RESUMO
Heart failure is a common entity encountered in healthcare with a vast socioeconomic impact. Recent advances in pharmacotherapy have led to the development of novel therapies with mortality benefits, improvement in heart failure symptoms and hospitalizations. This article is intended to explore those newer pharmacotherapies and summarize the evidence behind guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). It has been several years since any significant advances in pharmacotherapy of heart failure have resulted in survival benefit. Angiotensin-neprilysin inhibitors through the PARADIGM-HF and PIONEER-HF trials have shown mortality benefits and a reduction in heart failure hospitalizations and are considered landmark trials in heart failure. Vericiguat is an oral guanylate cyclase stimulator that through the recent VICTORIA trial showed a 10% relative difference in death from cardiovascular cause or hospitalization for heart failure. The sodium-glucose transport protein 2 (SGLT2) inhibitors are another class of medications that have shown promise in the treatment of patients with HFrEF and diabetes mellitus. The CANVAS and EMPA-REG OUTCOME trials showed the potential benefit of SGLT2 inhibitors on cardiovascular mortality, DECLARE-TIMI 58 trial showed that treatment with dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure to a greater extent in patients with reduced ejection fraction (EF). Although novel pharmacotherapy is the current focus of intense research, there have been numerous studies on potential benefit of iron supplementation in ferropenic patients with heart failure. Another rapidly expanding area of research in the realm of heart failure is precision medicine and its impact on the development, progression, and treatment of heart failure. The field of heart failure is dynamic and with the influx of data from recent and ongoing trials, newer therapies with morbidity and mortality benefits in HFrEF are now available, nonetheless, much work is still needed.
RESUMO
Coronary artery disease (CAD) is prevalent throughout the world, with a significant impact on global health. There is a vast collection of data in the medical literature relating to the topic of dual antiplatelet therapy (DAPT) in patients considered to be at high cardiovascular (CV) risk. In order to perform a narrative review of literature regarding the use of DAPT in patients with high CV risk, PubMed, Google Scholar and Embase were searched for English-language articles from 1985 to December 2020 by using the medical subject heading terms and keywords 'antiplatelet therapy' and 'high-risk cardiovascular disease', alone or in combination. Both authors critically reviewed the design, population characteristics and results of the selected studies. The topic of DAPT in patients with high CV risk is fluid and constantly evolving. The landmark trials of CURE, TRITON-TIMI 38 and PLATO provided evidence for the optimal use of DAPT in patients after acute coronary syndrome, while the CHARISMA and MATCH trials provided guidance for clinicians for their use in patients with stable coronary artery disease. The American College of Cardiology/American Heart Association focused update, published in 2016, and the European Society of Cardiology guidelines, published in 2017, were developed to provide guidance to clinicians based on the available data at the time to be able to choose the appropriate DAPT strategy that would provide patients with the maximum clinical benefit. The management of DAPT in patients with high CV risk is a challenging task, with new data on the subject constantly being reported. Balancing ischaemic benefit with potential bleeding complications adds to the complexity of managing DAPT in these patients. With all the available data and current clinical guidelines, patients deemed at high CV risk should be considered for DAPT, taking into account individual risk:benefit ratio. In most individuals with high CV risk, the net clinical benefit favours the use of DAPT.
RESUMO
The hydration of glycine is investigated by comparing the structures of bare glycine to its hydrated complexes, glycine.H(2)O and glycine.(H(2)O)(2). The Fourier transform infrared spectra of glycine and glycine.water complexes, embedded in Ar matrices at 12 K, have been recorded and the results were compared to density functional theory (DFT) calculations. An initial comparison of the experimental spectra was made to the harmonic infrared spectra of putative structures calculated at the MPW1PW91/6-311++G(d,p) level of theory. The results suggest that bare glycine adopts a C(s) symmetry structure (G-1), where the hydrogens of the amino NH(2) hydrogen-bond intramolecularly with the carboxylic acid C horizontal lineO oxygen. Also observed as minor constituents are the next two lowest-energy structures, one in which the carboxylic acid (O-)H group hydrogen-bonds to the amino NH(2) group (G-2), and the other where intramolecular hydrogen bonding occurs between the NH(2) and the carboxylic acid O(-H) groups (G-3). The abundances of these structures are estimated at 84%, 9% and 8%, respectively. The least favored structure, G-3, can be eliminated by annealing the matrix to 35 K. Addition of the first water molecule to G-1 takes place at the carboxylic acid group, with simultaneous hydrogen bonding of the water molecule to the carboxylic acid (C=)O and (O-)H. The results are consistent with the predominance of this structure, although there is evidence for a small amount of a hydrated G-2 structure. Addition of the second water molecule is less definitive, as only a small number of intense infrared modes can be unambiguously assigned to glycine.(H(2)O)(2). Anharmonic frequency calculations based on second-order vibrational perturbation theory have also been carried out. It is shown that such calculations can generate improved estimates (i.e., approximately 2%) of the experimental frequencies for glycine and glycine.H(2)O, provided that the potential energy surfaces are modeled with high-level ab initio approaches (MP2/aug-cc-pVDZ).
