Incidence, Clinical Presentation, and Management of Myocarditis following mRNA-Based Covid-19 Vaccines: A Brief Report.

BACKGROUND: Recent surveillance studies following nationwide mass vaccination are investigating rare complications such as myocarditis, pericarditis, and thromboembolic events related to mRNA-based Covid-19 vaccines. SUMMARY: In the current report, we present an overview of the incidence, clinical presentation and management of post-mRNA vaccine myocarditis, and pericarditis in view of the currently available data. Our main focus is directed toward myocarditis. KEY MESSAGES: Myocarditis following mRNA-based Covid-19 vaccines is rare, more frequently affects younger men <30 years and is usually of mild severity with spontaneous recovery. The overall benefit of mRNA vaccines in terms of protecting from severe Covid-19 infection and associated cardiovascular complications outweighs the risk of postvaccination myocarditis. Currently, there are no dedicated guidelines for patients with postvaccination myocarditis or pericarditis in terms of the frequency of follow-up including clinical assessment, repeated echocardiography, and cardiac resonance imaging. However, follow-up studies in terms of long-term consequences are underway.

Right ventricular postsystolic shortening: Resolution after opening a totally occluded right coronary artery.

Acute myocardial ischemia induces reduced systolic shortening and causes postsystolic shortening (PSS). Right ventricular (RV) PSS in coronary artery disease has been less studied. We present here the case of a 51-year-old woman admitted with a non-ST segment elevation myocardial infarction and significant PSS in the RV free-wall segments on two-dimensional speckle tracking echocardiography, suggesting ongoing ischemia. A cardiac CT demonstrated occluded proximal right coronary artery with a low-attenuated/soft plaque, confirmed by coronary angiography which was treated by percutaneous coronary intervention. At 3-week follow-up, there was complete resolution of the RV-PSS, with a more synchronized pattern of maximum myocardial shortening at systole.

The Norwegian Stroke in the Young Study (NOR-SYS): rationale and design.

BACKGROUND: Ischemic stroke in young adults is a major health problem being associated with a higher vascular morbidity and mortality compared to controls, and a stroke recurrence rate of 25% during the first decade. The assumed cause of infarction and the detected risk factors determine the early- and long-term treatment. However, for many patients the cause of stroke remains unknown. Risk factor profile and etiology differ in young and elderly ischemic stroke patients, and atherosclerosis is the determined underlying condition in 10 to 15%. However, subclinical atherosclerosis is probably more prevalent and may go unrecognized. METHODS/DESIGN: NOR-SYS is a prospective long-term research program. Standardized methods are used for anamnestic, clinical, laboratory, imaging, and ultrasound data collection in ischemic stroke patients aged ≤60 years, their partners and joint adult offspring. The ultrasound protocol includes the assessment of intracranial, carotid and femoral arteries, abdominal aorta, and the estimation of VAT. To date, the study is a single centre study with approximately 400 patients, 250 partners and 350 adult offspring expected to be recruited at our site. DISCUSSION: NOR-SYS aims to increase our knowledge about heredity and the development of arterial vascular disease in young patients with ischemic stroke and their families. Moreover, optimization of diagnostics, prophylaxis and early intervention are major targets with the intention to reduce stroke recurrence and other clinical arterial events, physical disability, cognitive impairment and death.

Assessment of vascular reactivity in the peripheral and coronary arteries by Cine 3T-magnetic resonance imaging in young normotensive adults after surgery for coarctation of the aorta.

This study aimed to investigate whether coarctation of the aorta in infancy indicates an altered vascular reactivity in the peripheral and coronary arteries apart from the secondary effect of hypertension or other complications of the disease. Patients with repaired coarctation of the aorta have a high prevalence of premature cardiovascular complications. The etiology still is not fully understood, and the cause is most likely multifactorial. Endothelial function was assessed by peripheral flow mediated dilation (FMD) and coronary flow reserve (CFR) in a study of 10 control subjects and 10 patients with a successfully repaired coarctation of the aorta (mean age, 20.9 years; 20.5 years after repair). No one had re- or rest-coarctation of the aorta, hypertension, pathologic blood pressure response during exercise, or associated cardiac malformations such as bicuspid aortic valve. CFR was achieved by phase-contrast velocity encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min). FMD was measured in the brachial artery before and after 5 min of arterial occlusion. A normal CFR and FMD was found in both groups. Most studies have been conducted with large, unselected groups. The current study group represented the best outcome of the coarctation spectrum (i.e., patients with no evidence of a residual gradient across the coarctation site or systemic hypertension). The findings reassuringly suggest that significant endothelial dysfunction and atherosclerotic changes were not present in this selected cohort.

