Risk stratification is central to the management of pulmonary arterial hypertension (PAH). For this purpose, multiparametric tools have been developed, including the ESC/ERS risk score and its ...simplified versions derived from large database analysis such as the COMPERA and the French Pulmonary Hypertension Network (FPHN) registries. However, the distinction between high and intermediate-risk profiles may be difficult as the latter lacks granularity. In addition, neither COMPERA or FPHN strategies included imaging-derived markers. We thus aimed at investigating whether surrogate echocardiographic markers of right ventricular (RV) to pulmonary artery (PA) coupling could improve risk stratification in patients at intermediate-risk.
A single-center retrospective analysis including 102 patients with a diagnosis of PAH was performed. COMPERA and FPHN strategies were applied to stratify clinical risk. The univariate linear regression was used to test the influence of the echo-derived parameters qualifying the right heart (right ventricle basal diameter, right atrial area, and pressure, tricuspid regurgitation velocity, tricuspid annular plane systolic excursion -TAPSE-). Among these, the TAPSE and tricuspid regurgitation velocity ratio (TAPSE/TRV) as well as the TAPSE and systolic pulmonary artery pressure ratio (TAPSE/sPAP) were considered as surrogate of RV-PA coupling.
TAPSE/TRV and TAPSE/sPAP resulted the more powerful markers of prognosis. Once added to COMPERA, TAPSE/TRV or TAPSE/sPAP significantly dichotomized intermediate-risk group in intermediate-to-low-risk (TAPSE/TRV≥3.74 mm∙nm/s)-1 or TAPSE/sPAP≥0.24 mm/mmHg) and in intermediate-to-high-risk subgroups (TAPSE/TRV<3.74 mm∙(m/s)-1 or TAPSE/sPAP<0.24 mm/mmHg). In the same way, TAPSE/TRV or TAPSE/sPAP was able to select patients at lower risk among those with 2, 1, and 0 low-risk criteria of both invasive and non-invasive FPHN registries.
Our results suggest that adopting functional-hemodynamic echo-derived parameters may provide a more accurate risk stratification in patients with PAH. In particular, TAPSE/TRV or TAPSE/sPAP improved risk stratification in patients at intermediate-risk, that otherwise would have remained less characterized.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SARS-CoV-2 symptoms are non-specific and can range from asymptomatic presentation to severe pneumonia. Asymptomatic subjects carrying SARS-CoV-2 often remain undiagnosed and it is still debated ...whether they develop immunoglobulins (Ig) and how long they persist. The aim of this study was to investigate the development and persistence of antibodies against SARS-CoV-2 in asymptomatic subjects infected by the virus. This follow-up study was performed on the 31 asymptomatic subjects who presented a positive nasal swab or serology against SARS-CoV-2 (Ig against Spike-RBD) in the first part of the UNICORN study (March 2020) aimed at attesting previous or current contacts with the virus in the personnel of the University of Milan. Eight weeks after the first Ig measure, these subjects were invited to donate a second blood sample for testing serum antibodies (IgM, IgG and total antibodies) and to fill-in a structured questionnaire. About 80% of asymptomatic subjects did not present circulating immunoglobulins against SARS-CoV-2 after 8 weeks from a positive nasal swab against the virus. Moreover, in more than 40% of these subjects, no Ig against SARS-CoV-2 were detected at any time. Finally, about two third of subjects with immunoglobulins at baseline did not present IgG against SARS-CoV-2 after 8 weeks. The majority of subjects who developed an asymptomatic SARS-CoV-2 infection do not present antibodies against the RBD-spike protein after 8 weeks of follow-up. These data should be taken into account for the interpretation of the serological evidences on SARS-CoV-2 that are emerging nowadays.
Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure Marco Guazzi, Michele Samaja, Ross Arena, Marco Vicenzi, Maurizio D. Guazzi We tested whether chronic phosphodiesterase 5 ...inhibition by sildenafil is beneficial in heart failure. A total of 46 heart failure patients were randomly assigned to placebo (23 patients) or sildenafil (23 patients), with 3- and 6-month assessments of cardiopulmonary exercise test performance, brachial artery flow-mediated maximal dilatation, and ergoreflex responses. Sildenafil and not placebo improved flow-mediated maximal dilatation, ergoreflex effect on ventilation, exercise ventilation to CO2 production slope, and breathlessness, at both 3 and 6 months (p < 0.01). Findings suggest that benefits of sildenafil in heart failure are sustained and that an endothelium-mediated modulation of the muscle ergoreflex oversignaling may be at work.
•Short-term PM10 and PM2.5 exposures were associated with increased concentrations of plasmatic EVs.•Increased Sync-1 + EV levels were associated with the plasmatic decrease of the circulating ...endothelial dysfunction biomarker sVCAM-1.•The EV-miRNA dysregulated in response to both PM10 and PM2.5 exposures exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia.
