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COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiovascular Medicine".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 39013

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Prof. Dr. Jean-Sébastien Hulot

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Paris Cardiovascular Research Center, PARCC, INSERM UMR970, Paris, France
Interests: pathways leading to premature heart failure; pathological cardiac remodeling; biomarkers and omics; myocardial stiffening; pharmacology

Special Issue Information

Dear colleagues,

Since December 2019, the COVID-19 pandemic has spread all over the world, with more than one hundred million confirmed cases to date. Multiple studies have progressively highlighted the strong connections between COVID-19 and the cardiovascular system. On one hand, adults with previous heart conditions (such as heart failure, coronary artery disease or cardiomyopathies) or with underlying cardiometabolic factors (such as diabetes, obesity or hypertension) are at increased risk for severe forms of COVID-19. On the other hand, recent studies have suggested a particular tropism of SARS-CoV-2 for cardiovascular cells, especially for endothelial cells and, potentially, cardiomyocytes, and cardiovascular outcomes are frequently reported in patients with COVID-19.

In this Special Issue, we invite original research articles and state-of-the-art reviews focused on current knowledge and future perspectives on the interactions between SARS-CoV-2 and the cardiovascular system, including these important topics: risk stratification according to the cardiovascular profiles of patients; direct vs. indirect mechanisms supporting cardiovascular injuries in COVID-19 patients; the diagnosis of cardiovascular injury; specific therapeutic approaches in COVID-19 patients according to cardiovascular involvement; the long-term cardiovascular effects of COVID-19.

Prof. Dr. Jean-Sébastien Hulot
Guest Editor

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Keywords

COVID-19
SARS-CoV-2
cardiovascular
myocardium
endothelium
risk factors
pathophysiology
therapeutic perspectives
prognosis
biomarkers

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Published Papers (10 papers)

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Research

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12 pages, 547 KiB

Open AccessArticle

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation

by Kuk Hui Son, Woong-Han Kim, Jae Gun Kwak, Chang-Hyu Choi, Seok In Lee, Ui Won Ko, Hyoung Soo Kim, Haeyoung Lee, Euy Suk Chung, Jae-Bum Kim, Woo Sung Jang, Jae Seung Jung, Jieon Kim, Young Kyung Yoon, Seunghwan Song, Minji Sung, Myung Hun Jang, Young Sam Kim, In-Seok Jeong, Do Wan Kim, Tae Yun Kim, Soon Jin Kim, Su Wan Kim, Joonhwa Hong, Hyungmi An and on behalf of The Korean Society for Thoracic and Cardiovascular Surgery COVID-19 ECMO Task Force Team Show full author list Hide full author list

J. Clin. Med. 2022, 11(17), 5106; https://doi.org/10.3390/jcm11175106 - 30 Aug 2022

Cited by 3 | Viewed by 1909

Abstract

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged ≥19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) < 18.5 kg/m². Glucose at admission >200 mg/dL and glucose levels before ventilator >200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO >200 mg/dL and minimal glucose levels during hospitalization <70 mg/dL were associated with in-hospital mortality. Multivariable Cox regression analysis showed that glucose >200 mg/dL before ECMO and minimal glucose <70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose >200 mg/dL before ECMO and minimal glucose level <70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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12 pages, 848 KiB

Open AccessArticle

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19

by Giulia Renda, Fabrizio Ricci, Enrico Guido Spinoni, Leonardo Grisafi, Damiano D’Ardes, Marco Mennuni, Claudio Tana, Andrea Rognoni, Mattia Bellan, Pier Paolo Sainaghi, Mario Pirisi, Simona De Vecchi, Sabina Gallina, Sante Donato Pierdomenico, Francesco Cipollone and Giuseppe Patti

J. Clin. Med. 2022, 11(3), 729; https://doi.org/10.3390/jcm11030729 - 29 Jan 2022

Cited by 16 | Viewed by 2867

Abstract

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01–1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05–6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19–10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13–8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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10 pages, 718 KiB

