Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode.

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

Evidence-based Management of Left Main Coronary Artery Disease.

Left main coronary artery disease (LMCAD) is associated with high morbidity and mortality due to the large myocardial mass at risk. Although medical treatment may be an option in selected low-risk patients, revascularisation is recommended to improve survival in the majority of patients presenting with a significant left main stenosis. In the past decade, multiple randomised clinical trials and meta-analyses have compared coronary artery bypass grafting surgery (CABG) versus percutaneous coronary intervention (PCI), finding controversial results. The strategy for LMCAD revascularisation is still challenging. Coronary anatomy complexity, clinical features and patient preferences are key elements to be considered by the heart team. The current guidelines define CABG as standard therapy, but the continuous improvements in PCI techniques, the use of intracoronary imaging and functional assessment make PCI a feasible alternative in selected patients, particularly in those with comorbidities and contraindications to CABG. This review analyses the most important studies comparing CABG versus PCI in patients with LMCAD.

World Heart Federation Roadmap on Atrial Fibrillation - A 2020 Update.

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world's population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great.

Improvement in Atrial Fibrillation-Related Symptoms After Cardioversion: Role of NYHA Functional Class and Maintenance of Sinus Rhythm.

BACKGROUND: The European Heart Rhythm Association (EHRA) score is a proven and validated tool for assessing the symptoms of atrial fibrillation (AF). Little is known about the variables related to this score and how it changes after cardioversion. METHODS: We analyzed 744 patients undergoing elective cardioversion in whom AF-related symptoms were assessed at baseline and after 6 months of follow-up using the EHRA score. We assessed the association between the EHRA score and other clinical and echocardiographic variables at baseline and after 6 months of follow-up. RESULTS: At 6 months of follow-up, we observed a reduction in the EHRA score in 50% and worsening in 2.8% of patients who remained in sinus rhythm (SR) compared with 34.6% and 11.3%, respectively, of patients with AF episodes (p<0.0001). Patients who maintained SR at 6 months were less symptomatic than those with AF (EHRA score 1.13 ± 0.35 vs 1.42 ± 0.59; p<0.0001). The independent predictors for reduction in the EHRA score after cardioversion were NYHA ≥II at baseline and maintenance of SR (p<0.0001). CONCLUSION: The greatest improvement in AF-related symptoms was in patients who remained in SR at 6 months after cardioversion and in patients with worse NYHA functional class at baseline.

Impact of prescription patterns of antithrombotic treatment on atrial fibrillation-related ischemic stroke.

OBJECTIVE: To analyze the temporal trends of atrial fibrillation (AF)-related ischemic stroke (IS) and their relationship with the prescription patterns of antithrombotic treatment from 2013 to 2019 in the Health Assistance Area of a regional hospital. METHODS: First, a retrospective ecological study of aggregate data to analyze the annual incidence of IS between 2013 and 2019 was performed. Second, we selected those patients diagnosed with AF between 2013 and 2019 and performed a retrospective longitudinal study to assess the role of antithrombotic therapy in the development of AF-related IS. RESULTS: During this period, whereas the annual incidence of IS remained stable (from 1.3 in 2013 to 1.2 cases per 1000 inhabitants in 2019; adjusted P for trend .829), the annual incidence of AF-related IS decreased over time (from 23.8 to 18.8 cases per 1000 inhabitants, respectively; adjusted P for trend .001). Among AF patients, the use of direct oral anticoagulants increased from 5.5% to 46.8%, while the prescription of antiplatelets and vitamin K antagonists decreased from 21.9% to 6.0% and from 63.8% to 36.1%, respectively. Overall, the use of oral anticoagulants increased from 69.3% to 82.9%; p < .001. Patients under antiplatelet agents had a higher probability of presenting IS than those patients taking oral anticoagulants, either vitamin K antagonists or direct oral anticoagulants (adjusted OR 1.89; 95% CI 1.52-2.37; p < .001). CONCLUSIONS: The prescription of oral anticoagulants, particularly direct oral anticoagulants, has increased from 2013 to 2019 in our Health Assistance Area. This increase might partially explain the reduction in AF-related IS.