A short-time model to study relevant indices of cardiotoxicity of doxorubicin in the rat.

AIM: Short-time models (STM) to study the cardiotoxicity (acute or chronic) of doxorubicin in rats are of interest to assess protective interventions and pathways. STM promotes more ethical animal treatment with less stress, and at a lower cost compared to established long-time models (LTM). We wanted to investigate if an STM of 9 d yields the same information regarding cardiotoxicity as an LTM of 9 weeks. METHODS: Male Wistar rats received identical drug administration protocols in STM and LTM. The two intervention groups (n = 6) received intraperitoneal (i.p.) injections of 2 mg/kg doxorubicin every day for five consecutive days, with a total cumulative dose of 10 mg/kg. The two control groups (n = 6), received an equivalent volume of saline injected every day for five consecutive days. Hearts from STM and LTM were excised and Langendorff-perfused after 9 d or 9 weeks, respectively, after the first drug injection. Cardiotoxicity was assessed in paced Langendorff hearts by a release of hydrogenperoxide (H2O2) and troponin T (TnT) in effluent, by myocardial accumulation of doxorubicin and its metabolite doxorubicinol, and by physiological parameters recorded during pressure, or volume-regulated perfusion. RESULTS: In STM, hearts exposed to doxorubicin demonstrated a 15% reduction in left ventricular developed pressure (LVDP) irrespective of flow mode, and a 13% increase in aortic pressure (AoP), during volume-regulated perfusion, an index of coronary resistance, compared to controls. Left ventricular end-diastolic pressure (LVEDP) was increased by 72% during pressure-regulated perfusion and 100% during volume-regulated perfusion in STM. In LTM, hearts exposed to doxorubicin demonstrated a 40% reduction in LVDP during pressure-regulated perfusion and a 20% reduction during volume-regulated perfusion. LVEDP was 70% higher in doxorubicin-treated hearts during pressure-regulated perfusion and 80% higher during volume-regulated perfusion. In addition, aortic pressure was increased by 30% during volume-regulated perfusion. In both STM and LTM, hearts exposed to doxorubicin demonstrated a higher H2O2 and TnT release, compared to respective controls. The difference was most pronounced in STM. Myocardial content of doxorubicin was detectable in both STM and LTM. However, doxorubicinol was only detectable in STM. CONCLUSION: STM is comparable to LTM to study relevant indices of cardiotoxicity of doxorubicin in rat hearts. Biochemical differences are more pronounced in STM, while contractile differences are more pronounced in LTM. STM could be a preferred model for preliminary studies of protective interventions.

Long-term multimodality imaging follow-up of ST-segment elevation myocardial infarction patients treated with bioresorbable vascular scaffold: advantages and challenges.

BACKGROUND: Multislice computed tomography (MSCT) offers a non-invasive method of imaging bioresorbable scaffolds (BRS). OBJECTIVES: To investigate the advantages and challenges using MSCT in the follow-up after BRS implantation. METHOD: The BRS cohort consisting of 31 patients in the 'BRS in STEMI' trial was examined by multimodality imaging and followed long-term. Minimum lumen area (MLA) and average lumen area (ALA) were examined 12 and 36 months after BRS implantation with MSCT. Optical coherence tomography (OCT) at 12 months was used as a reference. RESULTS: Measured by MSCT, the mean MLA was 0.05 ±â€…1.32 mm² ( P  = 0.85), but ALA was 1.32 (±2.59 mm², P  = 0.015) greater than by OCT. ALA and MLA did not change significantly from 12 to 36 months. MSCT identified all cases of restenosis but missed one patient with massive malapposition. CONCLUSION: Our data support using MSCT in the follow-up after BRS implantation. Invasive investigation should still be considered for patients with unexplained symptoms.

Epicardial adipose tissue volume, plaque vulnerability and myocardial ischemia in non-obstructive coronary artery disease.