Open AccessArticle

Myocardial Injury as a Prognostic Factor in Mid- and Long-Term Follow-Up of COVID-19 Survivors

by Andrea Izquierdo, Diana Mojón, Alfredo Bardají, Anna Carrasquer, Alicia Calvo-Fernández, José Carreras-Mora, Teresa Giralt, Sílvia Pérez-Fernández, Núria Farré, Cristina Soler, Clàudia Solà-Richarte, Paula Cabero, Beatriz Vaquerizo, Jaume Marrugat and Núria Ribas

J. Clin. Med. 2021, 10(24), 5900; https://doi.org/10.3390/jcm10245900 - 16 Dec 2021

Cited by 14 | Viewed by 2939

Abstract

Myocardial injury, which is present in >20% of patients hospitalized for COVID-19, is associated with increased short-term mortality, but little is known about its mid- and long-term consequences. We evaluated the association between myocardial injury with one-year mortality and readmission in 172 COVID-19 patients discharged alive. Patients were grouped according to the presence or absence of myocardial injury (defined by hs-cTn levels) on admission and matched by age and sex. We report mortality and hospital readmission at one year after admission in all patients and echocardiographic, laboratory and clinical data at six months in a subset of 86 patients. Patients with myocardial injury had a higher prevalence of hypertension (73.3% vs. 50.0%, p = 0.003), chronic kidney disease (10.5% vs. 2.35%, p = 0.06) and chronic heart failure (9.3% vs. 1.16%, p = 0.03) on admission. They also had higher mortality or hospital readmissions at one year (11.6% vs. 1.16%, p = 0.01). Additionally, echocardiograms showed thicker walls in these patients (10 mm vs. 8 mm, p = 0.002) but without functional disorder. Myocardial injury in COVID-19 survivors is associated with poor clinical prognosis at one year, independent of age and sex, but not with echocardiographic functional abnormalities at six months. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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11 pages, 963 KiB

Open AccessArticle

Biomarkers Predict In-Hospital Major Adverse Cardiac Events in COVID-19 Patients: A Multicenter International Study

by Michael Y. Henein, Giulia Elena Mandoli, Maria Concetta Pastore, Nicolò Ghionzoli, Fouhad Hasson, Muhammad K. Nisar, Mohammed Islam, Francesco Bandera, Massimiliano M. Marrocco-Trischitta, Irene Baroni, Alessandro Malagoli, Luca Rossi, Andrea Biagi, Rodolfo Citro, Michele Ciccarelli, Angelo Silverio, Giulia Biagioni, Joseph A. Moutiris, Federico Vancheri, Giovanni Mazzola, Giulio Geraci, Liza Thomas, Mikhail Altman, John Pernow, Mona Ahmed, Ciro Santoro, Roberta Esposito, Guillem Casas, Rubén Fernández-Galera, Maribel Gonzalez, Jose Rodriguez Palomares, Ibadete Bytyçi, Frank Lloyd Dini, Paolo Cameli, Federico Franchi, Gani Bajraktari, Luigi Paolo Badano and Matteo Cameli Show full author list Hide full author list

J. Clin. Med. 2021, 10(24), 5863; https://doi.org/10.3390/jcm10245863 - 14 Dec 2021

Cited by 9 | Viewed by 4971

Abstract

Background: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19. Methods: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE). Results: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan–Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001). Conclusions: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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10 pages, 2964 KiB

Open AccessArticle

Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome

by Amaya Jimeno-Almazán, Jesús G. Pallarés, Ángel Buendía-Romero, Alejandro Martínez-Cava and Javier Courel-Ibáñez

