CMR feature tracking strain (CMR-FT) provides prognostic information. However, there is a paucity of data in hypertrophic cardiomyopathy (HCM). We sought to analyze global CMR-FT parameters in all four cardiac chambers and to assess associations with NT-proBNP and cardiac troponin T (hsTnT) in patients with HCM.LAX-GLS), circumferential (LVLAX-GCS) and radial strain (LVLAX-GRS) on long -axis (LAX) and as LVSAX-GCS and LVSAX-GRS on short- axis (SAX). Right ventricular (RV-GLS), left atrial (LA-GLS) and right atrial (RA-GLS) strain were assessed on LAX.This retrospective study included 144 HCM patients and 16 healthy controls with CMR at 1.5 T. Analyses were performed on standard steady-state free precession cine (SSFP) CMR data using a commercially available software. Global left ventricular (LV) strain was assessed as longitudinal , − 23.5  %, p = 0.0001), LVSAX-GRS  and LALAX-GLS  to be impaired in HCM compared to healthy controls despite normal LVEF. Furthermore, LV and LA strain parameters were impaired in HCM with elevated NT-proBNP and/or hsTnT, despite preserved LVEF compared to HCM with normal biomarker levels. There was a moderate correlation of LV and LA CMR-FT with levels of NT-proBNP and hsTnT.We found LVCMR-FT reveals LV and LA dysfunction in HCM despite normal LVEF. The association between impaired LV strain and elevated NT-proBNP and hsTnT indicates a link between unapparent functional abnormalities and disease severity in HCM.Typical CMR-FT findings in patients with hypertrophic cardiomyopathy LAXGLS), was associated with major cardiovascular events in HCM . Typical imaging parameters were: voxel size 1.36 × 1.36 × 6 mmCMR data analysis was performed by two trained observers who were blinded to all clinical information. Commercially available post-processing software  was used to assess volumes and function of all cardiac chambers. LV and RV volumes, as well as LV mass and LV maximal wall thickness, were obtained from cine SAX. LA and RA volumetry were obtained from cine LAX as recommended .CMR-FT measurements were performed using the QStrain application of Medis Suite MR . To genep < 0.05 without correction for multiple testing.Statistical analysis was performed using MedCalc for Windows, version 12.7.7.0 . Continuous data are presented as median and IQR. Categorical data are presented as numbers and percentage. Inter-observer agreement was assessed by intra-class correlation coefficients (ICC) and ICC values indicated poor (< 0.5), moderate (0.5–0.75), good (0.75–0.9) or excellent (> 0.9) reliability . ContinuLAX-GLS 0.95 , LVLAX-GCS 0.84 , LVLAX-GRS 0.40 , LVSAX-GRS 0.89 , LVSAX-GCS 0.66 , LA2CH-GLS 0.97 , LA4CH-GLS 0.97 , RV-GLS 0.94 , and RA-GLS 0.94 .Inter-observer agreement of CMR-FT strain parameters was as follows: ICC LVLAX-GLS of HCM patients was significantly lower compared to controls [− 18.9 , − 23.5  %, p = 0.0001; Table SAX-GRS, LA2CH-GLS and LA4CH-GLS were significantly lower in the HCM group compared to controls , maximal LV wall thickness (LVWT) and median LA volumes were significantly higher in HCM patients compared to controls Table . Eighty-LAX-GLS, LVLAX-GCS, LVLAX-GRS, LVSAX-GCS, LVSAX-GRS and global longitudinal LA strain were all significantly lower in HCM patients with elevated NT-proBNP  HCM patients had elevated NT-proBNP levels. There were no significant differences in major clinical and conventional CMR characteristics between HCM patients with and without elevated NT-proBNP levels Table . HCM patNP Table , Fig. 1.NP Table . There wp = 0.0233). The presence of LGE was similar in both groups, but HCM patients with elevated hsTnT had a significantly higher extent of LGE  and LVSAX-GRS correlated significantly with hsTnT levels  Table . There wLAX-GLS, LVSAX-GRS and LALAX-GLS to be impaired in HCM patients compared to healthy controls despite normal LVEF in both groups (Table This study analyzed global myocardial strain patterns in all four cardiac chambers in patients with HCM by CMR-FT strain. The major findings were the following: first, we found LVps Table , Fig. 1.ps Table , 3. Thirps Table .LAX-GLS and LVSAX-GRS despite preserved LVEF in HCM patients compared to healthy controls. Although LVEF is by far the most important clinical measure of LV function [LAX-GLS and LVSAX-GRS provide incremental prognostic information to LVEF in ischemic and non-ischemic cardiac disease [We found significantly decreased median LVfunction , it tendfunction . Therefofunction . Moreove disease , 21 and  disease . We susp disease  and scar disease  could exIn contrast, we found RV-GLS to be higher in HCM compared to controls Table . RV func2CH-GLS and LA4CH-GLS were significantly lower in patients with HCM compared to controls. Quantification of LA Strain is a sensitive marker of LV diastolic dysfunction independent of LVEF [2CH-GLS and LA4CH-GLS may not only reflect diastolic LV dysfunction in HCM but could also serve as an early predictor of HF and atrial fibrillation risk in HCM patients. Longitudinal studies are necessary in this context. However, we did not find significant difference in RA-GLS between HCM and controls (Table We found that LA of LVEF . In our  of LVEF . It is a of LVEF . Taking ls Table . Median NT-proBNP is a major cardiac biomarker, that is not only used to diagnose HF  but alsoLAX-GRS and LVSAX-GCS were affected by a poor and moderate inter-observer agreement in our study population, respectively. However, there were good to excellent inter-observer agreements for all other CMR-FT-derived measurements in this study population, which supports the reliability of the major findings of this work.This study is a retrospective study with its inherent limitations, such as missing values of cardiac biomarkers in some patients. Furthermore, this study did not include longitudinal, follow-up data and is, therefore, not designed to address a potential incremental value of CMR-FT strain over conventional imaging. Future longitudinal studies are needed to assess a potential incremental prognostic value of CMR-FT over conventional imaging such as the assessment of diastolic dysfunction by echocardiography. To date, CMR-FT strain is often used in addition to conventional imaging parameters since there is currently no clinical application with immediate individual benefit for patients. In particular, there is a substantial overlap in some strain parameters between HCM patients and controls. However, strain reflects the myocardial deformation process much more accurately compared to conventional imaging and may therefore contribute to a better understanding of subclinical pathophysiological myocardial alterations. In addition, T1-mapping/ECV imaging was not available before 2011 in this study population. Therefore, we were not able to systematically address potential associations between strain parameters and quantitative tissue characterization in this study. Long-axis-based GLS is currently perceived as the most robust and reproducible CMR-FT parameter, but the reproducibility of other strain parameters can differ significantly , 35. We CMR-FT reveals LV and LA dysfunction in HCM patients despite normal LVEF. The association between impaired LV strain and elevated NT-proBNP and hsTnT levels indicates a link between unapparent functional abnormalities and disease severity in HCM.


