Role of Cardiac Magnetic Resonance Imaging in the Evaluation of Athletes with Premature Ventricular Beats

Premature ventricular beats (PVBs) in athletes are not rare. The risk of PVBs depends on the presence of an underlying pathological myocardial substrate predisposing the subject to sudden cardiac death. The standard diagnostic work-up of athletes with PVBs includes an examination of family and personal history, resting electrocardiogram (ECG), 24 h ambulatory ECG (possibly with a 12-lead configuration and including a training session), maximal exercise testing and echocardiography. Despite its fundamental role in the diagnostic assessment of athletes with PVBs, echocardiography has very limited sensitivity in detecting the presence of non-ischemic left ventricular scars, which can be revealed only through more in-depth studies, particularly with the use of contrast-enhanced cardiac magnetic resonance (CMR) imaging. The morphology, complexity and exercise inducibility of PVBs can help estimate the probability of an underlying heart disease. Based on these features, CMR imaging may be indicated even when echocardiography is normal. This review focuses on interpreting PVBs, and on the indication and role of CMR imaging in the diagnostic evaluation of athletes, with a special focus on non-ischemic left ventricular scars that are an emerging substrate of cardiac arrest during sport.

Effect of Shenfu Injection on Reperfusion Injury in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Segment Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial

Background: Shenfu injection is a traditional Chinese medicine formulation that alleviates ischemia-reperfusion injury through multiple pharmacologic effects. However, no data are available regarding its efficacy in patients with myocardial infarction. We aimed to examine the effects of Shenfu injection on infarct size in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: From April 2016 to February 2018, 40 patients with first-time anterior STEMI undergoing primary PCI within 6 h of symptom onset were randomized 1:1 to intravenous Shenfu injection (80 ml Shenfu injection + 70 ml 5% glucose injection) or placebo (150 ml 5% glucose injection) before reperfusion. Treatment started before PCI and maintained for 5 days after PCI. The primary end point was infarct size assessed by CK-MB area under the curve (AUC) over 72 h and cardiac magnetic resonance (CMR) imaging 4 ± 1 days after PCI.Results: Infarct size by area under the curve for CK-MB over 72 h did not differ between the Shenfu injection and placebo groups (5602.5 [3539.4–7526.4] vs. 6403.2 [2234.4–8340.6] ng·h/ml, P = 0.82). Among 32 patients who underwent CMR Imaging, a nominal reduction in infarct size was observed in the Shenfu injection group compared with the placebo group (23.9 [15.2–28.5] % vs. 27 [21.9–31.9] %, P = 0.42). After excluding patients with no or minimal infarct, there was a trend toward reduction in infarct size in the Shenfu injection group (24.1 [20.3–29.3] % vs. 29.1 [24.5–32] %, P = 0.18). Incidence of adverse events was similar between the groups.Conclusions: This pilot study showed that the use of Shenfu injection was safe but did not reduce infarct size by CMR Imaging and CK-MB release kinetics in reperfused patients with STEMI. Larger studies (confining to patients with extensive infarct size) to evaluate the efficacy of Shenfu injection on reperfusion injury are warranted.Clinical Trail Registration:clinicaltrials.gov, identifier: NCT02709798.

196 Cardiovascular magnetic resonance characterization of myocardial injury in recovered COVID-19 patients with elevated troponins during hospital stay

Aims Despite being a common finding in hospitalized COVID-19 patients, cardiac troponin elevation remains a nonspecific detection of myocardial injury and further in-hospital investigation into the cause of myocardial injury is rarely done. COVID-19 patients with myocardial injury show a significantly higher in-hospital mortality rate compared with those without myocardial injury and among those with myocardial injury, greater degrees of troponin elevation are associated with higher mortality rates. There are still many questions regarding possible cardiovascular sequelae and prognostic significance in these patients. Being able to distinguish between inflammatory and ischaemic causes of myocardial injury cardiovascular magnetic resonance (CMR) is the non-invasive modality of choice to investigate myocardial involvement in these patients. Presented are the preliminary single-centre results from a multicentre study aimed to characterize the prevalence, type and extent of COVID-19-related cardiovascular sequelae using CMR imaging. Methods and results In this single-centre prospective observational cohort study, patients hospitalized with confirmed COVID-19 and at least one value of high sensitivity I troponin (hs-Tnl) >99th percentile during hospitalization were eligible for follow-up contrast-enhanced CMR imaging. Patients with any standard CMR contraindications were excluded. Images were acquired using a standardized myocarditis protocol including late gadolinium enhancement (LGE) and T1 and T2 mapping. Cutoff values of 1015 ms and 50 ms were used for abnormal T1 and T2 measurements, respectively. Of the 21 patients (65 ± 11.85 years) who underwent imaging, 15 (71.4%) were male. The mean follow-up duration from the date of confirmed COVID-19 diagnosis was 169 ± 19 days. The mean left ventricular ejection fraction was 64.1 ± 13.87 and 3 (14.3%) patients had evidence of wall motion abnormalities. LGE was seen in 9/20 (45.0%) patients, reflecting myocardial fibrosis. Increased native T1 signal representing myocardial fibrosis and/or oedema was seen in 9/20 (45.0%) patients. While increased native T2 signal, being more specific for oedema was observed in 3/20 (15.0%) patients. Considering CMR findings, 6 (28.6%) patients showed evidence of previous myocarditis. Conclusions In this single centre Italian study of patients hospitalized with COVID-19 and elevated cardiac enzymes, myocarditis-like injury was evident in about a quarter of the patients. Whether these findings will lead to long-term cardiac complications is still to be confirmed.

Longitudinal Changes of Cardiac and Aortic Imaging Phenotypes Following COVID-19 in the UK Biobank Cohort

Case studies conducted after recovery from acute infection with SARS-CoV-2 have frequently identified abnormalities on CMR imaging, suggesting the possibility that SARS-CoV-2 infection commonly leads to cardiac pathology. However, these observations have not been able to distinguish between associations that reflect pre-existing cardiac abnormalities (that might confer a greater likelihood of more severe infection) from those that arise as consequences of infection. To address this question, UK Biobank volunteers (n=1285; 54.5% women; mean age at baseline, 59.8 years old; 96.3% white) who attended an imaging assessment including cardiac magnetic resonance (CMR) before the start of the COVID-19 pandemic were invited to attend a second imaging assessment in 2021. Cases with evidence of previous SARS-CoV-2 infection were identified through linkage to PCR-testing or other medical records, or a positive antibody lateral flow test; n=640 in data available on 22 Sep 2021) and were matched to controls with no evidence of previous infection (n=645). The majority of these infections were milder and did not involve hospitalisation. Measures of cardiac and aortic structure and function were derived from the CMR images obtained on the cases before and after SARS-CoV-2 infection from images for the controls obtained over the same time interval using a previously validated, automated algorithm. Cases and controls had similar cardiac and aortic imaging phenotypes at their first imaging assessment. Changes between CMR imaging measures in cases before and after infection were not significantly different from those in the matched control group. Additional adjustment for comorbidities made no material difference to the results. While these results are preliminary and limited to imaging metrics derived from automated analyses, they do not suggest clinically significant persistent cardiac pathology in the UK Biobank population after generally milder (non-hospitalised) SARS-CoV-2 infection.

