Chronic Heart Research Articles

Cell-Based HIF1α Gene Therapy Reduces Myocardial Scar and Enhances Angiopoietic Proteome, Transcriptomic and miRNA Expression in Experimental Chronic Left Ventricular Dysfunction.

Recent preclinical investigations and clinical trials with stem cells mostly studied bone-marrow-derived mononuclear cells (BM-MNCs), which so far failed to meet clinically significant functional study endpoints. BM-MNCs containing small proportions of stem cells provide little regenerative potential, while mesenchymal stem cells (MSCs) promise effective therapy via paracrine impact. Genetic engineering for rationally enhancing paracrine effects of implanted stem cells is an attractive option for further development of therapeutic cardiac repair strategies. Non-viral, efficient transfection methods promise improved clinical translation, longevity and a high level of gene delivery. Hypoxia-induced factor 1α is responsible for pro-angiogenic, anti-apoptotic and anti-remodeling mechanisms. Here we aimed to apply a cellular gene therapy model in chronic ischemic heart failure in pigs. A non-viral circular minicircle DNA vector (MiCi) was used for in vitro transfection of porcine MSCs (pMSC) with HIF1α (pMSC-MiCi-HIF-1α). pMSCs-MiCi-HIF-1α were injected endomyocardially into the border zone of an anterior myocardial infarction one month post-reperfused-infarct. Cell injection was guided via 3D-guided NOGA electro-magnetic catheter delivery system. pMSC-MiCi-HIF-1α delivery improved cardiac output and reduced myocardial scar size. Abundances of pro-angiogenic proteins were analyzed 12, 24 h and 1 month after the delivery of the regenerative substances. In a protein array, the significantly increased angiogenesis proteins were Activin A, Angiopoietin, Artemin, Endothelin-1, MCP-1; and remodeling factors ADAMTS1, FGFs, TGFb1, MMPs, and Serpins. In a qPCR analysis, increased levels of angiopeptin, CXCL12, HIF-1α and miR-132 were found 24 h after cell-based gene delivery, compared to those in untreated animals with infarction and in control animals. Expression of angiopeptin increased already 12 h after treatment, and miR-1 expression was reduced at that time point. In total, pMSC overexpressing HIF-1α showed beneficial effects for treatment of ischemic injury, mediated by stimulation of angiogenesis.

MO001: Hydroelectrolytic Disorders During and Beyond the Month of Ramadan

Abstract BACKGROUND AND AIMS Fasting during Ramadan is religiously obligatory for Muslims, who account for 1.8 billion of the world's population (24%). The lifestyle habits of Muslims significantly change during Ramadan. The objective of this study is to determine the incidence of hospital admissions for electrolyte disturbances comparatively during Ramadan and the month before and to review the risk factors in a Tunisian population specimen. METHOD We carried out a retrospective study on the hospitalizations for hydroelectrolytic troubles in the nephrology department during Ramadan, i.e. April 2021 (group 1) and one a month earlier, i.e. March 2021 (group 2). RESULTS We have collected 14 patients for group 1 and 9 patients for group 2. The incidence of hospitalizations due to electrolytic disorders amounted to 46.6% for group 1 versus 20.9% for group 2. During Ramadan, the most frequently occurring ionic disorders were hyperkalemia in 71.4% (n = 10), hyponatremia in 21.4% of cases (n = 3) and hypernatremia in 7.1% of cases (n = 1). As compared with group 2, the ionic abnormalities encountered outside the month of youth were hyperkalemia in 66.6% of cases (n = 6), hyponatremia associated with hyperkalemia in 22.2% of cases (n = 2) and hypokalemia in 11.1% of cases (n = 1). All cases of hyponatremia were of depletion in group 1, hyperkalemia was due to dietary error with chronic renal failure, and hypernatremia was secondary to hydrosodic wasting. By reviewing the factors predisposing to develop hydrolytic disorders, we find a higher frequency in group 1 of hypertensive patients (78.5%), chronic kidney failure (35.7%), heart failure and diabetes (28% each) compared with group 2, six patients had hypertension (66.6%), three chronic kidney failure patients (33.3%), one diabetic patient (1.1%) and no patient had heart failure. CONCLUSION At the end of this study, we note that despite the occurrence of the month of Ramadan in spring and the tempered weather, the incidence of ion disorders remains high in a population at risk. Therefore, a strategy of nutritional and behavioral education during the Ramadan month is recommended, with the necessity of a close biological follow-up. This educational therapy must be individualized and specific for each individual patient, and adaptations of the medication are most required to avoid the development of ion disorders.