A amiloidose por transtirretina (ATTR) é uma doença familiar causada por uma das mais de 100 mutações descritas, em que há produção de amiloides que se depositam nos tecidos.,A síncope  na presença de cardiopatia, confere risco de eventos fatais.Homem, 64 anos, branco, engenheiro, natural do Rio de Janeiro. Relatava episódio isolado de síncope ao levantar-se rápido da posição sentada, após corrida. Histórico de morte súbita na família (tio aos 60 anos). Usava escitalopram 10 mg/dia e finasterida 5 mg/dia.2 e turgência jugular a 45°. PA: 140x80 mmHg, FC: 85 bpm, FR: 18 ipm, quarta bulha, ictus sustido e palpável no 6º espaço intercostal na linha hemiclavicular, pulmões limpos e edema de tornozelos. Vinha em CF I.Exame físico: IMC de 21,8 Kg/mSangue: peptídeo natriurético do tipo B (BNP): 233 pg/ml (VN: até 100 pg/ml) e Troponina US: 0,135 ng/ml .Eletrocardiograma (ECG) : ritmo s2 (Ecocardiograma (ECO TT): hipertrofia ventricular esquerda (HVE) - septo = 16 mm e parede posterior = 13 mm - fluxo mitral com déficit de relaxamento tipo II e volume indexado do átrio esquerdo: 87 ml/m2 . Holter strain global longitudinal (SGL), após RMC, mostrou alterações marcadas nas porções basal e medial de todas as paredes do miocárdio, poupando as regiões apicais do VE, o que era compatível com padrão descrito de amiloidose cardíaca (AC).Solicitada ressonância magnética do coração (RMC) em repouso e após estresse com dipiridamol, que mostrou HVE difusa e ausência de isquemia miocárdica, com áreas de realce tardio (RT) mesocárdico lateral e anterior e subendocárdico difuso no ventrículo esquerdo (VE), nos átrios e no septo interatrial . AvaliaçA biópsia de gordura abdominal e reto confirmaram o diagnóstico de amiloidose, pela coloração vermelho congo. Imunofixação no sangue e na urina de 24 horas e dosagem de cadeias leves no sangue afastaram gamopatia monoclonal, sendo solicitada, após isso, cintilografia miocárdica (CM) Pirofosfato de 99m-Tecnécio , que mosPor fim, o paciente foi submetido a teste genético, o qual confirmou mutação em heterozigose para o gene da transtirretina (TTR) do tipo Val142Ile.,,Quando se avalia um paciente vítima de síncope, é prioritária a estratificação do risco de eventos fatais,O BNP e a troponina elevados traduziam aumento de pressões intracavitárias e injúria miocárdica em curso, o que era indicativo de doença cardíaca.O ECO TT confirmou a suspeita de cardiopatia. As alterações encontradas , a histó,,A RMC, solicitada a seguir, forneceu evidências fortemente sugestivas de AC, dado ao padrão característico do RT, afastando as hipóteses de MCPH e de DAC. Por ser o gadolíneo um agente puramente extracelular e não penetrar no cardiomiócito intacto, a aparência característica do RT  em terriA avaliação da deformidade miocárdica pela técnica do SGL, realizada após a RMC, demonstrou um padrão típico de AC , o que p,,,Dentre os tipos de AC, a causada por cadeias leves de imunoglobulina (AL) é a que mais comumente acomete o coração, por isso, inicia-se a investigação pela busca de doença hematológica.Essa técnica é usada há tempos para diagnóstico de patologias ósseas, cujo radiotraçador tem grande afinidade pelo cálcio, o qual está presente, quase sempre, apenas nos depósitos da ATTR. Os valores preditivos positivos e negativos para o diagnóstico de ATTR pela CM com escore ≥ 2 é de 88 e 100% respectivamente. Propõe-se certeza diagnóstica quando há escore ≥ 2 na ausência de pico monoclonal de imunoglobulina, o que equivaleria à biópsia endomiocárdica,,Os sintomas cardiológicos mais frequentes na ATTR Val142Ile são: insuficiência cardíaca, dispneia, arritmias e tonteira. Síncope é um achado incomum (8%), mais frequente AL (20%), e quando acontece no esforço representa a inabilidade em aumentar o débito cardíaco, o que confere alta mortalidade.O THAOS, um registro mundial, aberto a todos os pacientes portadores de ATTR, mostra que a mutação Val142Ile  é a segunda mutação mais comum no mundo e a mais comum nos EUA, contabilizando 23% do total neste país e 1% do resto do mundo. Os portadores dessa mutação são, em sua maioria, afrodescendentes e homens, sendo prevalente em 3 a 4% de afroamericanos ao nascerem, com penetrância de aproximadamente 20%.,,A ATTR é uma causa subdiagnosticada de ICFEP, embora depósitos de TTR sejam identificados em até 30% de idosos encaminhados a autópsia. Transthyretin amyloidosis (ATTR) is a familial disease caused by one of more than 100 described mutations, where there is production of amyloids that are deposited in tissues.,Syncope  in the presence of heart disease confers risk of fatal events.The patient was male, 64 years old, of white ethnicity, engineer, born in Rio de Janeiro. He reported an isolated episode of syncope when he quickly got up from a sitting position after running. There was a history of sudden death in the family (uncle at 60). He used to take escitalopram 10 mg/day and finasteride 5 mg/day.2 and jugular turgency at 45o. BP: 140x80 mmHg, HR: 85 bpm, RR: 18 breaths per minute, fourth heart sound, sustained and palpable apex beat in the 6o intercostal space at the hemiclavicular line, clear lungs and ankle edema. He was in NYHA FC I. Blood: BNP: 233 pg/mL (NV: up to 100 pg/mL) and ultra-sensitive Troponin: 0.135 ng/mL (NV: up to 0.01 ng/mL).At physical examination: BMI of 21.8 kg/mThe electrocardiogram (EKG)  showed s2 (The transthoracic Echocardiogram (TTE) showed left ventricular hypertrophy (LVH) - septum = 16 mm and posterior wall = 13 mm - mitral flow with type II relaxation deficit and LA indexed volume: 87 mL/m2 . 24-h HoCardiac magnetic resonance imaging (CMRI) at rest and after stress with dipyridamole requested after TTE showed diffuse LVH and absence of myocardial ischemia, with areas of lateral and anterior mesocardial late enhancement (LE) and diffuse subendocardial LE in the LV, atria and interatrial septum . EvaluatAbdominal fat and rectal biopsies confirmed the diagnosis of amyloidosis with Congo red staining. Immunofixation in blood and 24-h urine and measurement of light chains Imunoglobulins in the blood ruled out monoclonal gammopathy, after which cardiac technetium-99m pyrophosphate scintigraphy (99mTc-PYP)  was requFinally, the patient underwent genetic testing, which confirmed a heterozygous Val142Ile mutation for the TTR gene.,,When evaluating a syncope patient, it is a priority to stratify the risk of fatal events,Elevated BNP and troponin levels reflected increased intracavitary pressures and ongoing myocardial injury, which was indicative of heart disease.The TTE confirmed the suspected heart disease. The , family ,,The CMRI, which was subsequently requested, provided evidence that was strongly suggestive of CA, given the characteristic LE pattern, ruling out the hypotheses of HCM and CAD. Because gadolinium is a purely extracellular agent and does not penetrate the intact cardiomyocyte, the characteristic appearance of LE  in non-cThe evaluation of myocardial deformity by the GLS technique, performed after the CMRI, demonstrated a typical pattern of CA , which r,,,Among the CA types, the one caused by light chains Imunoglobulins (AL) is the one that most commonly affects the heart; therefore, we began with the search for