacientes com valvulopatias severas, mas a necessidade de uma terapia antitrombótica para prevenir complicações tromboembólicas promove grandes desafios aos clínicos e aos seus pacientes. Dos artigos pesquisados, a maioria foi composta de séries retrospectivas de casos ou de coortes históricas extraídas de banco de dados. Os raros estudos randomizados publicados não apresentaram poder estatístico para se avaliar o desfecho primário de morte ou evento tromboembólico. Neste artigo, optamos por realizar uma revisão sistemática da literatura, tentando responder a seguinte pergunta: qual a melhor estratégia antitrombótica nos três primeiros meses após implante de bioprótese valvar cardíaca (mitral e aórtica)? Após aplicar-se os critérios de extração por dois revisores, encontrou-se 1968 referências, selecionando-se 31 artigos (foram excluídos artigos truncados, que combinaram prótese mecânica, ou sem follow-up). Baseado nesta revisão de literatura, observou-se um baixo nível de evidência para qualquer estratégia terapêutica antitrombótica avaliada. Sendo assim, é interessante utilizar aspirina 75 a 100 mg/dia como estratégia antitrombótica após implante de bioprótese na posição aórtica, independente da etiologia, para pacientes sem outros fatores de risco, como fibrilação atrial ou evento tromboembólico anterior. Já para o implante de bioprótese na posição mitral, o risco de embolia, apesar de baixo, é mais relevante do que na posição aórtica, segundo as séries publicadas e coortes retrospectivas composta principalmente de pacientes idosos não reumáticos.

Heart valve prosthesis unquestionably improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thromboembolic complications is a major challenge to clinicians and their patients. Of the articles analyzed, most were retrospective series of cases or historical cohorts obtained from the database. The few published randomized trials showed no statistical power to assess the primary outcome of death or thromboembolic event. In this article, we decided to perform a systematic literature review, in an attempt to answer the following question: what is the best antithrombotic strategy in the first three months after bioprosthetic heart valve implantation (mitral and aortic)? After two reviewers applying the extraction criteria, we found 1968 references, selecting 31 references (excluding papers truncated, which combined bioprosthesis with mechanical prosthesis, or without follow-up). Based on this literature review, there was a low level of evidence for any antithrombotic therapeutic strategy evaluated. It´s therefore interesting to use aspirin 75 to 100 mg / day as antithrombotic strategy after bioprosthesis replacement in the aortic position, regardless of etiology, for patients without other risk factors such as atrial fibrillation or previous thromboembolic event. In the mitral position, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts comprised mostly of elderly non-rheumatic patients.

Antithrombotic strategy in the three first months following bioprosthetic heart valve implantation.

Heart valve prosthesis unquestionably improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thromboembolic complications is a major challenge to clinicians and their patients. Of the articles analyzed, most were retrospective series of cases or historical cohorts obtained from the database. The few published randomized trials showed no statistical power to assess the primary outcome of death or thromboembolic event. In this article, we decided to perform a systematic literature review, in an attempt to answer the following question: what is the best antithrombotic strategy in the first three months after bioprosthetic heart valve implantation (mitral and aortic)? After two reviewers applying the extraction criteria, we found 1968 references, selecting 31 references (excluding papers truncated, which combined bioprosthesis with mechanical prosthesis, or without follow-up). Based on this literature review, there was a low level of evidence for any antithrombotic therapeutic strategy evaluated. It´s therefore interesting to use aspirin 75 to 100 mg / day as antithrombotic strategy after bioprosthesis replacement in the aortic position, regardless of etiology, for patients without other risk factors such as atrial fibrillation or previous thromboembolic event. In the mitral position, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts comprised mostly of elderly non-rheumatic patients.