Platypnea–orthodexia syndrome (POS) is often a challenging diagnostic problem. It is characterized by dyspnea that is accentuated by standing or sitting positions due to a marked fall in blood oxygen saturation, and instead is improved by assuming the lying position. In the present brief review, the authors address the pathophysiology of POS, and outline its clinical symptoms as well as the main modalities of diagnostic evaluation and possible therapeutic options. Moreover, some problems concerning much-debated issues and persistent uncertainties about the pathophysiology of POS are presented along with the description of the diagnostic and therapeutic resources currently available for this syndrome.

This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Objective:The association between chronic use of methotrexate and decreased risk of ischemic cardiovascular events (CVE) among patients with psoriatic or rheumatoid arthritis (RA) was investigated using a systematic review and meta-analysis.Methods:The studies should have recruited adults receiving methotrexate, followed up for at least one year. Moreover, studies should have reported “hard” cardiovascular endpoints, by evaluating the cardiovascular outcomes of the habitual users of the drug or of new users compared with patients with the same disease who had never used methotrexate. The outcome of interest was the overall pooled odds ratio (OR) of major adverse cardiovascular events, i.e., a composite of new- onset angina, acute coronary syndrome, need for percutaneous or surgical coronary revascularization, stroke, and cardiovascular death. The study was performed according to the PRISMA statement.Results:Seven observational studies, mostly engaging patients with RA, were included in the meta-analysis. The pooled odds ratio (OR) was 0.73 (95% CI=0.70- 0.77 p<0.001). When stratified meta-analysis models were assessed, the pooled OR was 0.80 (95% CI=0.66-0.97; p=0.022) for studies adjusting for clinical severity of RA. Furthermore, the OR was even more significant after adjustment for concomitant use of other drugs specific for RA (OR=0.71, 95% CI=0.67-0.75, p<0.001).Conclusion:Methotrexate at low doses, such those used for maintenance therapy of RA, predicted a decreased risk of CVE. Since methotrexate doesn’t interfere with blood lipids, platelet aggregation or insulin resistance, the protective association may originate from mechanisms other than those exerted by antiplatelet drugs or statins.

No abstract

HSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.

Background: The peak atrial longitudinal strain (PALS) is primarily an index of the reservoir function of atrial chambers. The conceptual basis exists to hypothesize that sacubitril/valsartan improves the expandability of atrial chambers in the reservoir phase of the atrial mechanical cycle, as a consequence of its effect of prolonging the half-life of natriuretic peptides. Therefore in this retrospective study we evaluated the repercussions of the administration of sacubitril/valsartan maintained for at least 12 months on the PALS. Methods: In our retrospective study a cohort of 40 patients treated with sacubitril/valsartan has been compared with a second cohort subjected to the conventional treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. A general criterion to be satisfied was the presence of at least one episode of atrial fibrillation (AF) in the history of the enrolled patients. The study population was composed of New York Heart Association (NYHA) class II/III chronic heart failure (CHF) patients, due to the fact that the treating physicians of the patients whose clinical records were used as source of data, complied with the international guidelines that have so far validated sacubitril/valsartan exclusively for the CHF therapy. The aims were to verify whether the 1-year administration of sacubitril/valsartan is effective in improving the PALS, and also ascertain whether the drug is associated with a decreased risk of AF relapses over a mean retrospective observation period of 12 months. Results: Sacubitril/valsartan cohort was proven to benefit from a significant increase in average values of PALS (median: 26.5%; in-terquartile range (IQR): 22%-30%), opposed to the much less pronounced increase in PALS found in the conventional therapy cohort (median: 22.5%; IQR: 18%-25.5%). Additionally, the comparison made by means of one-way analysis of variance regarding the mean changes of PALS values, outlined clearly that the sacubitril/valsartan users had an increase in PALS after 1 year of therapy significantly greater (P < 0.001) compared to the patients taking the conventional drugs. Moreover, a risk significantly higher of AF recurrences (P = 0.001) was identified in the conventional therapy group compared to the sacubitril/valsartan group during a 12-month retrospective observation period. Conclusions: In the present retrospective cohort study a higher increase of PALS has been shown in the cohort treated with sacubitril/valsartan. Moreover, a reduced risk of AF recurrences has been shown in the sacubitril/valsartan users compared to the patients with CHF subjected to conventional treatment.