MO332: Acute Kidney Injury is Associated With Poor Long-Term Outcomes in Hospitalized Patients With COVID-19

BACKGROUND AND AIMSThe acute effects of the acute kidney injury (AKI) on short-term mortality in patients with novel coronavirus infection (COVID-19) have been studied, but the long-term outcomes after COVID-19-associated AKI are not well understood. Our aim was to evaluate the impact of AKI in acute COVID-19 in the prediction of long-term mortality in a population of hospitalized patients with COVID-19.METHODWe performed a cohort study on 1000 patients hospitalized from April to July 2020 with laboratory-confirmed COVID-19 and lung injury by computer tomography (CT). We excluded patients with re-hospitalization, acute surgical pathology and a single serum creatinine measurement during hospitalization. Definition of AKI was based on KDIGO criteria. According to the ESC guidelines, the term acute decompensated heart failure (ADHF) is used to describe patients with previously history of chronic stable heart failure with the typical symptoms and/or signs of decompensation of HF during hospitalization. Multivariate Cox regression was conducted to explore the potential predictors for long-term mortality. A P-value < 0.05 was considered statistically significant.RESULTSThe prospective part included 691/792 (87%) surviving patients [47% males, mean age 67 (55;78) years, mean Charlson index 3 (2;5), 69% with hypertension (HTN), 50% with obesity, 26% with diabetes mellitus (DM) and 15% with coronary artery disease (CAD)]. And 12.6% of patients were hospitalized in the intensive care unit (ICU).A total of 137 (20%) patients had AKI in acute COVID-19 and discharged from the hospital. The majority of survival patients with AKI had the 1 stage (77%), 17%—the 2 and 6%–the 3. There were no patients who underwent renal replacement therapy during acute COVID-19 in the survivors’ group. Patients with AKI were older [71 (62;78) versus 64 (52;73) years, P < .0001, compared with patients without AKI], had HTN (83% versus 66%, P < .001), DM (33% versus 24%, P = .03), CAD (25% versus 13%, P < .001) and higher Charlson index [4 (3;5) versus 3 (1;4), P < .0001]. Also, AKI patients had more severe lung injury by CT in acute COVID-19 (lung injuries >50%, 38% versus 26%, P = .004) and more frequently were hospitalized in ICU (23% versus 10%, P < .001). A total of 74% patients recovered from AKI at the discharge time.During 180 days of follow-up, 41 (6%) patients died in the whole study group. The most common cause of death was a heart attack or stroke (29%). In the group without AKI, the mortality rate was 4.5%, among patients with AKI—11.8% (P < .001). In multivariate Cox regression, AKI in the acute phase of COVID-19 [hazard ratio (HR) 2.83, 95% confidence interval (95% CI) 1.28–6.26; P = .01] and the Charlson index (HR 1.46, 95% CI 1.19–1.79; P < .001) were independently associated with higher mortality from all causes within 180 days after discharge after adjusting for age, gender, frequency of obesity, HTN, CAD, DM, ADHF, hospitalization in the ICU and lesions of more than 50% lung volume in the acute phase of COVID-19.CONCLUSIONAKI in the acute phase of COVID-19 and the Charlson index are independently associated with higher mortality within 180 days after discharge.Figure 1:A. Different urinary profiles in UPE. 1: Normal profile, 2: Tubular profile, 3: Glomerular profile, 3: Mixed profile. B. Urine protein assay in COVID ARDS patients with and without AKI KDIGO ≥ 2 in univariate analysis.

Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress: Overwintering in Antarctic Concordia Station.

Concordia Station is the permanent, research station on the Antarctic Plateau at 3230 m. During the eleventh winter-over campaign (DC11-2015; February 2015 to November 2015) at Antarctic Concordia Station, 13 healthy team members were studied and blood samples were collected at six different time points: baseline measurements (T0), performed at sea level before the departure, and during the campaign at 3, 7, 20, 90, and 300 days after arrival at Concordia Station. Reducing the partial pressure of O2 as barometric pressure falls, hypobaric hypoxia (HH) triggers several physiological adaptations. Among the others, increased oxidative stress and enhanced generation of reactive oxygen/nitrogen species (ROS/RNS), resulting in severe oxidative damage, were observed, which can share potential physiopathological mechanisms associated with many diseases. This study characterized the extent and time-course changes after acute and chronic HH exposure, elucidating possible fundamental mechanisms of adaptation. ROS, oxidative stress biomarkers, nitric oxide, and proinflammatory cytokines significantly increased (range 24-135%) during acute and chronic hypoxia exposure (peak 20th day) with a decrease in antioxidant capacity (peak 90th day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300th days, as all the observed variables do not return to the preexposition level. These findings may also be relevant to patients in whom oxygen availability is limited through disease (i.e., chronic heart and lung and/or kidney disease) and/or during long-duration space missions.

Risk factors and medical resource utilization in US adults hospitalized with influenza or respiratory syncytial virus in the Hospitalized Acute Respiratory Tract Infection study.

BackgroundInfluenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.MethodsHARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017–2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post‐discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, chronic heart or renal disease, chronic obstructive pulmonary disease, or asthma), and MRU were summarized descriptively.ResultsThe US cohort included 280 influenza‐positive and 120 RSV‐positive patients. RSV patients were older (mean: 63.1 vs. 59.7 years) and a higher proportion had CRFs (87.5% vs. 81.4%). Among those with CRFs (influenza, n = 153; RSV, n = 99), RSV patients required longer hospitalizations (median length of stay: 4.5 days) and a greater proportion (79.8%) required oxygen supplementation during hospitalization compared with influenza patients (4.0 days and 59.5%, respectively). At 3 months post‐discharge, a greater proportion of RSV patients with CRFs reported use of antibiotics, antitussives, bronchodilators, and inhaled and systemic steroids versus those with influenza and CRFs. Many patients with CRFs reported hospital readmission at 3 months post‐discharge (RSV: 13.4%; influenza: 11.9%).ConclusionsMRU during and post‐hospitalization due to RSV in adults is similar to or greater than that of influenza. Enhanced RSV surveillance and preventive and therapeutic interventions are needed.

Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption.

BackgroundTo compare clinical characteristics, outcomes, and resource consumption of patients with COVID-19 and seasonal influenza requiring supplemental oxygen.MethodsRetrospective cohort study conducted at a tertiary-care hospital. Patients admitted due to seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group.ResultsCOVID-19 cases were younger (median years, 67 (IQR 54-78) vs 76 (IQR 64-83); p < 0.001) and more frequently overweight whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory and renal disease. Compared to influenza, COVID-19 cases had more pneumonia (98% vs 60%, <0.001), higher MEWS and CURB-65 scores and were more likely to show worse progression on the WHO ordinal scale (33% vs 4%; p < 0.001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (p = 0.001). The median age of non-surviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (p = 0.385), respectively. COVID-19 was independently associated with 30-day (HR 4.6, 95%CI, 2-10.4) and 90-day (HR 5.2, 95%CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs.ConclusionsAlthough influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.