Background: Epicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Whether increased EAT volume is associated with coronary plaque vulnerability and demand myocardial ischemia in patients with non-obstructive coronary artery disease (CAD) is less explored. Methods: In 125 patients (median age 63[58, 69] years and 58% women) with chest pain and non-obstructive CAD, EAT volume was quantified on non-contrast cardiac CT images. EAT volume in the highest tertile (>125 ml) was defined as high EAT volume. Total coronary plaque volume and plaque vulnerability were quantified by coronary CT angiography (CCTA). Demand myocardial ischemia was detected by contrast dobutamine stress echocardiography. Results: High EAT volume was more common in men and associated with higher BMI, hypertension, increased left ventricular mass index (LVMi), C-reactive protein (CRP) and positive remodelling (all p < 0.05). There was no difference in age, coronary calcium score, total and non-calcified plaque volume or presence of demand myocardial ischemia between groups (all p ≥ 0.34). In a multivariable model, obesity (p = 0.006), hypertension (p = 0.007) and LVMi (p = 0.016) were independently associated with high EAT volume. Including plaque vulnerability in an alternative model, positive remodelling (p = 0.038) was independently associated with high EAT volume. Conclusion: In non-obstructive CAD, high EAT volume was associated with cardiometabolic risk factors, inflammation and plaque vulnerability, while there was no association with demand myocardial ischemia or coronary plaque volume. Following our results, the role of EAT volume as a biomarker in non-obstructive CAD remains unclear.

Cardiac Involvement in Systemic and Local Vasculitides: The Value of Noninvasive Multimodality Imaging.

Despite significant advances in managing systemic vasculitides, cardiovascular morbidity, and mortality are still of primary concern. Advances in noninvasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance , positron emission tomography, and computed tomography angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multimodality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and cardiac magnetic resonance to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between cardiologists and rheumatologists.

Effects of local delivery of tetradecylthioacetic acid within the injured coronary vessel wall.

OBJECTIVES: Inflammation is involved in cell proliferation and collagen deposition causing vessel wall remodeling and restenosis after plain balloon angioplasty. Local drug delivery of bioactive agents that reduce the incidence of adverse wall remodeling is of considerable interest concerning treatment strategies for coronary vessel disease and could alter the need of repeated revascularization. DESIGN: In this study, 34 domestic pigs undergoing coronary balloon injury were randomly assigned to Tetradecylthioacetic acid (TTA) or placebo delivered locally. After four weeks, vessel wall collagen density, inflammatory markers and lipid fractions were assessed as well as cell proliferation. RESULTS: Collagen particle count was lower after TTA compared to placebo, 177 ± 11 n/area versus 225 ± 13 n/area (p = 0.007). Interleukin-2 (IL-2) concentration was reduced, 1.6 ± 0.02 pg/ml versus 2.6 ± 0.5 pg/ml, (p = 0.01). The anti-inflammatory index was increased after TTA, 46.28 ± 12.1 versus 34.66 ± 4.5, (p = 0.025). There were no differences between TTA and placebo with regard to cell proliferation. CONCLUSIONS: Local delivery of TTA reduced the local inflammatory response and collagen accumulation. Local balloon delivery of TTA into the vessel wall may represent an alternative antiproliferative strategy for preventing restenosis, in particular for vessels with obstructive disease not available for stent implantation.

Assessment of coronary flow reserve in the coronary sinus by cine 3T-magnetic resonance imaging in young adults after surgery for tetralogy of Fallot.

This study aimed to evaluate CFR by assessing blood flow in the coronary sinus and systemic endothelial function measured by FMD of the brachial artery in an open prospective study of 10 control subjects and 10 patients (ages, 15-25 years) who have undergone surgical TOF repair. Reduced ventricular function, impaired exercise capacity, and ventricular arrhythmia have been proposed as risk factors for sudden cardiac death after surgical repair of TOF. Some of this may be related to impaired myocardial perfusion. A 3.0T GE Signa Excite scanner was used to achieve phase-contrast, velocity-encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min). FMD was measured in the brachial artery before arterial occlusion and 5 min afterward. The TOF group demonstrated significantly higher volumetric blood flow in the coronary sinus (282 ± 63 ml/min) than the normal control subjects at rest (184 ± 57 ml/min) (P = 0.006). During adenosine infusion, this difference disappeared. The CFR was 2.00 ± 0.43 in the control group and 1.19 ± 0.34 in the TOF group (P = 0.002). No correlation between FMD and CFR was observed in the study group (r (s) = 0.61, n = 8, P = 0.15). This study showed a reduced CFR due to a higher blood flow of the subject at rest in the TOF group. This reduced CFR may disable a normal adaptation to increased oxygen demand during exercise and increase myocardial vulnerability to reduced blood supply postoperatively for TOF patients with coronary heart disease.