BackgroundSeveral studies have compared the use of phosphodiesterase-5 (PDE5) inhibitors sildenafil or udenafil with the placebo in patients suffering from pulmonary hypertension (PH) due to left chronic heart failure (CHF), corresponding to group 2 (PH due to left heart disease) of the PH classification (according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The results of the use of PDE5 inhibitors in the PH due to left heart disease were inconsistent and heterogeneous. Therefore, we carried out a meta-analysis to assess the effect of PDE5 inhibitors in this clinical setting, i.e., patients with left CHF.MethodsA systematic search was conducted using the PubMed and Embase electronic archives. Studies had to be prospective randomized controlled trials (RCTs). In each of the RCTs admitted to meta-analysis, a comparison was made between a group of CHF patients taking a PDE5 inhibitor and a second group assigned a placebo. Studies were incorporated in the meta-analysis provided that they had sufficient information about two or more of the following clinical, ergospirometric or hemodynamic outcomes: the composite of all-cause death and hospitalization, adverse events, peak VO2, 6-min walking distance (6MWD), left ventricular ejection fraction (LVEF), E/e’ ratio, mean pulmonary arterial pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary vascular resistance (PVR).ResultsFourteen studies enrolling a total of 928 patients were incorporated in the meta-analysis. Among them,13 were RCTs and one was a subgroup analysis. Among patients with CHF with reduced left ventricular ejection fraction (HFREF, n = 555), a significant benefit was conferred by PDE5 inhibitors against the risk of the composite endpoint of death and hospitalizations (odds ratio (OR): 0.28; 95% confidence interval (CI): 0.10 - 0.74; P = 0.03). Furthermore, among HFREF patients, PDE5 inhibitors were associated with a significant improvement in peak VO2 (difference in means (MD): 3.76 mL/min/kg; 95% CI: 3.27 - 4.25) as well as in 6MWD (MD: 22.7 m; 95% CI: 8.19 - 37.21) and LVEF (MD: 4.30%; 95% CI: 2.18% to 6.42%). For patients with HFREF, PDE5 inhibitors caused a non-significant reduction in mPAP, while PASP was significantly reduced (MD: -11.52 mm Hg; 95% CI: -15.56 to -7.49; P < 0.001). By contrast, in the RCTs of patients with CHF with preserved left ventricular ejection fraction (HFpEF, n = 373), no benefit ensued from PDE5 inhibitor use regarding all of the investigated clinical, ergospirometric or hemodynamic endpoints.ConclusionsPDE5 inhibitors improved clinical outcomes, exercise capacity and pulmonary hemodynamics in patients with HFREF, but not in HFpEF. However, considering the relatively small size of the HFpEF subset enrolled so far in the RCTs that explored the PDE5 inhibitor effects, further research in this field is undoubtedly warranted.

Knowledge of the right atrial pressure (RAP) values is critical to ascertain the existence of a state of hemodynamic congestion, irrespective of the possible presence of signs and symptoms of clinical congestion and cardiac overload that can be lacking in some conditions of concealed or clinically misleading cardiac decompensation. In addition, a more reliable estimate of RAP would make it possible to determine more accurately also the systolic pulmonary arterial pressure with the only echocardiographic methods. The authors briefly illustrate some of the criteria that have been implemented to obtain a non-invasive RAP estimate, some of which have been approved by current guidelines and others are still awaiting official endorsement from the Scientific Societies of Cardiology. There is a representation of the sometimes opposing views of researchers who have studied the problem, and the prospects for development of new diagnostic criteria are outlined, in particular those derived from the matched use of two- and three-dimensional echocardiographic parameters.