Сomorbidity of coronary artery disease and its significance in predicting the results of coronary artery bypass grafting

The review presents an analysis of the scientific literature on comorbidity of coronary artery disease (CAD) and assessment of its impact on the results of coronary artery bypass grafting (CABG). Arterial hypertension (AH), chronic obstructive pulmonary disease (COPD), metabolic syndrome (MS), and diabetes mellitus (DM) have been shown to be the most common comorbidities in CAD patients. Clinical manifestations of cardiovascular comorbidities also include atrial fibrillation, acute cerebral ischemia, atherosclerosis of carotid and lower limb arteries, and chronic heart failure.Concomitant COPD doubles the risk of postoperative complications after CABG and reduces the 10-year survival rate in patients to 30%. In CAD patients with MS, the risk of postoperative mortality increases by 1.4 times, and the 5-year survival rate decreases by 3 times. Diabetes significantly worsens the long-term survival of patients after CABG and is an independent predictor of acute cardiovascular events after revascularization in the long term. The presence of various comorbidities in CAD patients requires a personalized approach to managing the risks of adverse outcomes after CABG and introduction of modern artificial intelligence (AI) technologies into clinical practice, which significantly increase the accuracy of prognosis.

Chloroquine Decreased Kir6.2 Immunoreactivity in Chronic Hypoxic Heart

Chloroquine Decreased Kir6.2 Immunoreactivity in Chronic Hypoxic Heart

The importance of chronic conditions for potentially avoidable hospitalizations among non-Hispanic Black and non-Hispanic White older adults in the US: a cross-sectional observational study

BackgroundNon-Hispanic (NH) Black older adults experience substantially higher rates of potentially avoidable hospitalization compared to NH White older adults. This study explores the top three chronic conditions preceding hospitalization and potentially avoidable hospitalization among NH White and NH Black Medicare beneficiaries in the United States.MethodsData on 4993 individuals (4,420 NH White and 573 NH Black individuals) aged ≥ 65 years from 2014 Medicare claims were linked with sociodemographic data from previous rounds of the Health and Retirement Study. Conditional inference random forests were used to rank the importance of chronic conditions in predicting hospitalization and potentially avoidable hospitalization separately for NH White and NH Black beneficiaries. Multivariable logistic regression with the top three chronic diseases for each outcome adjusted for sociodemographic characteristics were conducted to quantify the associations.ResultsIn total, 22.1% of NH White and 24.9% of NH Black beneficiaries had at least one hospitalization during 2014. Among those with hospitalization, 21.3% of NH White and 29.6% of NH Black beneficiaries experienced at least one potentially avoidable hospitalization. For hospitalizations, chronic kidney disease, heart failure, and atrial fibrillation were the top three contributors among NH White beneficiaries and acute myocardial infarction, chronic obstructive pulmonary disease (COPD), and chronic kidney disease were the top three contributors among NH Black beneficiaries. These chronic conditions were associated with increased odds of hospitalization for both groups. For potentially avoidable hospitalizations, asthma, COPD, and heart failure were the top three contributors among NH White beneficiaries and fibromyalgia/chronic pain/fatigue, COPD, and asthma were the top three contributors among NH Black beneficiaries. COPD and heart failure were associated with increased odds of potentially avoidable hospitalization among NH White beneficiaries, whereas only COPD was associated with increased odds of potentially avoidable hospitalizations among NH Black beneficiaries.ConclusionHaving at least one hospitalization and at least one potentially avoidable hospitalization was more prevalent among NH Black than NH White Medicare beneficiaries. This suggests greater opportunity for increasing prevention efforts among NH Black beneficiaries. The importance of COPD for potentially avoidable hospitalizations further highlights the need to focus on prevention of exacerbations for patients with COPD, possibly through greater access to primary care and continuity of care.

Effect of advance care planning video on do-not-hospitalize orders for nursing home residents with advanced illness

BackgroundThe purpose of the study is to evaluate the effect of an Advance Care Planning (ACP) Video Program on documented Do-Not-Hospitalize (DNH) orders among nursing home (NH) residents with advanced illness.MethodsSecondary analysis on a subset of NHs enrolled in a cluster-randomized controlled trial (41 NHs in treatment arm implemented the ACP Video Program: 69 NHs in control arm employed usual ACP practices). Participants included long (> 100 days) and short (≤ 100 days) stay residents with advanced illness (advanced dementia or cardiopulmonary disease (chronic obstructive pulmonary disease or congestive heart failure)) in NHs from March 1, 2016 to May 31, 2018 without a documented Do-Not-Hospitalize (DNH) order at baseline. Logistic regression with covariate adjustments was used to estimate the impact of the resident being in a treatment versus control NH on: the proportion of residents with new DNH orders during follow-up; and the proportion of residents with any hospitalization during follow-up. Clustering at the facility-level was addressed using hierarchical models.ResultsThe cohort included 6,117 residents with advanced illness (mean age (SD) = 82.8 (8.4) years, 65% female). Among long-stay residents (n = 3,902), 9.3% (SE, 2.2; 95% CI 5.0–13.6) and 4.2% (SE, 1.1; 95% CI 2.1–6.3) acquired a new DNH order in the treatment and control arms, respectively (average marginal effect, (AME) 5.0; SE, 2.4; 95% CI, 0.3–9.8). Among short-stay residents with advanced illness (n = 2,215), 8.0% (SE, 1.6; 95% CI 4.6–11.3) and 3.5% (SE 1.0; 95% CI 1.5–5.5) acquired a new DNH order in the treatment and control arms, respectively (AME 4.4; SE, 2.0; 95% CI, 0.5–8.3). Proportion of residents with any hospitalizations did not differ between arms in either cohort.ConclusionsCompared to usual care, an ACP Video Program intervention increased documented DNH orders among NH residents with advanced disease but did not significantly reduce hospitalizations.Trial registration.ClinicalTrials.gov Identifier: NCT02612688.

Evaluation of Hospitalized Patients Receiving High versus Low-Dose Opioids for Non-Cancer Pain

Limited studies suggest that opioid-related adverse effects (ORAEs) may worsen hospitalized patient outcomes, but there is insufficient data related to the impact of high-dose opioids compared to low-dose on adverse patient events. Given the paucity of data, our study aims to evaluate these ORAEs in the general hospitalized patient with non-cancer pain. A retrospective study of adult patients receiving opioids with a primary diagnoses of myocardial infarction, chronic obstructive pulmonary disease, heart failure, pneumonia, sepsis, or diabetes was conducted. Average oral morphine milligram equivalents (MMEs) administered over the entire LOS was collected, and patients were categorized as high-dose (≥50 MMEs/day) or low-dose (<50 MMEs/day). The primary composite endpoint was the incidence of ORAEs (naloxone use, decreased oxygen saturations, nausea/vomiting). Secondary outcomes included LOS, 30-day readmission, ORAEs with >100 MMEs/day. A total of 100 patients were included (n = 58 low-dose group; n = 42 high-dose group). For the primary outcome, more patients in the high-dose group experienced ORAEs (50% high-dose vs. 22.4% low-dose; p < 0.006). No statistically significant differences in LOS or 30-day readmission rates were identified between the groups. For patients receiving >100 MMEs/day, ORAEs occurred in 61% of patients. Hospitalized patients receiving high-dose opioids for non-cancer pain may have an increased incidence of ORAEs.

Work stress and loss of years lived without chronic disease: an 18-year follow-up of 1.5 million employees in Denmark

We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30–59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02–1.05), men: HR 1.12 (95% CI 1.11–1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI − 0.10 to 0.60) and 0.84 (95% CI 0.56–1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.

Compliance to Advisory Committee on Immunization Practices recommendations for pneumococcal vaccination

We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan–Meier method.Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%).Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.

Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Short-Term Prognostic Factors in Hospitalized Herpes Zoster Patients and Its Associated Cerebro-Cardiovascular Events: A Nationwide Retrospective Cohort in Japan.

BackgroundShort-term mortality and incidence of cerebrovascular and cardiovascular events (C-CVE) during hospitalization of patients with severe herpes zoster (HZ) have not been sufficiently investigated. We aimed to investigate short-term prognosis and incidence of C-CVE associated with HZ in hospitalized patients.MethodsThis retrospective cohort study from April 2016 to March 2018 included HZ inpatient cases selected from the Diagnosis Procedure Combination database—a Japanese nationwide inpatient database. HZ and C-CVE were diagnosed based on the 10th revision of the International Classification of Diseases and Injuries codes. The definition of primary exposure was that treatments were initiated within 7 days of admission, and antivirals were administered for ≥7 days. Main Outcomes were in-hospital deaths and C-CVE onset after hospitalization.ResultsAmong 16,811,501 in-hospital cases registered from 1,208 hospitals, 29,054 cases with HZ were enrolled. The median age was 71.0 years, 15,202 cases (52.3%) were female, and the HZ types were the central nervous system (n=9,034), disseminated (n=3,051), and ophthalmicus (n=1,069) types. There were 301 (1.0%) in-hospital deaths and 385 (1.3%) post-hospitalization onset of C-CVE. The 30-day in-hospital survival rates with or without underlying disease were 96.8% and 98.5%, respectively. Age ≥75 years (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.55–3.05), liver cirrhosis or hepatic failure (HR, 5.93; 95% CI, 2.16–16.27), chronic kidney disease (HR, 1.82; 95% CI, 1.24–2.68), heart failure (HR, 1.65; 95% CI, 1.22–2.24), and old cerebrovascular events (HR, 1.92; 95% CI, 1.10–3.34) were associated with poor short-term prognosis. Age ≥75 years (odds ratio [OR], 1.70; 95% CI, 1.29–2.24), diabetes (OR, 1.50; 95% CI, 1.19–1.89), dyslipidemia (OR, 1.95; 95% CI, 1.51–2.51), hyperuricemia (OR, 1.63; 95% CI, 1.18–2.27), hypertension (OR, 1.76; 95% CI, 1.40–2.20), heart failure (OR, 1.84; 95% CI, 1.32–2.55), and glucocorticoid administration (OR, 1.59; 95% CI, 1.25–2.01) were associated with increased risks for in-hospital C-CVE onset.ConclusionsThe underlying diseases that could influence the short-term mortality of severe HZ were identified. Glucocorticoid is a possible risk factor for the in-hospital onset of C-CVE after severe HZ development.

Characteristics of Obese Patients with Acute Hypercapnia Respiratory Failure Admitted in the Department of Pneumology: An Observational Study of a North African Population.

Background Acute hypercapnic respiratory failure (AHRF) is a common life-threatening event in patients with obesity hypoventilation syndrome (OHS). Objectives To study the clinical pattern, noninvasive ventilatory support, as well as the short- and long-term outcomes of patients with OHS admitted in a ward because of AHRF. Methods We conducted a retrospective cohort study including all adults with OHS aged ≥ 18 − year − old, admitted in a 90-bed-ward for AHRF. Results A total of 44 patients were included. Fifteen (34.1%) and 29 (65.9%) patients were diagnosed with malignant OHS (mOHS) and nonmalignant OHS (non-mOHS), respectively, while 36 (81.8%) had coexisting obstructive sleep apnea hypopnea syndrome (OSAHS). Patients with mOHS had a significantly higher rate of heart failure (100% vs. 31%; p < 0.001), chronic renal insufficiency (CRI) (73.3% vs. 41.4%; p = 0.04), and dyslipidemia (66.7% vs. 34.5%; p = 0.04) than those with non-mOHS. The mean forced vital capacity (FVC) in our patients was of 59.5% ± 18.5 of the predicted value, lower than what is usually reported in stable patients with OHS. At hospital admission, more than two-thirds (n = 34, 77.3%) were misdiagnosed as having asthma exacerbation (n = 4, 4.9.1%), chronic obstructive pulmonary disease (COPD) exacerbation (n = 12, 27.3%) and/or heart failure (n = 29, 65.9%). Acute pulmonary oedema (ACPE) (n = 16, 36.4%) and acute viral bronchitis (n = 12, 27.3%) were the main identified causal factors, while no cause could be determined in 5 (11.4%) patients. Noninvasive positive pressure ventilation (NIPPV) using bilevel positive airway pressure (BIPAP) was very highly effective to treat AHRF, with only 2.27% of patients failing the modality. Median overall duration of ventilation was 9 hours per day (1.3–20) and was significantly longer in patients with mOHS than in those with non-mOHS (10 [6–18] vs. 8 [1.3–20], respectively; p = 0.01). Forty two of the forty-three patients discharged alive were treated with BIPAP or continuous positive airway pressure (CPAP) in 26 and 16 patients, respectively. The probability of survival was 90% at 12 months, while the probability of readmission for a new episode of AHRF was 56% at 6 months and 22% at 12 months, respectively. Conclusion AHRF in OHS patients is a life-threatening event which can be successfully and safely treated with BIPAP, with a low long-term mortality even in patients with mOHS.

Chronic, Combined Cardiac and Renal Dysfunction Exacerbates Renal Venous Pressure-Induced Suppression of Renal Function in Rats.

Background and ObjectiveIncreased renal venous pressure (RVP) is common in combined heart and kidney failure. We previously showed that acute RVP elevation depresses renal blood flow (RBF), glomerular filtration rate (GFR), and induces renal vasoconstriction in the absence of changes in blood pressure in healthy rats. We used our established rodent model of chronic combined heart and kidney failure (H/KF) to test whether RVP elevation would impair cardiovascular stability, renal perfusion and exacerbate renal dysfunction.MethodsMale rats were subjected to 5/6 nephrectomy (SNx or Sham) and 6% high salt diet followed 7 weeks later by ligation of the left anterior descending coronary artery (CL or Sham). Experimental groups: CL + SNx (n = 12), Sham CL + SNx (n = 9), CL+ Sham SNx (n = 6), and Sham Control (n = 6). Six weeks later, anesthetized rats were subjected to an acute experiment whereupon mean arterial pressure (MAP), heart rate (HR), RVP, RBF, and GFR were measured at baseline and during elevation of RVP to 20–25 mmHg for 120 min.ResultsBaseline MAP, HR, RBF, and renal vascular conductance (RVC) were comparable among groups. Baseline GFR was significantly depressed in CL + SNx and Sham CL + SNx groups compared to Sham Control and CL + Sham SNx groups. Upon RVP increase, MAP and HR fell in all groups. Increased RVP exacerbated the reduction in RBF in CL + SNx (−6.4 ± 0.9 ml/min) compared to Sham Control (−3.7 ± 0.9 ml/min, p < 0.05) with intermediate responses in Sham CL + SNx (−6.8 ± 1.3 ml/min) and CL + Sham SNx (−5.1 ± 0.4 ml/min) groups. RVP increase virtually eliminated GFR in CL + SNx (−99 ± 1%), Sham CL + SNx (−95 ± 5%), and CL + Sham SNx (−100%) groups compared to Sham Control (−84 ± 15% from baseline; p < 0.05). Renal vascular conductance dropped significantly upon RVP increase in rats with HF (CL + SNx: −0.035 ± 0.011; CL + Sham SNx: −0.050 ± 0.005 ml/min·mmHg−1, p < 0.05) but not Sham CL + SNx (−0.001 ± 0.019 ml/min·mmHg−1) or Control (−0.033 ± mL/min·mmHg−1).ConclusionChronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats.