hematological disease.This technique has been used for a long time to diagnose bone diseases, of which radiotracer has a strong affinity for calcium, that is almost only present in ATTR deposits. Positive and negative predictive values for ATTR diagnosis by 99mTc-PYP myocardial scintigraphy with a score ≥ 2 are 88 and 100%, respectively. Diagnostic certainty is proposed when the score is ≥ 2 in the absence of an immunoglobulin monoclonal peak, which would be equivalent to a positive endomyocardial biopsy,,The most frequent cardiac symptoms in Val142Ile ATTR are: heart failure, dyspnea, arrhythmias and dizziness. Syncope, most frequently found in AL (20%), is unusual in ATTR (8%), and when it occurs on exertion it represents the inability to increase cardiac output, which confers high mortality.THAOS, an open worldwid registry to all patients with ATTR, shows that the Val142Ile, also known as Val122Ile mutation, is the second most common genotype worldwide and the most common in the USA, accounting for 23% of the total mutations in the country and 1% in the rest of the world. The carriers of this mutation are mostly of African descent and males, being prevalent in 3 to 4% of African-Americans at birth, with a penetrance of approximately 20%.,,ATTR is an underdiagnosed cause of HFpEF, although TTR deposits are identified in up to 30% of elderly patients referred for autopsy.


In some cases of vertebroplasty for adjacent fractures, we observed a cement bridging phenomenon, in which the injected cement flowed from the newly fractured vertebra to the previously cement-augmented vertebra through the space between the abutting anterior longitudinal ligament and the vertebral column. The purpose of this retrospective study was to investigate this phenomenon. From January 2012 to December 2014, patients who sustained new-onset adjacent vertebral compression fracture and who were again treated with vertebroplasty were enrolled. We divided the patients into two groups, the bridging group and the nonbridging group, to analyze the difference between them. Results showed that the cement bridging phenomenon occurred in 18 (22.8%) of the 79 patients. Significant differences between the bridging and nonbridging groups were identified in the following 3 imaging features: severe loss of the anterior vertebral body height at the new-onset adjacent vertebra on plain film , fluid accumulation  and hypointense signaling  around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI. After a 2-year follow-up, both the mean value of the focal kyphotic angle and anterior body height ratio were significantly better in the cement bridging group than in the nonbridging group. The cement bridging phenomenon, which has never been reported in the literature, is not rare in clinical practice. This phenomenon was associated with better maintenance of focal kyphotic angle and anterior body height ratio during the 2-year follow-up. Since then, this procedure has been used extensively worldwide for the treatment of osteoporotic vertebral compression fracture (VCF). The advantages of percutaneous vertebroplasty are that it is minimally invasive and efficient not only for providing pain relief and spinal stabilization but also for reducing the side effects of medications and the risks of long-term limited mobility4.Percutaneous vertebroplasty was first introduced in 1984 in France by Galibert for the treatment of a painful hemangioma at the C2 vertebral body7. The incidence of subsequent new-onset VCF after percutaneous vertebroplasty has been reported as 6.5–52% in the literature, usually occurring in adjacent vertebral bodies11. Secondary cement augmentation is an effective procedure for treating adjacent VCF12.However, some complications remain, such as cement leakage, pulmonary embolism and new-onset vertebral compression fractureDuring the procedure of percutaneous vertebroplasty for new-onset adjacent vertebral compression fracture, we observed a cement bridging phenomenon (CBP), in which the injected cement flowed from the newly fractured vertebra to the previously cement-augmented vertebra through the space between the abutting anterior longitudinal ligament and the vertebral column Fig. . This phBetween January 2012 and December 2014, all the patients in our institute were included in this study if they: (1) sustained new-onset adjacent vertebral compression fractures; and (2) were treated again with vertebroplasty. The local institutional review board approved this retrospective study  and waived the requirement for written informed patient consent. All methods were conducted in accordance with the relevant guidelines and regulations.The cement bridging phenomenon was defined as the presence of injected cement filling the newly fractured vertebra, flowing through the anterior margin of the spinal column, and then reaching the previously cement-augmented vertebra. The CBP was observed by orthogonal intraoperative fluoroscopy and confirmed by postoperative plain films. Each image was independent interpretated by two authors (YD Li and PL Lai) to reach agreement on the presence or absence of the CBP in one patient.Preoperative patient characteristics, including age, sex, body mass index (BMI), T-score of bone mineral density (BMD), findings from preoperative radiographic studies and MRI data, were recorded. The preoperative MRI analysis focused on both fluid accumulation or hypointense signaling around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc. The details of vertebroplasty were investigated, including the volume of injected cement and patterns of cement distribution. Postoperative data were reviewed, including the incidence rates of further adjacent fractures, serial changes in the anterior body height ratio of the newly fractured vertebra and the focal kyphotic angle Fig. , and cliAt the beginning of the procedure, the patient was placed in the prone position on the operating table. The surgical field and surgical drapes were carefully disinfected. After proper administration of local anesthesia, a vertebroplasty needle was inserted into the vertebral body through the pedicle under fluoroscopic guidance. After the needle was gently hammered into the anterior third of the vertebral body, preparation for the polymethylmethacrylate (PMMA) bone cement injection was initiated. The injection timing was chosen between the liquid phase and the paste phase of the bone cement. The injection was performed until symmetrical filling of the central and anterior parts of the vertebral body was obtained. Special attention was given to the flow of the bone cement while cement was distributed across the anterior margin of the spinal column.While the cement bridging phenomenon developed, the cement was continuously and cautiously injected. Injection typically ceased when cement reached the posterior quarter of the vertebral bodies (either the newly fractured vertebra or previously cement-augmented vertebra), leaked into veins, or leaked laterally out of osseous structures.It was suggested that all patients wear an orthosis when ambulating for 3 months. In general, antiosteoporosis medications and calcium and vitamin D supplementation were prescribed for the patients after surgery for osteoporotic VCFs. However, because of the potential adverse interaction with coexisting morbidities, antiosteoporosis medication was used on a case-by-case basis. These patients were usually discharged on the day of surgery or the next day and followed-up at 1 and 3 months postoperatively and then annually at outpatient clinics.p value < 0.05 was considered significant. Statistical analysis was performed using SPSS 25.0 . Power analysis was performed using the following parameters: test family—t tests, difference between two independent means (two groups), two-tailed, α = 0.05. .Associations between the cement bridging phenomenon and potential predictors were analyzed by the chi-square test or Fisher’s exact test for categorical variables and Student’s t test for continuous variables. Logistic regression analysis was used for the calculation of odds ratios and 95% confidence intervals. A A total of 79 patients (94 vertebrae) sustained new-onset adjacent VCF and then underwent further vertebroplasty. In 18 of 79 (22.8%) patients, or 20 of 94 (21.3%) adjacent vertebrae, the cement bridging phenomenon was observed. The mean age of patients who developed adjacent VCFs was 78.0 ± 6.3 years (range 66–95 years), and female patients made up the majority (87%). The most commonly involved vertebral level was T12 (36.2%), followed by L1 (21.3%) and L2 (16.0%).p < 0.05), which included severe loss (more than 50%) of the anterior vertebral body height at the new-onset adjacent vertebra on a lateral-view plain film , fluid accumulation  or hypointense signaling  around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI .The demographic data and the imaging features in the bridging and nonbridging groups are listed in Table There was no major complication that was directly attributable to vertebral augmentation in the bridging and nonbridging groups, such as epidural hematoma, pulmonary emboli, or cement leakage into the spinal canal.A total of 18 patients (20 vertebrae) in the bridging group and 56 patients (68 vertebrae) in the nonbridging group who had followed up for at least 2 years were enrolled for further analysis of clinical correlations.No statistical significance in the incidence rate of adjacent fractures was found between the bridging and nonbridging groups during 2-year follow-up. The incidence rates of adjacent fractures in the bridging group were 15.0%, 20.0%, and 20.0% at 3 months, 1 year, and 2 years postoperatively, respectively. The incidence rates of adjacent fractures in the nonbridging group were 14.7%, 17.7%, and 19.1% at 3 months, 1 year, and 2 years postoperatively, respectively.p < 0.05) at 3 months, 1 year, and 2 years postoperatively. The mean anterior body height ratio of the newly fractured vertebra was also significantly better (p < 0.05) in the cement bridging group than in the nonbridging group 1 year and 2 years postoperatively. The detailed values are listed in Table Compared with the nonbridging group, the cement bridging group demonstrated a significantly better mean value of the focal kyphotic angle (p = 0.812).Postoperatively, patients were scheduled to return for follow-up at 1 and 3 months after the surgery and then annually at outpatient clinics. However, some patients might visit the clinic more frequently than the scheduled follow-up if pain sustained. The number of patients who visited the outpatient clinics as scheduled follow-up and more frequently than the scheduled follow-up for the bridging group (n = 18) were 12 and 6; for the nonbridging group (n = 56) were 39 and 17, respectively. No statistical significance in the frequency of analgesics prescription in the outpatient clinics was found between the bridging and nonbridging groups during 2-year follow-up  is sometimes observed during the procedure of cement augmentation but has, to the best of the authors’ knowledge, not been published before. Due to the unknown mechanism and cause of formation, the cement bridging phenomenon usually presents unpredictably. When the phenomenon occurred, we were unclear about the clinical manifestation of this phenomenon. To solve this question, we tried to describe this phenomenon clearly, investigate the predictors of occurrence, and correlate the results with clinical application.The severe loss (more than 50%) in the anterior vertebral body height at the new-onset adjacent vertebra on plain film, fluid accumulation and hypointense signaling around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI were the three predictors of the CBP identified in this study. These three characteristics were presumed to be related to structural disruption anterior to the vertebral bodies and the corresponding intervertebral disc, indicating disruption of the anterior cortex and detachment of the anterior longitudinal ligament. The severe loss of anterior vertebral body height at the new-onset adjacent vertebra and hypointense signaling changes around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI suggest redundancy of the anterior longitudinal ligament. Therefore, an anterior intervertebral space existed, which may be related to the phenomenon of bone cement flowing from this space. Fluid accumulation around the space anterior to the abutting vertebral bodies and corresponding intervertebral disc results in the possibility of bone cement flowing from this space as well.13 proposed three patterns of cement leakage: (1) leakage via the basivertebral vein (B-type), (2) leakage via the segmental vein (S-type), and (3) leakage through a cortical defect (C-type). The cement bridging phenomenon develops leakage through a cortical defect, belonging to the C-type. Nieuwenhuijse et al.5 reported that the incidence of cortical leakage increased with advancing severity grade, which is consistent with the results of our research, that is, the severe loss of anterior vertebral body height was highly associated with the CBP.The cement bridging phenomenon is essentially an event of cement leakage because cement leakage has been defined as the presence of any extravertebral cement. Yeom et al.17 have shown that cement leakage into a disk is associated with adjacent VCFs. This made us wonder whether the CBP would also have a similar effect. However, there was no statistical significance in the incidence rates of secondary adjacent fracture between the bridging and nonbridging groups during the 2-year follow-up in our study. In fact, this issue is still inconclusive because several studies19 have demonstrated leakage unrelated to new fractures either at adjacent or non-adjacent levels. A meta-analysis conducted by Yi Zhan et al.20 mentioned that cement extravasation can also lead to serious complications including neurologic deficit and fetal sequalae such as pulmonary embolism, but it is generally of no clinical symptoms. Hassan et al.21 reported that there was no significantly difference in patient satisfaction between those who had cement extravasation and those who did not, in both groups.Some studiesIn spite of no major complication with regarding to the cement bridging phenomenon in our study, there was one case who developed lateral cement extravasation into paraspinal soft tissue during cement bridging phenomenon. This patient felt temporary paraspinal burning sensation during the cement curing process, and this symptom subsided completely after the procedure. In our opinion, leakage of bone cement to the lateral side is usually far more prone to produce symptoms than leakage to the front area. Faded color of the injected cement during the injection in the lateral view was usually a sign of lateral extravasation.22, but an alternative method is to fill these two neighboring vertebrae through one portal via the cement bridging phenomenon. To achieve this condition, we recommended to insert needles in these two neighboring vertebrae concurrently before cement injection. Then, we suggested to inject cement through the needle in the newly fractured vertebra first. Once CBP and cement filling in these refractured vertebrae developed, cement can be continuously injected with caution. If satisfactory filling pattern in the refractured vertebra was already achieved by this way, no further injection through the needle in the refractured vertebra was needed.Fourteen vertebrae (70%) that were previously cement-augmented demonstrated increased cement volume in the bridging group, which means that injected cement filled the newly fractured vertebra and the previously cement-augmented vertebra simultaneously via the cement bridging phenomenon. This finding was presumed to be related to the concurrent refracture of the previously cement-augmented vertebra and represented the real existence of the cement bridging phenomenon. Repeated percutaneous vertebroplasty for refracture of cemented vertebrae is a feasible treatmentp < 0.05) postoperatively in the cement bridging group than in the nonbridging group during the 2-year follow-up , which has never been reported in the literature, is not rare in clinical practice. The severe loss of anterior vertebral body height at the new-onset adjacent vertebra, fluid accumulation and hypointense signaling around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI were identified as predictors of the CBP. The cement extravasation could lead to complications, but may offer positive effect with occurrence of CBP through cautious control of cement injection. Cement bridging phenomenon was associated with better maintenance of focal kyphotic angle and anterior body height ratio during the 2-year follow-up.


Background and objectives: Childhood obesity has reached epidemic levels in the world. Obesity in children is defined as a body mass index (BMI) equal to or above the 95th percentile for age and sex. The aim of this study was to determine early changes in cardiac structure and function in obese children by comparing them with their nonobese peers, using echocardiography methods. Materials and methods: The study enrolled 35 obese and 37 age-matched nonobese children. Standardized 2-dimensional (2D), pulsed wave tissue Doppler, and 2D speckle tracking echocardiography were performed. The z-score BMI and lipid metabolism were assessed in all children. Results: Obese children  were characterized by enlarged ventricular and atrial volumes, a thicker left ventricular posterior wall, and increased left ventricular mass. Decreased LV and RV systolic and diastolic function was found in obese children. Atrial peak negative (contraction) strain , LV and RV global longitudinal strain , and LV global circumferential strain  were reduced in obese children. LV torsion  and normalized torsion  were greater in obese than nonobese children. A significant inverse correlation was found between LV and RV global longitudinal strain and BMI  and total cholesterol . Multivariate analysis revealed that the BMI z-score was independently related to LV and RV global longitudinal strain as well as LV circumferential and radial strain. Conclusion: 2D speckle tracking echocardiography is beneficial in the early detection of regional LV systolic and diastolic dysfunctions, with preserved ejection fraction as well as additional RV and atrial involvement, in obese children. Obesity may negatively influence atrial and ventricular function, as measured by 2D speckle tracking echocardiography. Obese children, though they are apparently healthy, may have subclinical myocardial dysfunction. Childhood obesity represents one of the most serious global public health challenges of the 21st century. In the WHO European Region, every third child is overweight or obese [Obesity in children is defined as a body mass index (BMI) equal to or above the 95th percentile for age and sex . In adulThe aim of our study was to assess atrial and ventricular systolic and diastolic function in obese children using 2D speckle tracking imaging, to correlate the values with traditional 2D echocardiographic measurements of atrial and ventricular function. We investigated the relationship between the variables of atrial and ventricular deformation and BMI, blood pressure, and lipid profile in obese and nonobese children.Of the 39 obese children without cardiovascular pathology admitted to the Department of Children’s Diseases, Lithuanian University of Health Sciences, between December 2016 and June 2018, four were excluded due to a poor acoustic window or having no suitable view for speckle tracking analysis. Thus, the study group consisted of 35 nonsyndromic obese children . Children in the study group had no history of smoking or clinical signs of cardiac disease, chronic illness, sleep apnea syndrome, diabetes mellitus, or hypertension. Their physical activity was normal (6–7 h/week). Their physical activity was evaluated by a survey of patients and their parents.Data of the children in the study group were compared with the data of 37 age-matched healthy children (control group); they had no medical complaints, no history of cardiac rhythm disturbance, they did not use any medications, and echocardiography was performed for a heart murmur. The study included children with normal findings of echocardiography. 2). Obesity was defined as when BMI, adjusted to the sex and age, exceeded the 95th percentile [Children were weighed in light clothes, using a Seca scale 711  with a capacity of 220 kg and accuracy of 100 g. Height was measured with a stadiometer (accuracy of 0.5 cm). The body surface area (BSA) was calculated according to the Dubois formula; BMI was calculated according to the formula: BMI = weight (kg)/height . Children and their parents gave their informed consent to perform a lipid profile. 2D echocardiography was performed using a commercial ultrasound system  with a 3.5-MHz transducer. A 3-lead electrocardiogram was taken throughout the examination. All images were recorded using harmonic imaging and stored digitally for analysis. The mean frame rate was 50 frames per second (range of 40 to 70 frames/s). Echocardiography and calculations of morphometric parameters were performed in accordance with the recommendations by the American Society of Echocardiography . The biplane Simpson’s method was used for the calculation of LV ejection fraction. LV and left atrial (LA) volumes were determined using the modified Simpson’s rule with images obtained from apical four-chamber and two-chamber views. Right atrial (RA) volume was obtained from an apical four-chamber view. A volumetric atrial assessment was performed at the end of systole, just before mitral valve opening, to assess maximal atrial volume, and at the end of diastole, after mitral valve closing, to assess minimal atrial volume. From these parameters, the total stroke volume  and total emptying fraction  were calculated . BMI, LV volumes, and LV dimensions z-scores were calculated based on the normal values of M-mode measurements ,11. The LV mass and atrial volumes were also indexed to body height raised to a power of 2.7.The diastolic function of LV and RV was assessed using pulsed wave Doppler. The peak velocities of mitral and tricuspid early filling (E) as well as late filling (A) waves, E/A ratio, and mitral E-wave deceleration time were measured. From the standard four-chamber view, the function of the LV and RV long axis was assessed using tissue Doppler imaging. The peak systolic velocity of mitral and tricuspid annulus , early diastolic velocity  and late diastolic velocity  were recorded and averaged over three consecutive cardiac cycles. The ratio of E/Em was calculated.The images obtained by conventional echocardiography were stored on the hard disc of the echocardiographic machine and transferred to a workstation  for offline analysis. A line was traced along the endocardium of LV and RV at the frame where it was best defined. The LV was divided into 6 long-axis segments in each view . The RV lateral wall was divided into basal, middle, and apical segments. For better visualization of the lateral wall of the RV and LV, children were asked to hold their breath. Radial and circumferential strain analysis was performed at the mitral valve, papillary muscle, and apical level in the parasternal short-axis view. For atrial analysis, a line was drawn along LA and RA endocardium, when the atria were at their minimal volume after contraction. The RA was divided into 2 (annular and middle) long-axis segments of the lateral wall, and the LA was divided into 4 long-axis segments (annular and middle) of the septum, lateral, anterior, and inferior walls. The superior or “roof” region of the atria was excluded, as this segment is rather stationary and makes no contribution to the atrial motion and active contraction. Three cardiac cycles were averaged. For the assessment of LV and RV long-axis function, mean global strain values were calculated. Closure of the aortic valve was identified as a sign of the end-systole. LA and RA long-axis function was assessed during atrial contraction , corresponding to atrial contractile function (peak negative strain), and during atrial relaxation , corresponding to atrial conduit function (peak positive strain). The sum of peak positive and negative strains was considered to be the total atrial strain, corresponding to atrial reservoir function . For the assessment of LV short-axis function, the images were scanned at the basis of the heart . The following parameters were calculated: global radial and circumferential strain, rotation of anterior septum, anterior, lateral, inferior, posterior LV walls and inferior LV septum. Data were subdivided into 6 segments for regional analysis at each ventricular level and averaged at the basal and apical level for the analysis of global rotational motion. Torsion  and normalized torsion   were alsp-value of <0.05 was obtained. The significance of inter-technique biases was tested using the paired t-test. Intraobserver measurements for ventricular and atrial strains were determined repeating the measurements of 2D speckle tracking echocardiography in 5 randomly selected subjects 1 month later. Intraobserver reproducibility was evaluated by means of the intraclass correlation coefficient (ICC). Differences were considered statistically significant when a The data were processed and analyzed using the IBM SPSS Statistics 22 package. n) and percentage (%). Student’s t-test was used to compare normally distributed data, and the Mann–Whitney test to compare non-normally distributed data. The Kolmogorov–Smirnov test was used in the investigation of hypotheses about the normality of the parameter distribution. Descriptive statistical data were presented as mean ± standard deviation (SD), median (interquartile range), number (n = 1/(∆2 + 1/N), where n is the sample size, ∆, the type error (0.05), and N, the population size. The calculated sample size was 35 children. We calculated the power of our study to substantiate the sample volume  hypothesis when the type I error α = 0.05). Statistical study power was calculated for both study groups based on weight, LV longitudinal strain, and LA minimal volume index using statistical tests. Study power was 0.99 in a total sample size of 72 subjects, with an alpha level of 0.05. The sample size was calculated using the formula Correlation analysis was performed using the Spearman correlation.p-value of <0.05 was considered statistically significant.To evaluate the independent influence of obesity, BP, HR, and lipids on echocardiographic parameters, stepwise multiple linear regression analysis was performed using LV longitudinal, circumferential, and radial strain, as well as RV longitudinal strain, as dependent variables. Statistical tests were two-sided, and a p < 0.001) as well as heart rate (p = 0.003), compared with control children. None of the obese children had a diagnosis of arterial hypertension, as their blood pressure (SBP and DBP) did not exceed the 90‰ BP percentiles according to age, sex, and height [p < 0.001).The main anthropometric, clinical, and lipid characteristics of the groups are shown in d height . The levp < 0.001), and enlarged LV end-diastolic volume (p = 0.04), while LV volume (end-diastolic and end-systolic) z-scores did not differ significantly between the groups. Higher values of indexed LV mass were found in obese children (p < 0.001).The conventional echocardiographic data are shown in p = 0.024, p = 0.004); significantly decreased early (Em) and late peak diastolic velocity (Am) of the septal mitral annulus ; significantly decreased late peak diastolic velocity (At) of the tricuspid annulus (p = 0.004)) in obese children. LV and RV early and late filling velocity, LV filling pressure (E/Em) was not different between groups. Tissue Doppler echocardiography revealed an impairment of LV and RV systolic and diastolic function  and the tricuspid annulus (St) (p < 0.001). LV global circumferential strain  was also significantly reduced in obese children. There was no significant difference in LV global radial strain between the groups . LV rotational parameters—torsion and normalized torsion—were significantly greater in obese than nonobese children . Significant inverse correlations were found between global LV and RV longitudinal strain and BMI , as well as between global LV and RV longitudinal strain and hypercholesterolemia . Ventricular deformation parameters are shown in p < 0.01). LA peak positive, total strain, RA peak negative and peak positive, and total strain did not differ between the obese and nonobese children. Volumetric analysis showed significantly increased minimal LAVi and RAVi  (p < 0.001) as well as maximal LAVi and RAVi (the volume indexes at the end of systole) (p < 0.001) in obese children. RA reservoir volume, indexed to BSA, was higher in obese children, while LA reservoir volume, indexed to BSA, did not differ between groups. Interestingly, significantly higher values of LA and RA reservoir volume indexes, also indexed to their height raised to the power of 2.7, were found in obese children (p < 0.001). LA and RA stroke volume was significantly increased in obese children . Although the total emptying fraction did not differ between groups, it tended to be smaller in the obese group.The volumetric LA and RA data, the values of LA and RA strain are shown in r = 0.506, p = 0.001 and r = 0.562, p = 0.001, respectively) as well as between LA reservoir volume and LV end-diastolic volume . A significant inverse correlation was observed between LA peak negative strain and BMI  as well as between LA peak negative strain and total cholesterol . No significant correlations between LA peak negative strain and LA volumes or indexes, LV parameters obtained by conventional or tissue Doppler echocardiography were observed.Significant correlations were found between LA and RA reservoir volume and BMI  for LV longitudinal strain and −0.1  for atrial peak negative strain.The data of our study provides additional support that childhood obesity is independently associated with changes in cardiac structure and function. The results show that obese children without comorbidities had a subclinical impaired atrial and ventricular systolic and diastolic function at a relatively early age (the age of the study group was 13.51 ± 2.15 years).Using conventional echocardiography, our findings were that obese children had a larger LV mass and LV posterior wall thickness, increased LV end-diastolic volume, increased LA and RA volume. Obesity is related to insulin resistance, water and salt retention, which leads to higher total blood volume and increased preload ,16,17. IIn line with other studies, our findings showed that obese children had increased heart rates and cholesterol levels compared to controls ,19. IncrOn the other hand, dyslipidemia, as a part of metabolic syndrome, is a metabolic factor influencing vascular changes . In our Assessing the systolic function of LV and RV by conventional echocardiography, the global LV ejection fraction (LVEF), tricuspid annulus motion amplitude did not differ between obese and nonobese children. Assessing the limitations of the conventional echocardiography measurement of LV and RV function , age-depAccording to the data obtained by 2D speckle tracking echocardiography, LV and RV global longitudinal, as well as LV global circumferential, strains were significantly decreased in obese children. We found lower strain values in obese children using this technology, compared to the works by other authors ,22,24,25The results of our study are consistent with the findings of previous studies that analyzed LV and RV systolic long-axis function. Longitudinal strain assessed in obese children and young adults without high blood pressure was reduced, compared with healthy children ,26,27,28Changes in longitudinal strain may be observed due to affecting the subendocardial layer . The reaIn the present study, only radial strain values, derived from 2D speckle tracking echocardiography, were comparable in obese and nonobese children. The proposed mechanism for this was described by Saltijeral et al. as a compensation mechanism to maintain contractility at an early stage of obesity cardiomyopathy .This explains that “normal” LVEF was not equal to normal systolic function, as compensatory mechanisms in different strain directions can preserve global EF. In the early stages of heart disease, there is a reduction in the longitudinal myocardium contraction; in the later stages, reduction in the circumferential and radial contractions occurs and leads to a reduced LVEF ,30. LV morphological alterations observed in our study have shown that LV remodeling determines functional LV impairment. Decreased global circumferential strain, as well as increased apical rotation and torsion, were indicators of impaired diastolic function in obese children. LV torsion is after-load dependent, and a chronic increase in afterload leads to increasing apical rotation and LV torsion ,16. InteDespite weak correlations between LV and RV global longitudinal strain and BMI, our study showed that BMI was independently related to LV and RV longitudinal, LV circumferential, and LV radial strains. These results are consistent with the data of previous studies, where BMI was an independent predictor of worsening LV and RV systolic and diastolic function ,5,24. Since atrial function is influenced by ventricular geometry and function, we evaluated atrial function using conventional and 2D speckle tracking echocardiography. In our study, we expected an increase in atrial strain as a result of volume overload, but conversely, we found a significant reduction of LA strain in contraction among obese children. This means that contractile atrial function is impaired in obese children. When LA enlargement exists, it would be clinically helpful to have parameters that could distinguish normal from impaired LA contractile function. LA contractile function is dependent on preload stretch and afterload, represented by LV end-diastolic pressure . However, in our study, LA and RA strain in relaxation  did not differ between groups. These findings contradict the results of a study by di Salvo et al.  who repoThe results of our study suggest a weak association between early myocardial dysfunction in obese children. These findings suggest turning clinicians’ attention to the importance of obesity treatment and weight loss in childhood as early as possible. 2D speckle tracking echocardiography could help assess the potential reversibility of myocardial dysfunction during obesity treatment with a return to normal weight.The most important limitation of the study was the small cohort. Another limitation of our study was an incomplete metabolic profile  in both obese and nonobese children, as a metabolic abnormality exerts an independent effect on cardiac function. Physical activity was measured merely by a survey of patients and their parents, without using any validated instrument. Data on the renin-angiotensin-aldosterone system and the sympathetic nervous system were not investigated. Additionally, the study design does not allow providing information about the potential reversibility of the changes with weight loss over time. Larger-scale, long-term studies are necessary to confirm the clinical importance of these study results.2D speckle tracking echocardiography is beneficial for the early detection of regional LV systolic and diastolic dysfunction with preserved ejection fraction, as well as additional RV and atrial involvement in obese children. Obesity (BMI above the 95th percentile) may negatively influence atrial and ventricular function, measured by 2D speckle tracking echocardiography. Our results support that obese children, despite their being apparently healthy, may have subclinical myocardial dysfunction.


