Adv Exp Med Biol
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Cardiovascular disease remains the leading cause of morbidity and mortality for both women and men. Emerging evidence supports that ischemic heart disease (IHD) may manifest differently in women and men, in ways ranging from the clinical presentation, diagnosis, and management of disease to the basic biology and biomechanics of cardiomyocyte function and the coronary circulation. Women consistently present with a higher burden of symptoms and comorbidities as compared with men and experience worse outcomes. ⋯ When present, these processes increase cardiovascular risk in both women and men but may constitute an especially malignant phenotype in a subset of severely affected women, with implications for the management of not only CAD but also heart failure with preserved ejection fraction. This represents a state-of-the-art review of sex differences in the coronary system, with an eye toward how diverse pathophysiological processes may contribute to IHD phenotypes prevalent in women and men. Beyond providing women and men with equitable optimal care according to current paradigms, understanding the pathophysiology of IHD beyond a conventional focus on obstructive CAD is needed to address what is likely a combination of biological as well as environmental determinants of their prognosis.
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The use of direct acting vasodilators (the combination of hydralazine and isosorbide dinitrate -Hy+ISDN-) in heart failure with reduced ejection fraction (HFrEF) is supported by evidence, but rarely used. However, treatment with Hy+ISDN is guideline-recommended for HFrEF patients who cannot receive either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers due to intolerance or contraindication, and in self-identified African-American HFrEF patients who are symptomatic despite optimal neurohumoral therapy. The Hy+ISDN combination has arterial and venous vasodilating properties. ⋯ Furthermore, Hy+ISDN combination has antioxidant property, it affects endothelial dysfunction beneficially and improves NO bioavailability. Because of these benefits, this combination can improve the signs and symptoms of heart failure, exercise capacity and quality of life, and, most importantly, reduce morbidity and mortality in well-defined subgroups of HFrEF patients. Accordingly, this therapeutic option can in many cases play an essential role in the treatment of HFrEF.
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Globally, there are 18-million individuals living with heart failure, a disease that is responsible for 12-15 million office visits and 6.5 million inpatient hospitalizations each year. As HF becomes advanced or end-stage, patients often live in a cycle of frequent transitions between care settings, and with unmet needs, including distress from inadequately managed symptoms. Prognostication in patients with heart failure can be challenging due to the unpredictable exacerbating-remitting illness trajectory that is associated with this progressive disease. ⋯ Palliative care can help alleviate these symptoms and also facilitate conversations about decision making surrounding resuscitation status and use or deactivation of medical devices, such as an implantable-cardioverter-defibrillator (ICD). Clinical practice guidelines from the American College of Cardiology and American Heart Association report that aggressive life-sustaining treatments and therapies should not be utilized in patients with advanced heart failure who have refractory symptoms that are not responding to medical therapy. The focus of care should switch to controlling symptoms, reducing hospital admissions and improving health-related quality of life, which can be supported by the incorporation of palliative care into the treatment plan.
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Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system play crucial roles in heart failure with reduced ejection fraction (HFrEF). Clinical trials provide strong evidence of prognostic benefits for combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and β-blocker in the treatment of HFrEF. Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and an alternative for patients who are intolerant to ACEI. ⋯ In contrast to the evidence in HFrEF, clinical value of combination therapy with RAAS inhibitors and β-blocker is not well established in HF with preserved EF (HFpEF). The heterogeneity of diagnostic criteria and baseline characteristics of HFpEF need further evidence for the combination therapy. However, a recent clinical trial of LCZ696 showed promising results in reducing NT-proBNP in patients with HFpEF.
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Observational Study
Neutrophil Gelatinase-Associated Lipocalin: A Biomarker for Early Diagnosis of Urinary Tract Infections in Infants.
Early diagnosis of urinary tract infection (UTI) is challenging in infants due to unspecific symptoms, difficulty in urine collection and possible contamination. The aim of this study was to assesses the usefulness of serum and urine neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) in the diagnosis of febrile and non-febrile UTI in infants. This prospective observational study enrolled 66 infants with the first episode of UTI and 18 healthy controls. ⋯ The receiver operating curves (ROC) demonstrate that the optimum cut-off of 76.2 ng/ml for sNGAL (sensitivity 92.9%, specificity 94.4%, and the area under the curve (AUC) of 0.98) and of 42.2 ng/ml for uNGAL (sensitivity 73.8%, specificity 72.2%, and AUC of 0.76) for diagnosing febrile UTI and 39.0 ng/ml for sNGAL (sensitivity 83.3%, specificity 55.6%, and AUC of 0.70) for diagnosing non-febrile UTI. In conclusion, serum NGAL is an excellent marker for the early diagnosis of febrile UTI, with sensitivity and specificity higher than those of urine NGAL. Diagnostic sensitivity of serum NGAL is smaller in non-febrile infants suffering from UTI, and urine NGAL is not useful for this purpose at all.