Can Non-invasive Ventilation Modulate Cerebral, Respiratory, and Peripheral Muscle Oxygenation During High-Intensity Exercise in Patients With COPD-HF?

AimTo evaluate the effect of non-invasive positive pressure ventilation (NIPPV) on (1) metabolic, ventilatory, and hemodynamic responses; and (2) cerebral (Cox), respiratory, and peripheral oxygenation when compared with SHAM ventilation during the high-intensity exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and heart failure (HF).Methods and ResultsOn separate days, patients performed incremental cardiopulmonary exercise testing and two constant-work rate tests receiving NIPPV or controlled ventilation (SHAM) (the bilevel mode—Astral 150) in random order until the limit of tolerance (Tlim). During exercise, oxyhemoglobin (OxyHb+Mb) and deoxyhemoglobin (DeoxyHb+Mb) were assessed using near-infrared spectroscopy (Oxymon, Artinis Medical Systems, Einsteinweg, The Netherlands). NIPPV associated with high-intensity exercise caused a significant increase in exercise tolerance, peak oxygen consumption ( in mlO2·kg−1·min−1), minute ventilation peak ( in ml/min), peak peripheral oxygen saturation (SpO2, %), and lactate/tlim (mmol/s) when compared with SHAM ventilation. In cerebral, respiratory, and peripheral muscles, NIPPV resulted in a lower drop in OxyHb+Mb (p < 0.05) and an improved deoxygenation response DeoxyHb+Mb (p < 0.05) from the half of the test (60% of Tlim) when compared with SHAM ventilation.ConclusionNon-invasive positive pressure ventilation during constant work-rate exercise led to providing the respiratory muscle unloading with greater oxygen supply to the peripheral muscles, reducing muscle fatigue, and sustaining longer exercise time in patients with COPD-HF.

Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages

BackgroundThe leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease.MethodsWe assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2−/− and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors.ResultsWe found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts.ConclusionsThis study provides new insight into the role of the innate immune system in uremic cardiomyopathy.

Оценка и прогнозирование респираторных нарушений при заболеваниях легких, связанных с воздействием фиброгенных аэрозолей

Актуальность. У лиц, работающих в условиях воздействия промышленных аэрозолей фиброгенной и/или химической природы частой проблемой является поздняя постановка диагноза профессионального заболевания бронхолегочной системы. В настоящее время наиболее достоверной и общепринятой методикой исследования функции внешнего дыхания является регистрация и анализ кривых «поток — объем», осуществляемых при помощи микропроцессорной техники. Цель исследования: оценка и прогнозирование респираторных нарушений при заболеваниях легких, связанных с воздействием фиброгенных аэрозолей.Материалы и методы.Проведено комплексное исследование функции внешнего дыхания у 153 человек с различными профессиональными заболеваниями легких в сравнении с данными 60 здоровых людей. Больным проведено бронхоскопическое исследование и компьютерная пневмотахография.Вывод. С целью ранней диагностики гиперреактивности бронхов у лиц, контактирующих на производстве с промышленными фиброгенными аэрозолями, и уточнения степени функциональных нарушений при хроническом пылевом бронхите, силикозе, пневмокониозе от воздействия сварочных аэрозолей необходимо проводить определение таких показателей форсированного выдоха, как FVC, FEV1, FEV1/FVC, PEF, MEF25 %VC, MEF50 %VC, MEF75 %VC и Rfo, изменение которых может служить первичным функциональным физиологическим маркером предболезни при профессиональных заболеваниях легких. Компьютерная пневмотахография позволяет достоверно выявлять ранние формы пылевых заболеваний легких, дифференцировать их различные клинико-функциональные типы, что повышает качество ранней диагностики, вторичной профилактики, терапии и реабилитации при данной патологии, позволяет избежать развития и прогрессирования осложнений пылевых заболеваний легких, и прежде всего хронического легочного сердца.