Background: Cardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. Methods: We studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR). Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. Results: Median age was 52 years (IQR 41–57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3–11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4 ^- CD8 ^-/lo Tαβ-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4 ^- CD8 ^-/lo Tαβ-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). Conclusions: Pericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response. The trial is registered with ClinicalTrials.gov, number NCT04413071 Research in context: Evidence before this study: Very little evidence exists describing long cardiac sequelae after SARS-CoV-2 infection. Although pericarditis and myocarditis are the two most frequent cardiac manifestations observed after a viral infection, as of May 13, 2020, the peer-reviewed literature was limited to isolated case reports of myocarditis and pericarditis during the COVID-19 hospitalization phase and to a retrospective observation in 26 recovered patients with COVID-19 pneumonia presenting cardiac complaints during hospitalization, revealing the presence of myocardial oedema in 14 (54%) patients and late gadolinium enhancement in 8 (31%) patients. These small size case series, limited to hospitalized RT-PCR patients with COVID-19 pneumonia, are insufficient to generalize conclusions about the true prevalence of pericardial and myocardial long involvement after SARS-CoV-2 infection. In addition, no study has investigated the immunological consequences of SARS-CoV-2 infection in the settings of pericarditis and myocarditis. Added value of this study: To our knowledge, this is the largest cohort of subjects (N=139) —even for other common viruses— with clinical, electrocardiographic, laboratory and CMR imaging evaluations, to assess pericardial and myocardial involvements after SARS-CoV-2 infection. The strength of this study is the addition of non-hospitalized participants and also the inclusion of participants diagnosed of past SARS-CoV-2 infection through serology. Contrary to previous studies, women are well represented. We found a prevalence of pericarditis or myocarditis up to 40% cases; pericarditis coexisted with some degree of concurrent myocardial inflammation in 11% cases. Study participants who were previously hospitalized for COVID-19 pneumonia and patients who received antiviral (hydroxychloroquine, lopinavir-ritonavir) or anti-inflammatory (high-dose glucocorticoids and anti-interleukin treatments) treatments, and who were on chronic drug treatment with statins, were less likely to develop pericarditis or myocarditis. The clinical assessment of the participants showed clinical stability without any patient presenting severe pericardial effusion, heart failure or left ventricular dysfunction. We provide new data on seropositive subjects; although RT-PCR participants were more likely to still present symptoms than participants diagnosed by serology, the prevalence of pericarditis, myocarditis or myocarditis, almost three months after the initial viral prodrome, was high in both groups. In-depth investigation of the distribution of multiple major and minor populations of immune cells in blood showed high frequency of altered immune profiles after SARS-CoV-2 infection. The altered immune cell profiles identified partially mimic abnormalities previously reported during active infection together with others described here for the first time, with unique patterns associated with pericardial and/or myocardial injury. Nonetheless, we also described altered immune profiles in participants without pericardial and myocardial manifestations. Whether these later alterations are due to persistence of tissue damage in other organs affected by SARS-CoV-2, such as the lung, or they reflect normal post-infection immune recovery mechanisms, remains to be investigated. Implications of all the available evidence: At present, there is much interest in the long-term sequelae of COVID-19. It is intriguing that pericarditis and myocarditis were observed so long after SARS-CoV-2 infection and also in some presently asymptomatic subjects, in association with notably altered immune cell profiles in blood. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late, paving the way for a better understanding the immune mechanisms involved. Thus, our study may have health-care consequences given the widespread diagnosis of SARS-CoV-2 infection in population-based seroprevalence studies.

In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes. As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m² or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination. A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019). The E:e’ ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e’ ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients.