Effect of radiographer-led intervention on reassurance, treatment satisfaction, and recurring chest pain in patients with a normal coronary computed tomography angiography-a randomized controlled trial.

BACKGROUND: Chest pain is a common complaint in the general practitioner's (GP) office. Computed tomography (CT) is one of the main diagnostic tools available for assessing coronary artery disease (CAD), with a low probability of a false-negative result (<1%). Despite normal CT findings, many patients with non-coronary chest pain believe they suffer from CAD. AIMS: To determine the effect of an intervention on reassurance, treatment satisfaction, and recurring chest pain in patients with non-coronary chest pain at follow-up after 1 month. METHODS: Patients with chest pain, but with normal coronary CT angiography, i.e., no CAD, were randomized into two groups. The intervention group received extended information about the CT examination, including visualization of their individual coronary calcium score images, before the radiographer conveyed the final examination result. The control group received standard care, i.e., neither extended information nor the examination result and were encouraged to consult their referring cardiologist or GP after 1 week. Items from the Seattle Angina Questionnaire and a question regarding reassurance measured the effect of the intervention at follow-up after 1 month. RESULTS: The study included 92 patients, 63 female and 29 male, with a follow-up response rate of 80%. Reassurance and overall treatment satisfaction were significantly higher in the intervention group (P = 0.016 and P = 0.046 respectively). The incidence of chest pain was significantly reduced in the intervention group (P = 0.042). CONCLUSION: This study demonstrated that the intervention group showed significantly higher reassurance, overall treatment satisfaction, and experienced significantly less chest pain at follow-up after 1 month. CLINICAL TRIALS DATABASE ID: NCT03781661.

Relationship between hypertension and non-obstructive coronary artery disease in chronic coronary syndrome (the NORIC registry).

BACKGROUND: The burden of non-obstructive coronary artery disease (CAD) in the society is high, and there is currently limited evidence-based recommendation for risk stratification and treatment. Previous studies have demonstrated an association between increasing extent of non-obstructive CAD and cardiovascular events. Whether hypertension, a modifiable cardiovascular risk factor, is associated with extensive non-obstructive CAD in patients with symptomatic chronic coronary syndrome (CCS) remains unclear. METHODS: We included 1138 patients (mean age 62±11 years, 48% women) with symptomatic CCS and non-obstructive CAD (1-49% lumen diameter reduction) by coronary computed tomography angiography (CCTA) from the Norwegian Registry for Invasive Cardiology (NORIC). The extent of non-obstructive CAD was assessed as coronary artery segment involvement score (SIS), and extensive non-obstructive CAD was adjudicated when SIS >4. Hypertension was defined as known hypertension or use of antihypertensive medication. RESULTS: Hypertension was found in 45% of patients. Hypertensive patients were older, with a higher SIS, calcium score, and prevalence of comorbidities and statin therapy compared to the normotensive (all p<0.05). There was no difference in the prevalence of hypertension between sexes. Univariable analysis revealed a significant association between hypertension and non-obstructive CAD. In multivariable analysis, hypertension remained associated with extensive non-obstructive CAD, independent of sex, age, smoking, diabetes, statin treatment, obesity and calcium score (OR 1.85, 95% CI [1.22-2.80], p = 0.004). CONCLUSION: In symptomatic CCS, hypertension was associated with extensive non-obstructive CAD by CCTA. Whether hypertension may be a new treatment target in symptomatic non-obstructive CAD needs to be explored in future studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Identifier NCT04009421.

Factors associated with coronary heart disease in COPD patients and controls.

