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1.
J Clin Ultrasound ; 51(4): 613-621, 2023 May.
Article in English | MEDLINE | ID: covidwho-2301433

ABSTRACT

INTRODUCTION: Cardiac injury is commonly reported in COVID-19 patients, resulting associated to pre-existing cardiovascular disease, disease severity, and unfavorable outcome. Aim is to report cardiac magnetic resonance (CMR) findings in patients with myocarditis-like syndrome during the acute phase of SARS-CoV-2 infection (AMCovS) and post-acute phase (cPACS). METHODS: Between September 2020 and January 2022, 39 consecutive patients (24 males, 58%) were referred to our department to perform a CMR for the suspicion of myocarditis related to AMCovS (n = 17) and cPACS (n = 22) at multimodality evaluation (clinical, laboratory, ECG, and echocardiography). CMR was performed for the assessment of volume, function, edema and fibrosis with standard sequences and mapping techniques. CMR diagnosis and the extension and amount of CMR alterations were recorded. RESULTS: Patients with suspected myocarditis in acute and post-COVID settings were mainly men (10 (59%) and 12 (54.5%), respectively) with older age in AMCovS (58 [48-64]) compared to cPACS (38 [26-53]). Myocarditis was confirmed by CMR in most of cases: 53% of AMCovS and 50% of cPACS with negligible LGE burden (3 [IQR, 1-5] % and 2 [IQR, 1-4] %, respectively). Myocardial infarction was identified in 4/17 (24%) patients with AMCovS. Cardiomyopathies were identified in 12% (3/17) and 27% (6/22) of patients with AMCovS and cPACS, including DCM, HCM and mitral valve prolapse. CONCLUSIONS: In patients with acute and post-acute COVID-19 related suspected myocarditis, CMR improves diagnostic accuracy characterizing ischemic and non-ischemic injury and unraveling subclinical cardiomyopathies.


Subject(s)
COVID-19 , Cardiomyopathies , Myocarditis , Male , Humans , Female , Myocarditis/complications , Myocarditis/diagnostic imaging , COVID-19/complications , Predictive Value of Tests , SARS-CoV-2 , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Contrast Media
2.
Circ Res ; 132(4): 483-497, 2023 02 17.
Article in English | MEDLINE | ID: covidwho-2300453

ABSTRACT

Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells' environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.


Subject(s)
Cardiomyopathies , Heart Diseases , Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Animals , Humans , Heart Diseases/therapy , Heart Diseases/metabolism , Myocytes, Cardiac/metabolism , Cardiomyopathies/metabolism , Pluripotent Stem Cells/metabolism , Lab-On-A-Chip Devices
3.
Int J Mol Sci ; 24(7)2023 Mar 30.
Article in English | MEDLINE | ID: covidwho-2299235

ABSTRACT

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.


Subject(s)
COVID-19 , Cardiomyopathies , MicroRNAs , Myocardial Ischemia , Humans , Systems Biology , Molecular Docking Simulation , Vindesine , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2 , Computational Biology , Myocardial Ischemia/epidemiology , Myocardial Ischemia/genetics , Comorbidity , MicroRNAs/genetics , Biomarkers , Transcription Factors , Gene Expression Profiling
4.
Monaldi Arch Chest Dis ; 92(1)2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-2276235

ABSTRACT

We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.


Subject(s)
COVID-19 , Cardiomyopathies , Heart Failure , Hypertension , Myocarditis , COVID-19/complications , Cardiomyopathies/diagnosis , Cardiomyopathies/diagnostic imaging , Heart Failure/diagnosis , Heart Failure/etiology , Humans , Hypertension/complications , Male , Myocarditis/diagnostic imaging , Myocarditis/etiology
5.
Kardiologiia ; 62(12): 80-84, 2022 Dec 31.
Article in Russian | MEDLINE | ID: covidwho-2260289

ABSTRACT

A 37-year-old female patient was admitted 16 days after delivery in a hospital for infectious diseases with cough, shortness of breath, and infiltrative changes in the lungs that were interpreted as viral pneumonia. Considering the failure of therapy and the history, peripartum cardiomyopathy was suspected. Examination revealed a decrease in left ventricular ejection fraction to 30 %, ultrasonic signs of lung congestion and bilateral hydrothorax. The patient was diagnosed with peripartum cardiomyopathy accompanied by functional class 4 heart failure. A specific feature of this case was fast positive dynamics with complete regression of the clinical picture of congestion and improvement of the left ventricular myocardial function associated with the treatment.


Subject(s)
COVID-19 , Cardiomyopathies , Pregnancy Complications, Cardiovascular , Puerperal Disorders , Female , Humans , Adult , Pregnancy , Stroke Volume , Ventricular Function, Left , Peripartum Period , COVID-19/complications , COVID-19/diagnosis , Cardiomyopathies/complications , Cardiomyopathies/diagnosis , Puerperal Disorders/diagnosis , Puerperal Disorders/etiology , Lung , Diagnostic Errors , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/therapy
6.
Pediatr Int ; 64(1): e15317, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-2251024

ABSTRACT

BACKGROUND: Mitochondrial fatty acid oxidation disorders (FAODs) cause impairment in energy metabolism and can lead to a spectrum of cardiac pathologies including cardiomyopathy and arrhythmias. The frequency of underlying cardiac pathologies and the response to recommended treatment in FAODs was investigated. METHODS: Sixty-eight children (35 males, 33 females) with the diagnosis of a FAOD were included in the study. Cardiac function was evaluated with 12-lead standard electrocardiography, echocardiography, and 24 h Holter monitoring. RESULTS: Forty-five patients (66%) were diagnosed after disease symptoms developed and 23 patients (34%) were diagnosed in the pre-symptomatic period. Among symptomatic patients (n: 45), cardiovascular findings were detected in 18 (40%) patients, including cardiomyopathy in 14 (31.1%) and conduction abnormalities in 4 (8.8%) patients. Cardiac symptoms were more frequently detected in primary systemic carnitine deficiency (57.1%). Patients with multiple acyl-CoA dehydrogenase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and mitochondrial trifunctional protein deficiencies also had an increased frequency of cardiac symptoms. Patients with medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and carnitine palmitoyltransferase I deficiencies had a lower prevalence of cardiac symptoms both during admission and during clinical follow up. Cardiomyopathy resolved completely in 8/14 (57%) patients and partially in 2/14 (14.3%) patients with treatment. Two patients with cardiomyopathy died in the newborn period; cardiomyopathy persisted in 1 (7.1%) patient with very long-chain acyl-CoA dehydrogenase deficiency. CONCLUSION: Early diagnosis, treatment and follow up made a significant contribution to the improvement of cardiac symptoms of patients with FAODs.


Subject(s)
Cardiomyopathies , Lipid Metabolism, Inborn Errors , Mitochondrial Diseases , Child , Infant, Newborn , Male , Female , Humans , Lipid Metabolism, Inborn Errors/diagnosis , Acyl-CoA Dehydrogenase, Long-Chain/metabolism , Acyl-CoA Dehydrogenase , Mitochondrial Diseases/diagnosis , Cardiomyopathies/diagnosis , Fatty Acids , Carnitine , Oxidation-Reduction
7.
Card Electrophysiol Clin ; 14(3): 517-532, 2022 09.
Article in English | MEDLINE | ID: covidwho-2229044

ABSTRACT

"Despite being one of the best understood cardiac arrhythmias, the clinical meaning of atrial flutter varies according to the specific context, and its optimal treatment may be limited by both the suboptimal response to rate/rhythm control drugs and by the complexity of the underlying substrate. In this article, we present a state-of-the-art overview of mechanisms, prognostic impact, and medical/interventional management options for atrial flutter in several specific patient populations, including heart failure, cardiomyopathies, muscular dystrophies, posttransplant patients, patients with respiratory disorders, athletes, and subjects with preexcitation, aiming to stimulate further research in this challenging field and facilitate appropriate patient care."


Subject(s)
Atrial Fibrillation , Atrial Flutter , Cardiomyopathies , Catheter Ablation , Atrial Fibrillation/surgery , Humans
8.
J Am Heart Assoc ; 12(4): e027619, 2023 02 21.
Article in English | MEDLINE | ID: covidwho-2237732

ABSTRACT

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine-related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine-related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P<0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% (P<0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.


Subject(s)
Cardiomyopathies , Magnetocardiography , Myocarditis , Young Adult , Humans , Female , Middle Aged , Male , Myocarditis/diagnosis , Myocarditis/therapy , Magnetocardiography/methods , Stroke Volume , Ventricular Function, Left , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy
9.
J Heart Lung Transplant ; 42(4): 447-450, 2023 04.
Article in English | MEDLINE | ID: covidwho-2230368

ABSTRACT

Evidence on characteristics and outcomes of patients undergoing heart transplantation for coronavirus disease 2019 (COVID-19) associated cardiomyopathy is limited to case reports. Of all 6,332 patients aged ≥18 years undergoing heart transplantation from July 2020 through May 2022 in the United Network for Organ Sharing database, 12 (0.2%) patients had COVID-19 myocarditis and 98 (1.6%) patients with the same level of care had non-COVID-19 myocarditis. Their median age was 49 (range 19-74) years. All patients were hospitalized in the intensive care unit and 92.7% (n = 102) were on life support prior to transplantation. No patients with COVID-19 myocarditis required ventilation while waitlisted. Survival free from graft failure was 100% among COVID-19 patients and 88.5% among non-COVID-19 patients at a median of 257 (range 0-427) days post-transplant. These findings indicate that transplantation is rarely performed for COVID-19 related cardiomyopathy in the United States, yet early outcomes appear favorable in select patients.


Subject(s)
COVID-19 , Cardiomyopathies , Heart Transplantation , Adult , Aged , Humans , Middle Aged , Young Adult , Cardiomyopathies/epidemiology , Cardiomyopathies/etiology , Cardiomyopathies/surgery , COVID-19/complications , COVID-19/epidemiology , Heart Transplantation/adverse effects , Heart Transplantation/statistics & numerical data , Muscular Diseases/complications , Myocarditis/etiology , Myocarditis/surgery , Treatment Outcome , United States/epidemiology
10.
Int J Cardiovasc Imaging ; 39(5): 887-894, 2023 May.
Article in English | MEDLINE | ID: covidwho-2174492

ABSTRACT

BACKGROUND: Many patients who have recovered from their coronavirus disease 2019 (COVID-19) episode continue to remain symptomatic and seek medical opinion. The clinical characteristics and echocardiography findings of such subjects have not been adequately studied. METHODS: The study included 472 subjects (age 54.0 ± 13.4 years, 57% men) with previous COVID-19 (median duration since COVID-19 12.0 weeks, interquartile range 9.0-26.0 weeks) and 100 controls (age 53.9 ± 13.6 years, 53% men). All subjects underwent detailed clinical assessment and echocardiography, including measurement of left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS). RESULTS: Less than third (29.2%) of the post-COVID subjects had needed hospitalization for their initial infection. Exertional dyspnea or breathing difficulty at rest were the commonest reasons for post-COVID presentation. As compared to controls, the post-COVID subjects had impaired LV systolic (LVEF 63.2 ± 2.2 vs. 61.9 ± 4.6, P = 0.007; GLS - 19.9 ± 2.6% vs. -17.6 ± 3.4%, P < 0.001) and diastolic function. Majority of those with reduced LV GLS had preserved LVEF. The patients presenting before 12 weeks were more likely to be symptomatic, but LV GLS did not differ. The patients needing hospitalization had higher burden of co-morbidities and significantly reduced LV GLS as compared to those who had received domiciliary treatment. The patients in the lowest GLS tertile were older, had higher burden of co-morbidities, and had had more severe initial infection with greater need for hospitalization, oxygen therapy and steroids. The need for hospitalization was independently associated with lower GLS at the time of current presentation. CONCLUSION: This study shows that impairment of LV systolic and diastolic function is common among subjects recovering from previous COVID-19 episode. The patients with more severe initial infection have more marked impairment of LV function and this impairment persists even after several months of recovery from the initial infection. Routine measurement of GLS may be helpful since LV systolic dysfunction in these patients is mostly subclinical.


Subject(s)
COVID-19 , Cardiomyopathies , Ventricular Dysfunction, Left , Male , Humans , Infant , Female , Predictive Value of Tests , Ventricular Function, Left , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
12.
J Am Heart Assoc ; 11(20): e025844, 2022 10 18.
Article in English | MEDLINE | ID: covidwho-2079124

ABSTRACT

Background Cardiovascular complications from COVID-19 contribute to its high morbidity and mortality. The effect of COVID-19 infection on the coronary vasculature is not known. The objective of this study was to investigate the prevalence of coronary vasomotor dysfunction identified by coronary flow reserve from cardiac positron emission tomography in patients with previous COVID-19 infection. Methods and Results All patients who had polymerase chain reaction-confirmed SARS-CoV-2 infection referred for myocardial stress perfusion positron emission tomography imaging at Brigham and Women's Hospital from April 2020 to July 2021 were compared with a matched control group without prior SARS-CoV-2 infection imaged in the same period. The main outcome was the prevalence of coronary vasomotor dysfunction. Myocardial perfusion and myocardial blood flow reserve were quantified using N13-ammonia positron emission tomography imaging. Thirty-four patients with prior COVID-19 were identified and compared with 103 matched controls. The median time from polymerase chain reaction-confirmed SARS-CoV-2 to cardiac positron emission tomography was 4.6 months (interquartile range,1.2-5.6 months). There were 16 out of 34 (47%) patients previously hospitalized for COVID-19 infection. Baseline cardiac risk factors were common, and 18 (53%) patients in the COVID-19 group had abnormal myocardial perfusion. Myocardial blood flow reserve was abnormal (<2) in 44.0% of the patients with COVID-19 compared with 11.7% of matched controls (P<0.001). The mean myocardial blood flow reserve was 19.4% lower in patients with COVID-19 compared with control patients (2.00±0.45 versus 2.48±0.47, P<0.001). Conclusions Myocardial blood flow reserve was impaired in patients with prior COVID-19 infection compared with cardiovascular risk factor-matched controls, suggesting a relationship between SARS-CoV-2 infection and coronary vascular health. These data highlight the need to assess long-term consequences of COVID-19 on vascular health in future prospective studies.


Subject(s)
COVID-19 , Cardiomyopathies , Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Myocardial Perfusion Imaging , Humans , Female , Coronary Circulation/physiology , Myocardial Perfusion Imaging/methods , COVID-19/complications , COVID-19/diagnosis , Ammonia/pharmacology , SARS-CoV-2 , Tomography, X-Ray Computed , Positron-Emission Tomography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology
13.
Mymensingh Med J ; 31(4): 1108-1114, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2045555

ABSTRACT

It was previously reported that coronavirus caused myocardial injury in hospitalized patients. However, delayed cardiac involvement in symptomatic patient recovery from COVID-19 is not yet well known. The objective of this study was to evaluate cardiac involvement by using cardiac magnetic resonance (CMR) in symptomatic post-COVID-19 recovered patients. Thirty (30) patients who recovered from COVID-19 and had recently reported cardiac symptoms were studied in a prospective observational study performed at Popular Medical College Hospital, Dhaka, Bangladesh from March 2021 to September 2021. They underwent CMR examinations. CMR scanning protocol included the following: black blood, cine sequence, both short-axis and long-axis, T2-weight short tau inversion recovery (STIR) sequence, T2- weighted imaging (T2WI) and late gadolinium enhancement (LGE) and quantitative mapping sequences-native T1/T2 mapping and post-contrast T1 mapping. Myocardial edema and late gadolinium enhancement were assessed in all patients. Quantitative evaluation of native T1/T2 and ECV value and cardiac function were evaluated. There were 30 people in all in this study. The average age of the participants in the study was 36.6 years. Fourteen (46.6%) of the patients had abnormal cardiac MRI results, while the remaining 15(53.3%) had negative CMR findings. Among positive findings patients, 8(57.1%) of 14 had increased T2 signal. Increased myocardial edema was found in the same no of patients, involving 53.2% (128 of 224) of LV segments. Only 2 cases (2 of 14) showed mid myocardial and subepicardial LGE, involving 18 of 224, 8.03% of myocardial segments. Global native T1, T2 and ECV values are significantly elevated in all CMR positive findings patients. Native T1 1231ms (IQR: 1281.25-1257.5 versus 1155.5 (IQR: 1137.25-1172.75), T2 40 (IQR: 34.5-43.25) versus 35.5 (IQR: 34-37), ECV 31 (29.75-33.25) versus 23.5 (21.25-24.0), p<0.001; p<0.011 and p<0.001 respectively. Reduced RV functional were found in positive as compared with negative CMR findings patients, EF, 32.05 (IQR: 25.25-39.0) versus 54.5 (IQR: 52.0-57.75) and EDV, 117.5 (IQR: 102.0-134.25) versus 95.0 (IQR: 71.75-99.75), p<0.001 and p<0.001 respectively. In this study cardiac involvement was found in the post-COVID-19 recovered patient with cardiac symptoms. Cardiac MRI findings included myocardial edema, fibrosis and reduced right ventricular function. So attention should be paid to symptomatic post-COVID-19 recovered patients.


Subject(s)
COVID-19 , Cardiomyopathies , Adult , Bangladesh/epidemiology , COVID-19/complications , Cardiomyopathies/pathology , Contrast Media , Gadolinium , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging, Cine/adverse effects , Predictive Value of Tests , Tertiary Care Centers
14.
J Mol Cell Cardiol ; 172: 100-108, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2004619

ABSTRACT

Cardiovascular disease continues to be the leading health burden worldwide and with the rising rates in obesity and type II diabetes and ongoing effects of long COVID, it is anticipated that the burden of cardiovascular morbidity and mortality will increase. Calcium is essential to cardiac excitation and contraction. The main route for Ca2+ influx is the L-type Ca2+ channel (Cav1.2) and embryos that are homozygous null for the Cav1.2 gene are lethal at day 14 postcoitum. Acute changes in Ca2+ influx through the channel contribute to arrhythmia and sudden death, and chronic increases in intracellular Ca2+ contribute to pathological hypertrophy and heart failure. We use a multidisciplinary approach to study the regulation of the channel from the molecular level through to in vivo CRISPR mutant animal models. Here we describe some examples of our work from over 2 decades studying the role of the channel under physiological and pathological conditions. Our single channel analysis of purified human Cav1.2 protein in proteoliposomes has contributed to understanding direct molecular regulation of the channel including identifying the critical serine involved in the "fight or flight" response. Using the same approach we identified the cysteine responsible for altered function during oxidative stress. Chronic activation of the L-type Ca2+ channel during oxidative stress occurs as a result of persistent glutathionylation of the channel that contributes to the development of hypertrophy. We describe for the first time that activation of the channel alters mitochondrial function (and energetics) on a beat-to-beat basis via movement of cytoskeletal proteins. In translational studies we have used this response to "report" mitochondrial function in models of cardiomyopathy and to test efficacy of novel therapies to prevent cardiomyopathy.


Subject(s)
Calcium Channels, L-Type , Cardiomyopathies , Animals , Humans , Calcium/metabolism , Calcium Channels, L-Type/physiology , Cardiomyopathies/metabolism , COVID-19 , Diabetes Mellitus, Type 2/metabolism , Hypertrophy/metabolism , Myocytes, Cardiac/metabolism , Post-Acute COVID-19 Syndrome
15.
J Cardiovasc Magn Reson ; 24(1): 33, 2022 06 06.
Article in English | MEDLINE | ID: covidwho-1881271

ABSTRACT

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.


Subject(s)
Cardiomyopathies , Myocarditis , Cardiomyopathies/pathology , Contrast Media , Edema , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging, Cine/methods , Myocarditis/pathology , Myocardium/pathology , Predictive Value of Tests , Water
16.
Eur Heart J Cardiovasc Imaging ; 23(4): 450-464, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1886392

ABSTRACT

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Dilated , Myocarditis , Cardiomyopathies/pathology , Cytidine Monophosphate , Heart , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Myocarditis/diagnostic imaging , Myocardium/pathology
17.
Curr Cardiol Rep ; 24(6): 631-644, 2022 06.
Article in English | MEDLINE | ID: covidwho-1877492

ABSTRACT

PURPOSE OF REVIEW: The advent of induced pluripotent stem cells (iPSC) has paved the way for new in vitro models of human cardiomyopathy. Herein, we will review existing models of disease as well as strengths and limitations of the system. RECENT FINDINGS: Preclinical studies have now demonstrated that iPSCs generated from patients with both acquired or heritable genetic diseases retain properties of the disease in vitro and can be used as a model to study novel therapeutics. iPSCs can be differentiated in vitro into the cardiomyocyte lineage into cells resembling adult ventricular myocytes that retain properties of cardiovascular disease from their respective donor. iPSC pluripotency allows for them to be frozen, stored, and continually used to generate iPSC-derived myocytes for future experiments without need for invasive procedures or repeat myocyte isolations to obtain animal or human cardiac tissues. While not without their limitations, iPSC models offer new ways for studying patient-specific cardiomyopathies. iPSCs offer a high-throughput avenue for drug development, modeling of disease pathophysiology in vitro, and enabling experimental repair strategies without need for invasive procedures to obtain cardiac tissues.


Subject(s)
Cardiomyopathies , Cardiovascular Diseases , Induced Pluripotent Stem Cells , Animals , Cardiomyopathies/genetics , Cardiovascular Diseases/therapy , Cell Differentiation , Humans , Myocytes, Cardiac
18.
J Cardiovasc Med (Hagerstown) ; 23(5): 290-303, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1883852

ABSTRACT

In the past 20 years, cardiac computed tomography (CCT) has become a pivotal technique for the noninvasive diagnostic workup of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Randomized clinical trials documented the value of CCT in increasing the cost-effectiveness of the management of patients with acute chest pain presenting in the emergency department, also during the pandemic. Beyond the evaluation of stents and surgical graft patency, the anatomical and functional coronary imaging have the potential to guide treatment decision-making and planning for complex left main and three-vessel coronary disease. Furthermore, there has been an increasing demand to use CCT for preinterventional planning in minimally invasive procedures, such as transcatheter valve implantation and mitral valve repair. Yet, the use of CCT as a roadmap for tailored electrophysiological procedures has gained increasing importance to assure maximum success. In the meantime, innovations and advanced postprocessing tools have generated new potential applications of CCT from the simple coronary anatomy to the complete assessment of structural, functional and pathophysiological biomarkers of cardiac disease. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), represents the second of two consensus documents collecting the expert opinion of cardiologists and radiologists about current appropriate use of CCT.


Subject(s)
Cardiology , Cardiomyopathies , Heart Diseases , Neoplasms , Chest Pain , Coronary Artery Bypass , Humans , Radiology, Interventional , Stents , Tomography, X-Ray Computed/methods
19.
PLoS One ; 17(6): e0269247, 2022.
Article in English | MEDLINE | ID: covidwho-1879319

ABSTRACT

INTRODUCTION: Severe COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis-COVID-19 and influenza-in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases. METHODS AND ANALYSIS: In this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls. ETHICS AND DISSEMINATION: Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION: DRKS00024162.


Subject(s)
COVID-19 , Cardiomyopathies , Influenza, Human , Pulmonary Embolism , Sepsis , COVID-19/complications , Cohort Studies , Humans , Morbidity , Multicenter Studies as Topic , Prognosis , Prospective Studies , Sepsis/complications
20.
J Ayub Med Coll Abbottabad ; 34(2): 369-374, 2022.
Article in English | MEDLINE | ID: covidwho-1848218

ABSTRACT

The COVID-19 infection has spread rampantly, attaining pandemic status within three months of its first appearance. It has been classically associated with respiratory signs and symptoms. However, unusual presentations have also been reported in multiple literatures. We are reporting a case of acute heart failure in a pregnant patient diagnosed with Covid-19 infection. Her hospital course has been complicated by pneumonia and venous thrombosis during the postpartum period. Her laboratory investigations showed evidence of myocardial injury, acute heart failure, and COVID-19 infection in second PCR sample taken during postpartum period. Echocardiography exhibited features of severe left ventricle systolic dysfunction. She had successful delivery through caesarean-section, nevertheless, her postpartum period was complicated by pneumonia and right femoral venous thrombosis. CT scan of the chest and pulmonary arteries revealed infiltrations in the left lower lobe and right middle lobe, suggestive of consolidation, with no evidence of pulmonary embolism. Cardiac MRI displayed severe global LV and RV systolic dysfunction, but no evidence of myocardial infarction, myocardial infiltration, or abnormal myocardial delayed enhancement. Her condition improved and she was discharged on heart failure medications. During follow-up at the heart failure clinic, her symptoms continued to ameliorate, except the LV and RV systolic dysfunction which persisted. Multiple unusual presentations of Covid-19 infection have been reported in various literatures and screening of the COVID-19 infection should be practiced on regular basis especially among high-risk patients. Prompt identification of COVID-19 infection will lead to proper isolation and mitigation of infection spread among hospitalized patients and health care workers. Covid-19 PCR should be repeated in cases having clinical indication and negative first sample. A proper history and cardiac MRI can differentiate between different aetiologies of heart failure during pregnancy and peripartum COVID-19 infection. Adequate anticoagulation should be considered in COVID-19 patients due to the high risk of thromboembolism. Among patients with COVID-19 infection, CT chest helps demonstrate the extent of pulmonary involvement.


Subject(s)
COVID-19 , Cardiomyopathies , Heart Failure , Venous Thrombosis , COVID-19/complications , Cardiomyopathies/complications , Echocardiography/adverse effects , Female , Heart Failure/etiology , Humans , Pandemics , Pregnancy
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