J. Clin. Med. 2021, 10(22), 5434; https://doi.org/10.3390/jcm10225434 - 20 Nov 2021

Cited by 17 | Viewed by 6455

Abstract

Patients recovering from COVID-19 commonly report persistence of dyspnea, exertional fatigue, and difficulties in carrying out their daily activities. However, the nature of these symptoms is still unknown. The purpose of the study was to identify limiting causes of cardiopulmonary origin for the performance of physical exercise in post-COVID-19 condition that could explain the symptomatic persistence of dyspnea or fatigue-related symptoms. Thirty-two non-hospitalized patients with post-COVID-19 condition (i.e., still presenting a chronic symptomatic phase lasting >90 days since debut of symptoms that lasted for at least 2 months and cannot be explained by an alternative diagnosis) completed a clinical examination including echocardiography, submaximal and maximal cardiorespiratory fitness tests (Ekblom-Bak and Bruce’s protocols), and a battery of validated questionnaires about fatigue and exercise intolerance. Four participants (12.5%) reported an abnormal cardiac response to exercise during the submaximal test, which aroused suspicion of the presence of chronotropic incompetence. All of them were confirmed with a positive diagnosis maximal exercise test after cardiology screening, even with a comprehensive clinical examination, resting ECG, and echocardiogram, without other findings. No statistical differences were found in any physiological variables or questionnaire values, between patients with positive and negative diagnoses. Chronotropic incompetence and other autonomic disorders may appear in patients with mild forms of COVID-19 presentation and may persist in the long term, being responsible for exercise intolerance after resolution of acute infection. Clinicians should be aware that chronotropic incompetence and other autonomic disorders may be a complication of COVID-19 and should consider appropriate diagnostic and therapeutic interventions in these patients, especially when early exercise-related fatigability is reported. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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12 pages, 3721 KiB

Open AccessArticle

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia

by Antoine Fayol, Marine Livrozet, Héléna Pereira, Jean-Luc Diehl, David Lebeaux, Jean-Benoit Arlet, Bernard Cholley, Claire Carette, Jean-Baptiste Carves, Sébastien Czernichow, Caroline Hauw, Sophie-Rym Hamada, Anne-Sophie Jannot, Geoffroy Volle, Nihar Masurkar, Tristan Mirault, Benjamin Planquette, Olivier Sanchez, Gilles Châtellier, Michel Azizi and Jean-Sébastien Hulot Show full author list Hide full author list

J. Clin. Med. 2021, 10(19), 4618; https://doi.org/10.3390/jcm10194618 - 8 Oct 2021

Cited by 4 | Viewed by 2428

Abstract

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24–4.09; p = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12–4.03; p = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24–0.64; p = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11–0.56; p = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32–0.91; p = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% p < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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10 pages, 3437 KiB

Open AccessArticle

Long COVID: Distinction between Organ Damage and Deconditioning

by Johannes Kersten, Michael Baumhardt, Paul Hartveg, Luis Hoyo, Elina Hüll, Armin Imhof, Cornelia Kropf-Sanchen, Nicoleta Nita, Johannes Mörike, Manuel Rattka, Stefanie Andreß, Dominik Scharnbeck, Gerlinde Schmidtke-Schrezenmeier, Marijana Tadic, Alexander Wolf, Wolfgang Rottbauer and Dominik Buckert

J. Clin. Med. 2021, 10(17), 3782; https://doi.org/10.3390/jcm10173782 - 24 Aug 2021

Cited by 28 | Viewed by 4924

Abstract

(1) Background: Long COVID syndrome refers to long-term sequelae of the novel viral disease, which occur even in patients with initially mild disease courses. However, there is still little evidence of the actual organic consequences and their frequency, and there is no standardized workup to diagnose long COVID syndrome yet. In this study, we aim to determine the efficiency of a stepwise diagnostic approach for reconvalescent COVID-19 patients with cardiopulmonary symptoms. (2) Methods: The diagnostic workup for long COVID syndrome included three steps. In the first step, the focus was on broad applicability (e.g., blood tests and body plethysmography). In the second step, cardiopulmonary exercise testing (CPET) and cardiac MRI (CMR) were used. The third step was tailored to the individual needs of each patient. The observation period lasted from 22 February to 14 May 2021. (3) Results: We examined 231 patients in our long COVID unit (mean [SD] age, 47.8 [14.9], 132 [57.1%] women). Acute illness occurred a mean (SD) of 121 (77) days previously. Suspicious findings in the first visit were seen in 80 (34.6%) patients, prompting further diagnostics. Thirty-six patients were further examined with CPET and CMR. Of those, 16 (44.4%) had pathological findings. The rest had functional complaints without organ damage (“functional long COVID”). Cardiopulmonary sequelae were found in asymptomatic as well as severe courses of the initial COVID-19 disease. (4) Conclusions: A structured diagnostic pathway for the diagnosis of long COVID syndrome is practicable and rational in terms of resource allocation. With this approach, manifest organ damage can be accurately and comprehensively diagnosed and distinguished from functional complaints. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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13 pages, 18423 KiB