Introducción y objetivos: Las secuelas cardiacas tras la infección por SARS-CoV-2 todavía están poco documentadas. Se realizó un estudio transversal en trabajadores sanitarios para estudiar la prevalencia de afección pericárdica y miocárdica tras la infección por SARS-CoV-2. Métodos: Se estudió a 139 trabajadores sanitarios con infección previa por SARS-CoV-2 confirmada. Los participantes se sometieron a evaluación clínica, electrocardiograma, pruebas de laboratorio que incluyeron el perfil de células inmunitarias y resonancia magnética cardiaca (RMC). El diagnóstico clínico de pericarditis se realizó según los criterios clásicos y el diagnóstico clínico de miocarditis, ante la presencia de al menos 2 criterios en la RMC. Resultados: La mediana de edad fue 52 (intervalo, 41-57) años, el 71,9% eran mujeres y el 16,5% se había hospitalizado previamente por neumonía por COVID-19. En la evaluación (10,4 [9,3-11,0] semanas después de los síntomas de infección), todos los participantes presentaban estabilidad hemodinámica. El 41,7% tenía dolor torácico, disnea o palpitaciones; el 49,6%, alteraciones electrocardiográficas; el 7,9%, elevación de NT-proBNP; el 0,7%, elevación de troponina y el 60,4%, alteraciones en la RMC. El 30,9% de los participantes cumplían los criterios clínicos establecidos de pericarditis o miocarditis: pericarditis aislada en el 5,8%, miopericarditis en el 7,9% y miocarditis aislada en el 17,3%. La mayoría de los participantes (73,2%) mostraron recuentos alterados de células inmunitarias en sangre, en particular diminución de eosinófilos (27,3%; p < 0,001) y aumento del número de células T citotóxicas (17,3%; p < 0,001). La sospecha clínica de pericarditis se asoció (p < 0,005) particularmente con un elevado número de células T citotóxicas y recuento de eosinófilos disminuido, mientras que los participantes con sospecha clínica de miopericarditis o miocarditis tenían recuentos de neutrófilos, células natural killer y células plasmáticas más bajos (p < 0,05). Conclusiones: La afección pericárdica y miocárdica con estabilidad hemodinámica es frecuente después de la infección por SARS-CoV-2 y se asocia con perfiles de células inmunitarias específicas. Introduction and objectives The cardiac sequelae of SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in healthcare workers to report evidence of pericardial and myocardial involvement after SARS-CoV-2 infection. Methods We studied 139 healthcare workers with confirmed past SARS-CoV-2 infection. Participants underwent clinical assessment, electrocardiography, and laboratory tests, including immune cell profiling and cardiac magnetic resonance (CMR). Clinically suspected pericarditis was diagnosed when classic criteria were present and clinically suspected myocarditis was based on the combination of at least 2 CMR criteria. Results Median age was 52 (41-57) years, 71.9% were women, and 16.5% were previously hospitalized for COVID-19 pneumonia. On examination (10.4 [9.3-11.0] weeks after infection-like symptoms), participants showed hemodynamic stability. Chest pain, dyspnea or palpitations were present in 41.7% participants, electrocardiographic abnormalities in 49.6%, NT-proBNP elevation in 7.9%, troponin in 0.7%, and CMR abnormalities in 60.4%. A total of 30.9% participants met criteria for either pericarditis and/or myocarditis: isolated pericarditis was diagnosed in 5.8%, myopericarditis in 7.9%, and isolated myocarditis in 17.3%. Most participants (73.2%) showed altered immune cell counts in blood, particularly decreased eosinophil (27.3%; P < .001) and increased cytotoxic T cell numbers (17.3%; P < .001). Clinically suspected pericarditis was associated (P < .005) with particularly elevated cytotoxic T cells and decreased eosinophil counts, while participants diagnosed with clinically suspected myopericarditis or myocarditis had lower (P < .05) neutrophil counts, natural killer-cells, and plasma cells. Conclusions Pericardial and myocardial involvement with clinical stability are frequent after SARS-CoV-2 infection and are associated with specific immune cell profiles.

Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70–93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14–96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.

Background: Right ventricular (RV) to pulmonary circulation (PC) coupling can stratify prognosis in heart failure (HF). In this study, we assessed the prognostic role of the mean velocity of the pulmonary artery (mvPA) determined by cardiac magnetic resonance (CMR) in HF with preserved ejection fraction (HFpEF). Methods: Inclusion of 58 HFpEF outpatients that underwent CMR with measurement of RV–PC coupling parameters including mvPA between 2016 and 2019. The primary combined endpoint was a composite of HF readmissions and all-cause mortality. Results: Optimal cut-off value of mvPA calculated by receiver operating curve for the prediction of the primary endpoint was 9 cm/s. Over a median follow-up of 23 months (interquartile range: 24), 21 patients met the primary endpoint. The primary endpoint was more frequent in patients with mvPA ≤ 9 cm/s, as indicated by Kaplan–Meier survival curves; Log-Rank: 9.193, p = 0.02, regardless of RV dysfunction. On Cox multivariate analysis, mvPA ≤ 9 cm/s emerged as an independent prognostic predictor of the primary endpoint (HR: 4.11, 95% CI: 1.28–13.19, p = 0.017), together with left atrial area by CMR (HR: 1.08, 95% CI: 1.01–1.24, p = 0.034). Conclusions: In our HFpEF cohort, mvPA was associated with a higher rate of the primary endpoint, regardless of RV function, thus enabling identification of patients at higher risk of cardiovascular events before structural damage onset.

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients.