Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.

AIM: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. METHODS: Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. RESULTS: There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho = - 0.528, P = 0.017 and Spearman's rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036). CONCLUSION: This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson's Disease-a Systematic Review.

PURPOSE OF REVIEW: The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent advancements in the field of the diagnosis and management of blood pressure abnormalities in these patients. Our goal was to guide physicians to avoid pitfalls in current practice while treating patients with Parkinson disease and blood pressure abnormalities. For this purpose, we searched bibliographic databases (PubMed, Google Scholar) for all publications published on blood pressure effects in Parkinson disease until May 2020. Furthermore, we highlight some thoughts and potential perspectives for the next possible steps in the field. RECENT FINDINGS: Blood pressure dysregulation in patients with Parkinson's disease has several implications in clinical practice and presents an ongoing concern. Compared with chronic essential hypertension, the syndrome of combined neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease has received little attention. If left untreated, hypertension may lead to cardiovascular disease whereas hypotension may lead to fall-related complications, with tremendous impact on the quality of life of affected individuals. The effect of blood Epressure control and the risk of death from cardiovascular disease in Parkinson disease are largely unexplored. Blood pressure abnormalities in Parkinson disease present bidirectional relationship and the rationale for treating and controlling hypertension in persons with Parkinson disease and concurrent neurogenic orthostatic hypotension and/or supine hypertension is compelling. Further research is warranted in order to clarify the mechanisms, clinical implications, and potential reversibility of compromised cardiovascular function, in persons with Parkinson disease.

Effects of Chemotherapy on Aortic 18-Fluorodeoxyglucose Uptake in Patients With Hodgkin and Non-Hodgkin Lymphoma.

Background: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. Results: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). Conclusions: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

The effect of an mRNA vaccine against COVID-19 on endothelial function and arterial stiffness.

To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients.

BACKGROUND AND AIMS: We aimed to investigate potential eligibility for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in patients with coronary artery disease and dyslipidaemia according to patient characteristics and variable criteria. METHODS: We prospectively enrolled 2000 patients (acute coronary syndrome = 407, chronic coronary artery disease inpatients = 1087, outpatient Lipid's clinic = 506). To calculate PCSK-9 inhibitors real-world eligibility, a proprietary adjustable software was developed, which stores data and patient characteristics and can determine eligibility depending on different criteria. We tested four scenarios with different LDL thresholds according to ESC/EAS 2016 and 2019 Guidelines, 2017 American College of Cardiology Expert Consensus, and National criteria. RESULTS: The eligible percentage was 18.85%, 9.75%, 8.55% and 2.15%, in the total population for the four classifications, respectively, and it varied according to clinical status. The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter. CONCLUSIONS: For the first time, a realistic estimation of PCSK-9 eligibility is provided via an adjustable predictive model in a population of 2000 patients with acute coronary syndrome, chronic coronary artery disease and dyslipidaemia. This can be a valuable tool for the incorporation of PCSK-9 inhibitors in health care systems.

Lymphoma Severity and Type Are Associated With Aortic FDG Uptake by 18F-FDG PET/CT Imaging.

BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Aortic wall stiffness as a side-effect of anti-cancer medication.

Introduction: Malignancies and cardiovascular disease are the two leading causes of mortality worldwide. There is a growing concern that anti-cancer drugs may lead to increased cardiovascular morbidity among cancer survivors. This may be the result of direct effects of the cancer treatment on heart function, or due to an indirect acceleration of atherosclerosis.Areas covered: We searched two bibliographic databases [PubMed, Scopus] and one full-text database (Google Scholar) for publications on chemotherapy and arterial stiffness since 1970. Anthracyclines, alkylating agents and tyrosine kinase inhibitors seem to affect arterial elastic properties. These effects can be non-reversible and may appear after treatment termination. Monoclonal antibodies may induce either a temporary increase or no change on arterial stiffness of patients with malignancies. Anti-microtubule agents and antimetabolites have not been extensively studied so far.Expert opinion: This literature review suggests that certain anticancer medications may impair arterial stiffness, and that assessment of arterial elastic properties before and after initiation of anti-neoplasmatic therapy may be clinically useful in order to develop protective strategies against chemotherapy-induced vascular effects. Further research is warranted to confirm the effects of anti-cancer agents on arterial stiffness, as well as their potential clinical implications. Future research lies in finding new targeted biomarkers identifying arterial stiffness such as micro RNAs while imaging techniques could also be implemented in assessment of vascular toxicity.

Clinical significance of pleural effusions and association with outcome in patients hospitalized with a first episode of acute pericarditis.

The clinical significance of pleural effusions (PLEs) in the setting of acute pericarditis remains poorly investigated. We sought to identify predictive factors for PLEs and their association with the short- and long-term prognosis of patients with acute pericarditis. We enrolled 177 patients hospitalized with a first episode of acute pericarditis. In all cases an extensive clinical, biochemical, and diagnostic work-up to detect PLEs and establish etiological diagnosis was performed. All patients included were prospectively followed for a maximum of 18 months (median 12, range 1-18) and complications were recorded. PLEs were detected in n = 94 cases (53.1% of the cohort; bilateral 53.2%, left-sided 28.7%, right-sided 18.1%) and were strongly associated with c-reactive protein (CRP) levels at admission (rho = 0.328, p < 0.001). In multivariate logistic regression, independent predictors for PLEs were female gender (OR = 2.46, 95% CI 1.03-5.83), age (per 1-year increment OR = 1.030, 95% CI 1.005-1.056), CRP levels (per 1 mg/L increment OR = 1.012, 95% CI 1.006-1.019) and size of pericardial effusion (per 1 cm increment, OR = 1.899, 95% CI 1.228-2.935). Bilateral PLEs were associated with increased risk for in-hospital cardiac tamponade (OR = 7.52, 95% CI 2.16-26.21). There was no association of PLEs with new onset atrial fibrillation or pericarditis recurrence during long-term follow-up (χ2 = 0.003, p = 0.958). We conclude that PLEs are common in patients hospitalized with a first episode of acute pericarditis. They are related to the intensity of inflammatory reaction, and they should not be considered necessarily as a marker of secondary etiology. Bilateral PLEs are associated with increased risk of in-hospital cardiac tamponade, but do not affect the long-term risk of pericarditis recurrence.