Patterns of cardiac involvement in patients with long COVID syndrome using cardiovascular magnetic resonance

Background Long COVID (LC) is an increasingly recognized late complication of COVID-19 infection. Cardiovascular involvement has also been implicated, however, the type and extent of the underlying cardiovascular injury remains unknown. Purpose To evaluate the association between ongoing symptoms and findings with cardiovascular magnetic resonance (CMR) in consecutive patients recently recovered from COVID-19 illness. Methods Prospective observational cohort study of patients recently recovered from COVID-19 illness and no previously known cardiovascular disease were included between April 2020 and April 2021. Demographic characteristics, cardiac blood markers, and CMR imaging a minimum of 4 weeks from the diagnosis were obtained. Results Of the 389 included patients, 192 (49%) were male, the mean (±standard deviation) age was 44 (±13) years and 61 (16%) required hospitalization during the acute illness. The median (IQR) time interval between COVID-19 diagnosis and CMR was 94 (71–165) days. 298 (77%) of patients continued to experience ongoing cardiovascular symptoms (long COVID, LC), including dyspnea, palpitations, atypical chest pain and fatigue at the time of CMR at least 4 weeks after the infection. In most patients, the symptoms were only effort related 137 (46%), whereas in 98 (33%) the symptoms affected the activities of daily life; 10 (3%) had severe and debilitating symptoms at rest. Compared to those with no LC (NLC, n=91), LC patients were more commonly hospitalized, had significantly higher native T1, native T2, and showed pericardial enhancement and effusion (Figure 1). There were no differences in cardiac biomarkers, left ventricular (LV) and right ventricular ejection fraction and mass. Proportionally, men and women were similarly affected (n=144 (73%) vs. n=157 (80%), p=0.18). Previous hospitalization was associated with hypertension and ongoing detectable troponin. LC status was associated with previous hospitalization and CMR findings of raised native T1 and native T2, and in females also pericardial enhancement. Severity of symptoms were associated with increased native T1 and T2 and decreased end-diastolic volume, whereas cardiac function showed no significant difference. Conclusions In this cohort of patients recently recovered from COVID-19 infection, ongoing cardiovascular symptoms were common. The LC status was related to previous hospitalization and CMR imaging findings of myopericardial inflammation. The extent and type of cardiovascular findings was associated with the severity of symptoms. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The German Heart Foundation (Deutsche Herzstiftung) and Bayer AG, Leverkusen, Germany Figure 1

68Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis

BackgroundImmune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography–CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited. Thus, we investigated the value of 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) PET/CT for the early detection and diagnosis of ICI-related myocarditis.MethodsConsecutive patients with clinically suspected ICI-related myocarditis from July 2018 to February 2021 were retrospectively evaluated in this single-center study. All patients underwent imaging for the detection of ICI-related myocarditis using either cardiac magnetic resonance (CMR) imaging or 68Ga-DOTATOC PET/CT. PET/CT images were acquired 90 min after the injection of 2 MBq/kg 68Ga-DOTATOC with pathological myocardial uptake in the left ventricle (LV) suggestive of myocarditis defined using a myocardium-to-background ratio of peak standard uptake value to mean intracavitary LV standard uptake (MBRpeak) value above 1.6. Patients had a full cardiological work-up including ECG, echocardiography, serum cardiac troponin I (cTnI), cardiac troponin T and creatine kinase (CK), CK-MB. Endomyocardial biopsy and inflammatory cytokine markers were also analyzed. The detection rate of ICI-related myocarditis using 68Ga-DOTATOC PET/CT and CMR was assessed.ResultsA total of 11 patients had clinically suspected ICI-related myocarditis; 9 underwent 68Ga -DOTATOC PET/CT. All nine (100%) patients with 68Ga-DOTATOC PET/CT presented with pathological myocardial uptake in the LV that was suggestive of myocarditis (MBRpeak of 3.2±0.8, range 2.2–4.4). Eight patients had CMR imaging and 3/8 (38%) patients had lesions evocative of myocarditis. All PET-positive patients were previously treated with a high dose of steroids and intravenous immunoglobulin prior to PET/CT had elevated serum cTnI except for one patient for whom PET/CT was delayed several days. Interestingly, in 5/6 (83%) patients who presented with concomitant myositis, pathological uptake was seen on whole-body 68Ga-DOTATOC PET/CT images in the skeletal muscles, suggesting an additional advantage of this method to assess the full extent of the disease. In contrast, four patients with CMR imaging had negative findings despite having elevated serum cTnI levels (range 20.5–5896.1 ng/mL), thus defining possible myocarditis. Newly identified immune correlates could provide specific biomarkers for the diagnosis of ICI-related myocarditis. Most tested patients (six of seven patients) had serum increases in the inflammatory cytokine interleukin (IL)-6 and in the chemokines CXCL9, CXCL10, and CXCL13, and the mass cytometry phenotypes of immune cell populations in the blood also showed correlations with myocardial inflammation. Four of five patients with myocarditis exhibited a Th1/Th2 imbalance favoring a pronounced inflammatory Th1, Th1/Th17, and Th17 CD4 memory T-cell response. The high proportion of non-classical monocytes and significantly reduced levels of CD31 in four to five patients was also consistent with an inflammatory disease.ConclusionThe use of 68Ga-DOTATOC PET/CT along with immune correlates is a highly sensitive method to detect ICI-related myocarditis especially in the early stage of myocardial inflammation, as patients with elevated cTnI may present normal CMR imaging results. 68Ga-DOTATOC PET/CT is also useful for detecting concomitant myositis. These results need to be confirmed in a larger population of patients and validated against a histological gold standard if available.

Preponderance of right ventricular dysfunction in COVID-19 patients with inflammatory heart disease

Introduction Recently published data suggests that inflammatory heart disease (IHD) is far more prevalent in COVID-19 patients than initially expected. Specifically, there have been reports of greater than expected right ventricular (RV) involvement in the post COVID-19 recovery period. However, there are no published data comparing RV dysfunction in COVID-19 and non-COVID-19 patient cohorts with IHD. Purpose This study was designed to assess and compare the prevalence of RV hypokinesis in 2 patient cohorts: patients with COVID-19 related IHD and patients with non-COVID-19 related IHD, based on cardiac MRI findings (CMR). Methods An institutional cardiac imaging database was queried for all patients with IHD documented by CMR. Inflammatory heart disease was defined as pericarditis and/or myocarditis using the recently modified Lake Louise criteria, including T1 and T2 relaxation mapping. The prevalence of IHD was evaluated in 2 separate patient cohorts, subjects with COVID-19 related IHD and subjects with non-COVID-19 related IHD. Further assessment of these 2 patients cohorts included the presence of RV hypokinesis. A two-tailed Z-test was used for statistical comparison of the presence of IHD and the presence of RV hypokinesis in these 2 patient cohorts. Results 62 COVID patients and 6782 non-COVID patients were identified in the imaging database. 53 of the 62 COVID patients (85.5%) had evidence of IHD on CMR study. In contrast, 1273 of the 6782 patients (18.8%) had documented IHD detected by CMR. There was a statistically significant difference between the incidence of IHD in the 2 patient groups (p-value <0.ehab724.01391). Furthermore, of the 53 COVID patients with IHD, 30 (56.6%) showed evidence of RV hypokinesis on CMR. Of the 1273 non-COVID patients with IHD, only 126 (9.9%) showed evidence of RV hypokinesis on CMR. There was a statistically significant difference between the incidence of RV hypokinesis among the 2 groups (p-value <0.ehab724.01391). Details are provided in Figure 1. Conclusion These data suggest that the prevalence of IHD in COVID-19 patients is 4 times greater than in patients with a non-COVID etiology, based on CMR imaging findings. Furthermore, the occurrence of RV hypokinesis is 5 times greater in COVID-19 patients than in IHD patients with a non-COVID etiology, also based on CMR findings. These data suggest that CMR imaging is of value in detecting both IHD and RV dysfunction, which are often difficult to detect with other imaging modalities. FUNDunding Acknowledgement Type of funding sources: None.