Coronavirus Disease 2019 and Cardiac Arrhythmias.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a very contagious virus, has led to the coronavirus disease 2019 (COVID-19) pandemic. The clinical manifestations of this virus in humans vary widely, from asymptomatic to severe, with diverse symptomatology and even death. The substantial transmission from asymptomatic people has facilitated the widespread transmission of SARS-CoV-2, hampering public health initiatives to identify and isolate infected people during the pre-symptomatic contagious period. COVID-19 is associated with cardiac complications that can progress from mild to life-threatening. The aim of this article is to analyse the present knowledge of COVID-19 and cardiac involvement, the development of arrhythmia risk and its treatment.

Anemia and iron deficiency in heart failure: a review of echocardiographic features.

Anemia and iron deficiency are often associated with heart failure, influencing the symptoms and prognosis. Correction of anemia and iron deficiency improves functional capacity and decreases hospitalizations. Many studies have analyzed echocardiographic parameters in iron deficiency and anemia and their evolution after iron treatment; however, the heterogeneity of the results makes it difficult to draw conclusions. The aim of this paper is to review the echocardiographic parameters during anemia and iron deficiency, and their evolution after treatment. Available data suggest that they lead to ventricular and atrial remodeling, a decrease in ventricular contractility, and an alteration of ventricular relaxation, although in heart failure with preserved ejection fraction these changes are not significant. Anemia and iron deficiency also increase systolic pulmonary artery pressure. There is consistent evidence that correction of these comorbidities leads to a reduction in preload and left ventricular cavity dimensions, an improvement in diastolic and load-independent ventricular systolic function parameters, and a decrease in systolic pulmonary artery pressure. However, the evidence is less consistent about the changes produced in ventricular hypertrophy, load-dependent systolic function parameters, and E-wave. Generally, anemia and iron deficiency affect the echocardiographic findings, and correcting these conditions often results in improvement in the affected echocardiographic parameters.

Impact of an integral assistance model between primary care and cardiology on the management of patients with ischemic heart disease or atrial fibrillation.

AIM: To analyze the impact of implementing a program integrating cardiology and primary care in clinical practice. METHODS: In the integrated care model, every cardiologist was assigned to each primary care center. RESULTS & CONCLUSION: The implementation of the new care model was associated with a significant reduction of 31.2% in requests of first visits. In addition, the delay to the cardiologist consultation significantly decreased by 54.5% for the first visits, and by 57.1% for the follow-up visits. The proportion of patients that achieved recommended low density lipoprotein-cholesterol goals significantly increased from 20.8 to 29.6%. The proportion of patients submitted to anticoagulant therapy significantly increased from 69.3 to 74.2%, as well as the proportion of patients taking direct oral anticoagulants (from 7.9 to 28.4%).

The local microenvironment limits the regenerative potential of the mouse neonatal heart.

Neonatal mice have been shown to regenerate their hearts during a transient window of time of approximately 1 week after birth. However, experimental evidence for this phenomenon is not undisputed, because several laboratories have been unable to detect neonatal heart regeneration. We first confirmed that 1-day-old neonatal mice are indeed able to mount a robust regenerative response after heart amputation. We then found that this regenerative ability sharply declines within 48 hours, with hearts of 2-day-old mice responding to amputation with fibrosis, rather than regeneration. By comparing the global transcriptomes of 1- and 2-day-old mouse hearts, we found that most differentially expressed transcripts encode extracellular matrix components and structural constituents of the cytoskeleton. These results suggest that the stiffness of the local microenvironment, rather than cardiac cell-autonomous mechanisms, crucially determines the ability or inability of the heart to regenerate. Testing this hypothesis by pharmacologically decreasing the stiffness of the extracellular matrix in 3-day-old mice, we found that decreased matrix stiffness rescued the ability of mice to regenerate heart tissue after apical resection. Together, our results identify an unexpectedly restricted time window of regenerative competence in the mouse neonatal heart and open new avenues for promoting cardiac regeneration by local modification of the extracellular matrix stiffness.

Prevalence and incidence of Q-wave unrecognized myocardial infarction in general population: Diagnostic value of the electrocardiogram. The REGICOR study.