The impact of exposure to respirable particulate matter (PM) during pregnancy is a growing concern, as several studies have associated increased risks of adverse pregnancy and birth outcomes, and impaired intrauterine growth with air pollution. The molecular mechanisms responsible for such effects are still under debate. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues (e.g., pulmonary environment and placenta), might play an important role in PM-induced risk. We sought to determine whether the levels of PM with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) are associated with changes in plasmatic EV release and EV-miRNA content by investigating 518 women enrolled in the INSIDE study during the first trimester of pregnancy. In all models, we included both the 90-day averages of PM (long-term effects) and the differences between the daily estimate of PM and the 90-day average (short-term effects). Short-term PM10 and PM2.5 were associated with increased concentrations of all seven EV types that we assayed (positive for human antigen leukocyte G (HLA-G), Syncytin-1 (Sync-1), CD14, CD105, CD62e, CD61, or CD25 determinants), while long-term PM10 showed a trend towards decreased EV concentrations. Increased Sync-1 + EV levels were associated with the plasmatic decrease of sVCAM-1, but not of sICAM-1, which are circulating biomarkers of endothelial dysfunction. Thirteen EV-miRNAs were downregulated in response to long-term PM10 and PM2.5 variations, while seven were upregulated (p-value < 0.05, false discovery rate p-value (qFDR) < 0.1). Only one EV-miRNA (hsa-miR-221-3p) was downregulated after short-term variations. The identified PM-modulated EV-miRNAs exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia, as highlighted by miRNA target analysis. Our findings strongly support the hypothesis that EVs have an important role in modulating PM exposure effects during pregnancy, possibly through their miRNA cargo.
Cardiac involvement has been frequently reported in COVID-19 as responsible of increased morbidity and mortality. Given the importance of right heart function in acute and chronic respiratory ...diseases, its assessment in SARS-CoV-2 infected patients may add prognostic accuracy. Transthoracic echocardiography has been proposed to early predict myocardial injury and risk of death in hospitalized patients. This systematic review presents the up-to-date sum of literature regarding right ventricle ultrasound assessment. We evaluated commonly used echocardiographic parameters to assess RV function and discussed their relationship with pathophysiological mechanisms involved in COVID-19. We searched Medline and Embase for studies that used transthoracic echocardiography for right ventricle assessment in patients with COVID-19.
COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic ...inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is advisable for segregation purpose as well as for infection control. In this article we present the standard operating procedures of our COVID-19 high dependency unit of the Policlinico Hospital, in Milan. Our high dependency unit is based on a multidisciplinary approach. We think that the multidisciplinary involvement of several figures can better identify treatable traits of COVID-19 disease, early identify patients who can quickly deteriorate, particularly patients with multiple comorbidities, and better manage complications related to off-label treatments. Although no generalizable to other hospitals and different healthcare settings, we think that our experience and our point of view can be helpful for countries and hospitals that are now starting to face the COVID-19 outbreak.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Despite the emerging clinical relevance of heart rate variability (HRV) as a potential biomarker of cognitive decline and as a candidate target for intervention, there is a dearth of ...research on the prospective relationship between HRV and cognitive change. In particular, no study has addressed this issue in subjects with a diagnosis of cognitive status including cognitive impairment.
Objective
To investigate HRV as a predictor of cognitive decline in subjects with normal cognition (NC) or Mild Cognitive Impairment (MCI). Specifically, we tested the literature-based hypothesis that the HRV response to different physical challenges would predict decline in different cognitive domains.
Methods
This longitudinal study represents the approximately 3-year follow-up of a previous cross-sectional study enrolling 80 older outpatients (aged ≥ 65). At baseline, power spectral analysis of HRV was performed on five-minute electrocardiographic recordings at rest and during a sympathetic (active standing) and a parasympathetic (paced breathing) challenge. We focused on normalized HRV measures normalized low frequency power (LFn) and the low frequency to high frequency power ratio (LF/HF) and on their dynamic response from rest to challenge (Δ HRV). Extensive neuropsychological testing was used to diagnose cognitive status at baseline and to evaluate cognitive change over the follow-up
via
annualized changes in cognitive Z-scores. The association between Δ HRV and cognitive change was explored by means of linear regression, unadjusted and adjusted for potential confounders.
Results
In subjects diagnosed with MCI at baseline a greater response to a sympathetic challenge predicted a greater decline in episodic memory adjusted model: Δ LFn, standardized regression coefficient (β) = −0.528,
p
= 0.019; Δ LF/HF, β = −0.643,
p
= 0.001 whereas a greater response to a parasympathetic challenge predicted a lesser decline in executive functioning (adjusted model: Δ LFn, β = −0.716,
p
< 0.001; Δ LF/HF, β = −0.935,
p
< 0.001).
Conclusion
Our findings provide novel insight into the link between HRV and cognition in MCI. They contribute to a better understanding of the heart-brain connection, but will require replication in larger cohorts.
Exercise Oscillatory Ventilation May Predict Sudden Cardiac Death in Heart Failure Patients Marco Guazzi, Rosa Raimondo, Marco Vicenzi, Ross Arena, Chiara Proserpio, Simona Sarzi Braga, Roberto ...Pedretti In 156 chronic heart failure (CHF) patients, we tested the ability of cardiopulmonary exercise testing-derived variables as predictors of sudden cardiac death (SCD). Over a mean tracking period of 27.8 ± 25.2 months, 17 patients died from SCD and 17 from pump failure. Peak oxygen uptake and ventilatory requirement/carbon dioxide production slope were not different between sudden and pump failure death groups, whereas exercise oscillatory breathing (EOB) was significantly more prevalent in the SCD group (p < 0.001). Multivariate analysis selected EOB as the strongest predictor of both overall mortality (chi-square: 38.7, p < 0.001) and SCD (chi-square: 44.7, p < 0.001). Exercise oscillatory breathing is possibly an independent predictor of SCD in CHF patients.