BACKGROUND: COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. METHODS: 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. RESULTS: 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p<0.01), whereas 55.9% of the COPD patients had a CaSc>100 compared to 31.6% of the controls (p<0.01). In a multivariable model adjusting for sex, age, body composition, pack-years, CRP, cholesterol/blood pressure lowering medication use and diabetes mellitus, the OR (95% CI) for having significant stenosis was 1.80 (0.86-3.78) in COPD patients compared with controls. In a similar model, the OR (95% CI) for having CaSc>100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. CONCLUSION: COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.

The value of multimodality imaging in hypertensive heart disease.

Hypertensive heart disease (HHD) includes left ventricular (LV) functional and structural remodeling. For a long time, this involved only LV diastolic dysfunction and LV hypertrophy. However, development of imaging technique enabled more detailed insights into LV mechanics. Its impairment seems to be the first step in the cascade of HHD. Tissue characterization, obtained by cardiac magnetic resonance, opened a completely new chapter in the assessment of HHD. We report a case of a 47-year-old man who was referred to our department for a newly detected heart failure. CT angiography excluded relevant coronary disease and cardiac magnetic resonance revealed focuses of fibrosis in interventricular septum, in addition severely dilated LV with severely reduced ejection fraction. Considering the fact that the patient had longstanding uncontrolled arterial hypertension and that other causes of cardiac remodeling and dysfunction were excluded, we hypothesized that the multimodality imaging approach enabled prompt diagnosis of HHD.

Coronavirus disease 2019 and cardiovascular complications: focused clinical review.

The coronavirus disease 2019 (COVID-19) may cause not only an acute respiratory distress syndrome (ARDS) but also multiple organ damage and failure requiring intensive care and leading to death. Male sex, advanced age, chronic lung disease, chronic kidney disease and cardiovascular disease, such as hypertension, diabetes and obesity have been identified as risk factors for the COVID-19 severity. Presumably, as these three cardiovascular risk factors are associated with a high prevalence of multiorgan damage. In the present focused clinical review, we will discuss the cardiovascular complications of COVID-19 including acute cardiovascular syndrome (acute cardiac injury/COVID cardiomyopathy, thromboembolic complications and arrhythmias) and post-COVID-19 sequelae. Preliminary data shows that the cause of acute cardiovascular syndrome may be multifactorial and involve direct viral invasion of the heart and vascular system, as well as through the immune and inflammation-mediated systemic cytokine storm. COVID-19 survivors may also show persistently elevated blood pressure and sinus tachycardia at rest. Furthermore, poor diabetic control, persistent renal damage and cerebral sequelae, such as persistent cognitive and neuropsychiatric alterations are also frequently reported. A particular attention should be paid towards cardiovascular protection in COVID-19 patients who develop acute cardiovascular syndromes during hospitalization, and/or permanent/semipermanent sequelae after recovery from COVID-19. These conditions may require careful clinical assessment, treatment and close follow-up to avoid short-term and long-term complications.

Acute Myocardial Injury in a Patient with Attention Deficit Hyperactivity Disorder and History of Substance Abuse: A Multimodality Imaging Point of View.

Both cannabis and amphetamine are the most commonly used illegal substances worldwide and are associated with a number of adverse cardiovascular effects including transient coronary vasospasm. Here, we present the case of a 39-year-old male admitted to our institution with a 6-h history of severe chest pain and ST-segment elevation on the ECG. Coronary angiography on admission showed normal coronary arteries. The patient had a 14-year history of substance abuse, primarily amphetamine and cannabis, and was prescribed lisdexamfetamin (Aduvanz®) for attention deficit hyperactivity disorder (ADHD) for the past 2 years. A cardiac magnetic resonance (CMR) the following day showed widely distributed focal lesions of late gadolinium enhancement in mid- and sub-epicardial myocardium in the anterior, lateral and inferior walls, suggestive of chronic fibrotic lesions. There was no sign of acute myocardial edema. No viral cause was identified during a thorough investigation, including negative SARS-COV-2 and endomyocardial biopsy. Substance-abuse-induced coronary vasospasm leading to ST-segment elevation, myocardial damage with a rise and fall of cardiac TnT, as well as a slightly reduced left ventricular ejection fraction (48%) and regional wall motion abnormalities on echocardiography, was the most likely diagnosis.