Open AccessArticle

Early Echocardiographic and Cardiac MRI Findings in Multisystem Inflammatory Syndrome in Children

by Domenico Sirico, Alessia Basso, Elena Reffo, Annachiara Cavaliere, Biagio Castaldi, Jolanda Sabatino, Alessandra Meneghel, Giorgia Martini, Liviana Da Dalt, Francesco Zulian and Giovanni Di Salvo

J. Clin. Med. 2021, 10(15), 3360; https://doi.org/10.3390/jcm10153360 - 29 Jul 2021

Cited by 42 | Viewed by 4637

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a known severe condition affecting children previously exposed to SARS-CoV-2. The aim of our study was to describe the early cardiac abnormalities in patients with MIS-C, evaluated by speckle tracking echocardiography (STE) and cardiac MRI (CMR). Clinical, laboratory and microbiological data were measured for all patients. All children underwent standard transthoracic echocardiography, STE with analysis of left ventricle global longitudinal strain (GLS). Seventeen (75%) of the children were evaluated with CMR. Twenty-three patients (13M, 10F) were recruited, mean age was 8.1 ± 4 years. Cardiovascular symptoms were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission. In-hospital survival was 100%. TnI was elevated in 15 (65.2%) and BNP in 20 (86.9%) patients. The median time to STE evaluation was 8 days and to CMR was 18 days after fever onset. Mean LVEF was 59 ± 10%. Coronary dilation was observed in six (26.1%) patients. STE showed a reduced mean LVGLS (−17 ± 4.3%). LGE with a non-ischemic pattern was evident in six out of seventeen patients (35.2%). The elevation of myocardial necrosis markers, the reduction of LVGLS and the presence of LGE on CMR in about a quarter of MIS-C patients supports the hypothesis of a post-viral immune-mediated myocarditis-like pathogenesis. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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Review

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15 pages, 1013 KiB

Open AccessReview

The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme

by Riccardo Sarzani, Massimiliano Allevi, Federico Giulietti, Chiara Di Pentima, Serena Re, Piero Giordano and Francesco Spannella

J. Clin. Med. 2021, 10(24), 5883; https://doi.org/10.3390/jcm10245883 - 15 Dec 2021

Cited by 3 | Viewed by 3130

Abstract

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the “classic” renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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14 pages, 6664 KiB

Open AccessReview

The Link between SARS-CoV-2 Infection, Inflammation and Hypercoagulability-Impact of Hemorheologic Alterations on Cardiovascular Mortality

by Johanna Sandor-Keri, Istvan Benedek, Stefania Polexa and Imre Benedek

J. Clin. Med. 2021, 10(14), 3015; https://doi.org/10.3390/jcm10143015 - 6 Jul 2021

Cited by 11 | Viewed by 3311

Abstract

The link between severe forms of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and cardiovascular diseases has been well documented by various studies that indicated a higher risk of cardiovascular complications in COVID-19 patients, in parallel with a higher risk of mortality in COVID-19 patients with underlying cardiovascular diseases. It seems that inflammation, which is a major pathophysiological substrate for both acute myocardial infarction and severe forms of COVID-19, may play a pivotal role in the interrelation between these two critical conditions, and hypercoagulability associated with SARS-CoV-2 infection could be responsible for acute cardiovascular complications. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) proved to be independent predictors for prognosis in acute coronary syndromes and systemic inflammatory diseases; therefore, they may be used as independent prognostic markers of disease severity in COVID-19 infection. The aim of this review is to present the most recent advances in understanding the complex link between SARS-CoV-2 infection, inflammation and alteration of blood coagulability and hemorheology, leading to major cardiovascular events. Full article

(This article belongs to the Special Issue COVID-19 and the Cardiovascular System: Implications for Risk Assessment, Diagnosis, and Treatment Options)

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