BACKGROUND: Diagnosis of unrecognized myocardial infarction (UMI) remains an open question in epidemiological and clinical studies, inhibiting effective secondary prevention of myocardial infarction. We aimed to determine the prevalence and incidence of Q-wave UMI in asymptomatic individuals aged 35 to 74years, and to ascertain the positive predictive value (PPV) of asymptomatic Q-wave to diagnose UMI. METHODS: Two population-based cross-sectional studies were conducted, in 2000 (with 10-year follow-up) and in 2005. A baseline electrocardiogram was obtained for each participant. Imaging techniques (echocardiography, cardiac magnetic resonance imaging, and myocardial perfusion single-photon emission computerized tomography) were used to confirm UMI in patients with asymptomatic Q-wave. RESULTS: The prevalence of confirmed Q-wave UMI in the 5580 participants was 0.18% (95% confidence interval [CI]: 0.10-0.33) and the incidence rate was 27.1 Q-wave UMI per 100,000person-years. The proportion of confirmed Q-wave UMI with respect to all prevalent MI was 8.1% (95% CI: 4.4-14.2). The PPV of asymptomatic Q-wave to diagnose Q-wave UMI was 29.2% (95% CI: 18.2-43.2%) overall, but much higher (75%, 95% CI: 40.9-92.9%) in participants with 10-year CHD risk ≥10%, compared to lower-risk participants. CONCLUSION: Opportunistic identification of asymptomatic Q-waves by routine electrocardiogram overestimates actual Q-wave UMI, which represents 8% to 13% of all myocardial infarction in the population aged 35 to 74years. This overestimation is particularly high in the population at low cardiovascular risk. In epidemiological studies and in clinical practice, diagnosis of a pathologic Q-wave in asymptomatic patients requires detailed analysis of imaging tests to confirm or rule out myocardial necrosis.

Expression of the T85A mutant of zebrafish aquaporin 3b improves post-thaw survival of cryopreserved early mammalian embryos.

While vitrification has become the method of choice for preservation of human oocytes and embryos, cryopreservation of complex tissues and of large yolk-containing cells, remains largely unsuccessful. One critical step in such instances is appropriate permeation while avoiding potentially toxic concentrations of cryoprotectants. Permeation of water and small non-charged solutes, such as those used as cryoprotectants, occurs largely through membrane channel proteins termed aquaporins (AQPs). Substitution of a Thr by an Ala residue in the pore-forming motif of the zebrafish (Dario rerio) Aqp3b paralog resulted in a mutant (DrAqp3b-T85A) that when expressed in Xenopus or porcine oocytes increased their permeability to ethylene glycol at pH 7.5 and 8.5. The main objective of this study was to test whether ectopic expression of DrAqp3b-T85A also conferred higher resistance to cryoinjury. For this, DrAqp3b-T85A + eGFP (reporter) cRNA, or eGFP cRNA alone, was microinjected into in vivo fertilized 1-cell mouse zygotes. Following culture to the 2-cell stage, appropriate membrane expression of DrAqp3b-T85A was confirmed by immunofluorescence microscopy using a primary specific antibody directed against the C-terminus of DrAqp3b. Microinjected 2-cell embryos were then cryopreserved using a fast-freezing rate and low concentration (1.5 M) of ethylene glycol in order to highlight any benefits from DrAqp3b-T85A expression. Notably, post-thaw survival rates were higher (P<0.05) for T85A-eGFP-injected than for -uninjected or eGFP-injected embryos (73±7.3 vs. 28±7.3 or 14±6.7, respectively). We propose that ectopic expression of mutant AQPs may provide an avenue to improve cryopreservation results of large cells and tissues in which current vitrification protocols yield low survival.

Using Direct Oral Anticoagulants in Patients with Atrial Fibrillation: Assessment, Monitoring and Treatment Reversal.

It is essential to prevent thromboembolic events in atrial fibrillation. The risks of thromboembolic and haemorrhagic events must be carefully assessed and weighed against one another, both in routine situations and in relation to invasive procedures. Vitamin K antagonists, until recently the first-line treatment for prophylaxis against thromboembolic events in patients with atrial fibrillation, have various drawbacks. Direct-acting oral anticoagulants overcome these limitations and are efficacious and safe. The recent developments of tests to monitor anticoagulant levels, and of target-specific reversal agents for these newer drugs, has facilitated their use in several situations, including emergencies. For these reasons, the European Society of Cardiology and other scientific societies now recommend direct-acting oral anticoagulants as first-line treatment for preventing thromboembolic events in atrial fibrillation.