Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review.

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.

COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?

Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling leading to right heart failure and death. To date, despite the three therapeutic approaches targeting the three major endothelial dysfunction pathways based on the prostacyclin, nitric oxide/cyclic guanosine monophosphate, and endothelin pathways, PAH remains a serious disease. As such, new targets and therapeutic agents are needed. Mitochondrial metabolic dysfunction is one of the mechanisms involved in PAH pathogenesis in part through the induction of a Warburg metabolic state of enhanced glycolysis but also through the upregulation of glutaminolysis, tricarboxylic cycle and electron transport chain dysfunction, dysregulation of fatty acid oxidation or mitochondrial dynamics alterations. The aim of this review is to shed light on the main mitochondrial metabolic pathways involved in PAH and to provide an update on the resulting interesting potential therapeutic perspectives.

An emerging phenotype of pulmonary arterial hypertension patients carrying SOX17 variants.

BACKGROUND: The phenotype of pulmonary arterial hypertension (PAH) patients carrying SOX17 pathogenic variants remains mostly unknown. METHODS: We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying SOX17 variants from the French Pulmonary Hypertension Network. RESULTS: 20 patients and eight unaffected relatives were identified. The median (range) age at diagnosis was 17 (2-53) years, with a female:male ratio of 1.5. At diagnosis, most of the patients (74%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise, including a median pulmonary vascular resistance of 14.0 (4.2-31.5) WU. An associated congenital heart disease (CHD) was found in seven PAH patients (35%). Patients with CHD-associated PAH were significantly younger at diagnosis than PAH patients without CHD. Four patients (20%) suffered from recurrent haemoptysis requiring repeated arterial embolisations. 13 out of 16 patients (81%) for whom imaging was available displayed chest computed tomography abnormalities, including dilated, tortuous pulmonary vessels, ground-glass opacities as well as anomalies of the bronchial and nonbronchial arteries. After a median (range) follow-up of 47 (1-591) months, 10 patients underwent lung transplantation and one patient benefited from a heart-lung transplantation due to associated CHD. Histopathological analysis of lung explants showed a congested lung architecture with severe pulmonary arterial remodelling, subpleural vessel dilation and numerous haemorrhagic foci. CONCLUSIONS: PAH due to SOX17 pathogenic variants is a severe phenotype, frequently associated with CHD, haemoptysis and radiological abnormalities. Pathological assessment reveals severe pulmonary arterial remodelling and malformations affecting pulmonary vessels and thoracic systemic arteries.

Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension.

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Pulmonary Hypertension in Patients with Common Variable Immunodeficiency.

PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.

Acute adrenal infarction as an incidental CT finding and a potential prognosis factor in severe SARS-CoV-2 infection: a retrospective cohort analysis on 219 patients.

OBJECTIVES: To retrospectively investigate the incidence of acute adrenal infarction (AAI) in patients who underwent chest CT for severe SARS-CoV-2 infection and to correlate findings with prognosis. METHODS: The local ethics committee approved this retrospective study and waived the need of informed consent. From March 9 to April 10, 2020, all patients referred to our institution for a clinical suspicion of COVID-19 with moderate to severe symptoms underwent a chest CT for triage. Patients with a/parenchymal lesion characteristics of COVID-19 involving at least 50% of lung parenchyma and b/positive RT-PCR for SARS-CoV-2 were retrospectively included. Adrenal glands were reviewed by two independent readers to look for AAI. Additional demographics and potential biological markers of adrenal insufficiency were obtained. Correlations with ICU stay and mortality were sought. RESULTS: Out of the 219 patients with critical (n = 52) and severe lung (n = 167) parenchyma lesions, 51 (23%) had CT scan signs of AAI, which was bilateral in 45 patients (88%). Four patients had an acute biological adrenal gland insufficiency (8%). Univariate analysis in AAI+ patients demonstrated a higher rate of ICU stay (67% vs. 45%, p < 0.05) and a longer stay (more than 15 days for 31% for AAI+ vs. 19%, p < 0.05) compared with AAI- patients. Mortality rate was similar (27%, p = 0.92). CONCLUSIONS: Acute adrenal infarction on initial chest evaluation of severe COVID-19 is frequent (51/219, 23%) and might be a sign of poorer prognosis. KEY POINTS: • Acute adrenal infarction on initial chest CT evaluation of severe COVID-19 is frequent (51/219). • AAI might be a factor of poorer prognosis, with increased rate of ICU hospitalization and length of stay.

Usefulness of Platelet-to-Lymphocyte Ratio as a Marker of Sarcopenia for Critical Limb Threatening Ischemia.

BACKGROUND: Sarcopenia is a factor of poor prognosis for patients with critical limb threatening ischemia (CLTI), but its diagnosis requires imaging measurements and is time consuming. We investigated whether preoperative platelet-to-lymphocyte ratio (PLR) could be an easy and rapid marker of sarcopenia. METHODS: Patients treated for CLTI between January 2019 and July 2019 were included in this single-center retrospective study. Sarcopenia was defined by a psoas muscle index (PMI) <5.5 cm2/m2 in men, and <4.0 cm2/m2 in women. PLR was calculated for all patients based on their systematic preoperative blood analysis. The diagnostic power of PLR was analyzed through a receiver operating characteristic (ROC) curve. Early outcomes of sarcopenic patients in terms of 30-day mortality and 30-day morbidity were retrieved. RESULTS: Sixty-four patients were included in the study: 48 nonsarcopenic patients (mean PMI 7.34 cm2/m2; interquartile range [IQR] 6.58-8.01) and 16 sarcopenic patients (mean PMI 4.30 cm2/m2; IQR 3.45-5.17). No difference was found between both groups regarding patient demographics, clinical characteristics, cardiovascular risk factors, comorbidities, or revascularization modalities. PLR was significantly higher in the sarcopenic group (mean 332.1; IQR 158.2-320.7) compared with the nonsarcopenic group (mean 204.6; IQR 133.8-265.6) (P = 0.02). A PLR value ≥292.5 was shown to be a diagnostic marker for sarcopenia based on the ROC curve (sensitivity 31.3%, specificity 91.7%). Thirty-day mortality was 12.5% in the sarcopenic group and 2.1% in the nonsarcopenic group (P = 0.15); 30-day morbidity was 56.3% in the sarcopenic group and 10.4% in the nonsarcopenic group (P < 0.001). CONCLUSIONS: PLR might help identifying a subgroup of CTLI patients associated with poor prognosis but does not seem appropriate to be used as a marker of sarcopenia given its low sensitivity.

Bmpr2 Mutant Rats Develop Pulmonary and Cardiac Characteristics of Pulmonary Arterial Hypertension.

BACKGROUND: Monoallelic mutations in the gene encoding bone morphogenetic protein receptor 2 ( Bmpr2) are the main genetic risk factor for heritable pulmonary arterial hypertension (PAH) with incomplete penetrance. Several Bmpr2 transgenic mice have been reported to develop mild spontaneous PAH. In this study, we examined whether rats with the Bmpr2 mutation were susceptible to developing more severe PAH. METHODS: The zinc finger nuclease method was used to establish rat lines with mutations in the Bmpr2 gene. These rats were then characterized at the hemodynamic, histological, electrophysiological, and molecular levels. RESULTS: Rats with a monoallelic deletion of 71 bp in exon 1 (Δ 71 rats) showed decreased BMPRII expression and phosphorylated SMAD1/5/9 levels. Δ 71 Rats develop age-dependent spontaneous PAH with a low penetrance (16%-27%), similar to that in humans. Δ 71 Rats were more susceptible to hypoxia-induced pulmonary hypertension than wild-type rats. Δ 71 Rats exhibited progressive pulmonary vascular remodeling associated with a proproliferative phenotype and showed lower pulmonary microvascular density than wild-type rats. Organ bath studies revealed severe alteration of pulmonary artery contraction and relaxation associated with potassium channel subfamily K member 3 (KCNK3) dysfunction. High levels of perivascular fibrillar collagen and pulmonary interleukin-6 overexpression discriminated rats that developed spontaneous PAH and rats that did not develop spontaneous PAH. Finally, detailed assessments of cardiomyocytes demonstrated alterations in morphology, calcium (Ca2+), and cell contractility specific to the right ventricle; these changes could explain the lower cardiac output of Δ 71 rats. Indeed, adult right ventricular cardiomyocytes from Δ 71 rats exhibited a smaller diameter, decreased sensitivity of sarcomeres to Ca2+, decreased [Ca2+] transient amplitude, reduced sarcoplasmic reticulum Ca2+ content, and short action potential duration compared with right ventricular cardiomyocytes from wild-type rats. CONCLUSIONS: We characterized the first Bmpr2 mutant rats and showed some of the critical cellular and molecular dysfunctions described in human PAH. We also identified the heart as an unexpected but potential target organ of Bmpr2 mutations. Thus, this new genetic rat model represents a promising tool to study the pathogenesis of PAH.

Portopulmonary hypertension in the current era of pulmonary hypertension management.

BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Familial pulmonary arterial hypertension by KDR heterozygous loss of function.

Beyond the major gene BMPR2, several new genes predisposing to PAH have been identified during the last decade. Recently, preliminary evidence of the involvement of the KDR gene was found in a large genetic association study.We prospectively analysed the KDR gene by targeted panel sequencing in a series of 311 PAH patients referred to a clinical molecular laboratory for genetic diagnosis of PAH.Two index cases with severe PAH from two different families were found to carry a loss-of-function mutation in the KDR gene. These two index cases were clinically characterised by low diffusing capacity for carbon monoxide adjusted for haemoglobin (D LCOc) and interstitial lung disease. In one family, segregation analysis revealed that variant carriers are either presenting with PAH associated with low D LCOc, or have only decreased D LCOc, whereas non-carrier relatives have normal D LCOc. In the second family, a single affected carrier was alive. His carrier mother was unaffected with normal D LCOc.We provided genetic evidence for considering KDR as a newly identified PAH-causing gene by describing the segregation of KDR mutations with PAH in two families. In our study, KDR mutations are associated with a particular form of PAH characterised by low D LCOc and radiological evidence of parenchymal lung disease including interstitial lung disease and emphysema.

The social and clinical impact of the COVID-19 epidemic on the Strasbourg lung transplant cohort: A single-center retrospective cohort study.

The clinical and social impacts of the COVID-19 epidemic on lung transplant (LTx) recipients remain poorly known. We aimed to evaluate its social, clinical, and behavioral consequences on the LTx patients followed in Strasbourg university hospital. A questionnaire was used to collect details concerning patients' lifestyles, their protection methods used to avoid COVID-19 contamination, and clinical infection-related information for March 2020. A specific score was created to quantify patients' contacts and the associated risk of infectious contagion. Data were collected from 322 patients (91.2%). A majority reported a higher application than usual of social distancing and barrier measures. 43.8% described infectious-related symptoms and 15.8% needed an anti-infective treatment. There was no difference in symptom onset according to age, native lung disease, diabetes, or obesity. Nineteen patients were tested for COVID-19, and four were diagnosed positive, all with a favorable outcome. The infection risk contact score was higher for symptomatic patients (p: 0.007), those needing extra-medical appointments (p < .001), and those receiving anti-infective treatments (p = .02). LTx patients reported a careful lifestyle and did not seem at higher risk for COVID-19. Our score showed encouraging preliminary results and could become a useful tool for the usual infection-related follow-up of the LTx patients.

Impact of the COVID-19 pandemic on lung transplant patients and on a cohort of patients with rare lung disease: A single-center study.

INTRODUCTION: Due to the COVID-19 pandemic, France underwent several lockdown periods during 2020. Our aim was to evaluate its clinical and social impact on lung transplant (LT) patients treated at Strasbourg University Hospital, by comparing three periods: first lockdown (T1: March-May 2020), end of the first lockdown (T2: May-October 2020), and second lockdown (T3: November-December 2020) and the incidence of COVID-19 infections. A cohort of patients with rare lung disease (RLD) was also studied during T2. METHODS: We used clinical and paraclinical data collected during routine follow-up. A questionnaire was submitted to each patient at each period to assess their lifestyle, adherence to protective measures against COVID-19, contacts with their family and friends, and contagion risk. The incidence of new COVID-19 cases was also assessed. RESULTS: Overall, 283 LT and 57 RLD patients were included. We observed only eight COVID-19 cases over the three periods (n = 4 during T1, n = 0 during T2, and n = 4 during T3) in LT patients, with 37.5 % of patients hospitalized, no ICU transfers, and 100 % favorable outcomes. No case of COVID-19 was diagnosed in the RLD cohort. When comparing the three periods in the LT group, fewer patients limited their out-of-home activities during T2 (p < 0.0001). The frequency of these activities increased after the first lockdown, for the purchase of basic necessities (p < 0.0001), and professional activity continued (p = 0.008). We observed a significant increase in unscheduled medical consultations and in the prescription of anti-infective treatments during the end of the lockdown (p = 0.0002 and p = 0.005, respectively). Adherence to lockdown and to protective measures was high in both groups of patients. CONCLUSION: COVID-19 incidence remained low in both groups and there were significant lifestyle evolutions in LT patients and in those with RLD between first and second lockdown.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype.

BACKGROUND: The aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. MATERIAL AND METHODS: We retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. RESULTS: From 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (-39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16-7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08-17.42]; p = 0.04). CONCLUSIONS: Our study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

Evidence and unresolved questions in pulmonary hypertension: Insights from the 5th French Pulmonary Hypertension Network Meeting.

Pulmonary hypertension (PH) continues to present significant challenges to the medical community, both in terms of diagnosis and treatment. The advent of the updated 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines has introduced pivotal changes that reflect the rapidly advancing understanding of this complex disease. These changes include a revised definition of PH, updates to the classification system, and treatment algorithm. While these guidelines offer a critical framework for the management of PH, they have also sparked new discussions and questions. The 5th French Pulmonary Hypertension Network Meeting (Le Kremlin-Bicêtre, France, 2023), addressed these emergent questions and fostering a deeper understanding of the disease's multifaceted nature. These discussions were not limited to theoretical advancements but extended into the practical realms of patient management, highlighting the challenges and opportunities in applying the latest guidelines to clinical practice.

Pathophysiology of Heart Failure: A Role for Peripheral Blood Mononuclear Cells Mitochondrial Dysfunction?

Heart failure (HF) is a leading cause of hospitalization in patients aged more than 65 years and is associated with high mortality rates. A better comprehension of its physiopathology is still needed, and, in addition to neurohormonal systems and sodium glucose co-transporter 2 modulations, recent studies focus on the mitochondrial respiration of peripheral blood circulating cells (PBMCs). Thus, cardiovascular metabolic risk factors and cellular switch with an increased neutrophil/lymphocytes ratio might favor the decreased PBMC mitochondrial respiration observed in relation with HF severity. PBMCs are implicated in the immune system function and mitochondrial dysfunction of PBMC, potentially induced by their passage through a damaged heart and by circulating mitoDAMPs, which can lead to a vicious circle, thus sustaining negative cardiac remodeling during HF. This new approach of HF complex pathophysiology appears to be a promising field of research, and further studies on acute and chronic HF with reduced or preserved LVEF are warranted to better understand whether circulating PBMC mitochondrial function and mitoDAMPs follow-ups in HF patients might show diagnosis, prognosis or therapeutic usefulness.

Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units.

BACKGROUND: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention. METHOD: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry. RESULTS: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values. CONCLUSIONS: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.