We describe the case of a young man with an initial diagnosis of acute myocarditis that was finally recognized as a familial left-dominant arrhythmogenic cardiomyopathy. The diagnostic process was also based on demonstration, serial cardiac magnetic resonance imaging, and typical patterns of myocardial damage, including features of the disease’s inflammatory “hot phase”. Arrhythmogenic cardiomyopathy is currently defined as a (genetic or non-genetic) heart muscle disorder characterized by progressive ventricular myocardial damage with fibrofatty replacement, which may represent the substrate for malignant ventricular arrhythmias . AlthougA 23-year-old man was admitted to our cardiomyopathy clinic for repetitive ventricular ectopic beats. He was hemodynamically stable with no other relevant symptoms. He never experienced syncope and was unaware of any case of cardiomyopathy or sudden cardiac death in his family. Remarkably, his medical history included an episode of acute myocarditis one year before. At that time, he was admitted to the emergency department of a different hospital with chest pain, troponin rise, and T wave inversion in the inferolateral leads on ECG . An urgeTo exclude a left-dominant variant of arrhythmogenic cardiomyopathy, in which this LGE pattern has been reported with CMR, genetic testing and accurate family screening were then performed. His 56-year-old mother and 30-year-old sister, both asymptomatic, were also found to have inverted T waves in the inferolateral leads on ECG and a mildly reduced LV EF on echocardiogram. Performing CMR on those two subjects, a pattern of LGE very similar to the one detected in the proband was detected . No releMolecular testing was carried out by analyzing a panel of target genes through an NGS-based procedure. The MAF threshold was set to 5% using Illumina Variant Interpreter Software. Genetic testing identified a heterozygous variant in DSP .According to the American College of Medical Genetics (ACMG), the variant was classified as likely pathogenic (class IV).The same mutation was found in the patient’s relatives with a positive phenotype , and a dDesmosomes are specialized adhesion junctions. They provide mechanical connections between cardiomyocytes and mutations in gene encoding proteins involved in the desmosome apparatus , and have been identified as responsible for arrhythmogenic cardiomyopathy in about 50% of cases . In affeIn cases of arrhythmogenic cardiomyopathy associated with DSP mutation, as compared to other genetic patterns, the phenotypic expression tends to include a more common and severe LV involvement ,7. In thDuring the last decades, a possible role for inflammation in the development and progression of myocardial damage in patients with DSP mutations has been postulated, supporting the hypothesis that inflammatory dysregulation could contribute to phenotypic disease progression . In termhot phases of the disease that in many cases resemble episodes of acute coronary syndrome or myocarditis.Recent observations further support the existence of a peculiar form of arrhythmogenic cardiomyopathy in patients with DSP mutations, presenting a clinical course that frequently includes episodic myocardial injuries, anticipating the occurrence of LV myocardial fibrosis, and dysfunction ,15. DeteThe use of steroid treatment is well supported in the context of fulminant myocarditis related to a specific disease , while the benefit of immunomodulatory therapies has not shown any benefit in long term outcome studies in patients who have not performed endomyocardial biopsy .A recent study  demonstrDespite compelling evidence indicating the role of inflammation in ACM, immunomodulatory therapies are seldom used. In a small case series of pediatric AC patients, a decrease in hospital stay was demonstrated, although steroid therapy seemed not to prevent disease progression or affect outcomes . There ahot phase of genetically-determined arrhythmogenic cardiomyopathy. High accuracy and reproducibility in the assessment of ventricular morphology and function, together with the ability to provide tissue characterization, make CMR the ideal technique in assisting the diagnosis of both arrhythmogenic cardiomyopathy and myocarditis. To correctly guide further management, the possibility of an association between these two conditions should be kept in mind when performing serial CMR scans after a clinically evident episode of acute non-ischemic myocardial damage.The present report highlights the possibility that clinically suspected acute myocarditis may represent, instead, the


In our everyday practice with COVID-19 patients, we noticed that they are not tachycardic even when critically ill and shocked on pressors they are bradycardic. Most of them are in sinus rhythm. However, some of them go into advanced degree heart block and had cardiac arrest related to complete heart block. A 72-year-old female with a history of hypertension and diabetes admitted with COVID-19 bronchopneumonia. The hospital course has been complicated by respiratory failure requiring mechanical ventilation and septic shock requiring norepinephrine. It was noted that she is bradycardic in the 50s in sinus rhythm, her heart rate dipped down to 30 for about six seconds, and her telemetry strip showed evidence of complete heart block, and then she was back in sinus rhythm. The decision was made to follow-up, given that it was for a short time and did not recur. The next day she had cardiac arrest related to a complete heart block, and a temporary trans-venous pacemaker was placed, Later when her condition improved, her heart rate started recovering gradually. At first, she was in junctional tachycardia, and one week later, she was back in sinus rhythm. The temporary pacemaker was removed, and she was discharged on a ZIO monitor for two weeks with no further evidence of bradycardia. Bradycardia in COVID-19 patients is frequently reported. It is not always benign and should be managed promptly when there is evidence of advanced heart block. In our ICU at Rochester General Hospital, we noticed that most COVID patients are bradycardic. Bradycardia sometimes even affects our decision when choosing what vasopressor to use while they are in shock. Bradycardia is frequently described in the literature, but complete heart block and cardiac arrest related to COVID are not frequently delineated. We are shining the light on a case of complete heart block related to COVID-19.A 72-year-old female with a past medical history of hypertension and diabetes was admitted with COVID-19 bronchopneumonia. Her hospital course has been complicated by respiratory failure requiring mechanical ventilation, septic shock requiring norepinephrine. During the admission, she was bradycardic in the 50s in sinus rhythm. Her heart rate dropped down to 30 for a short time of about six seconds. The rhythm strip showed AV dissociation consistent with complete heart block, as shown in Figure The bradycardia episode did not last long enough to obtain 12 lead EKG. She was then back in sinus rhythm. Her transthoracic echocardiography was unremarkable with normal ejection fraction and no segmental wall motion abnormality, brain natriuretic peptide (BNP) within normal limits, troponin I elevated up to 50 ng/ml. Troponin elevation was attributed to demand-mediated myocardial ischemia.The decision was made to follow up, given that the complete heart block was for a short time and did not recur. The patient was not on any medication or sedation that can cause bradycardia and was oxygenating well on the ventilator. The next day she had pulseless electrical activity (PEA) cardiac arrest related to complete heart block, and return of spontaneous circulation (ROSC) was achieved after three minutes, and a temporary trans-venous pacemaker was placed, and she was paced most of the time because of persistent bradycardia and complete heart block. Later, when her condition improved and she was extubated, her heart rate started recovering gradually. At first, she was in junctional tachycardia, as shown in Figure She remained in hospital because of poor physical condition and need for rehabilitation placement, and all that time, she was on continuous telemetry. One week later, she was back in sinus rhythm, as shown in Figure Multiple bradyarrhythmias and tachyarrhythmias had been described to happen in COVID-19 patients. Sinus bradycardia also had been described frequently [The pathogenesis of bradycardia remains poorly understood; multiple proposed mechanisms include increased vagal tone , direct The treatment is still according to advanced cardiac life support (ACLS) guidelines for symptomatic bradycardia. According to the European Society of Cardiology/American Heart Association (ESC/AHA) guidelines, if an advanced degree of heart block is found, for example, Mobitz type II and higher or if the bradycardia is causing hemodynamic instability or is symptomatic, this became very unstable. Temporary pacing should be done to prevent potential deterioration resulting in hemodynamic instability or cardiac arrest, as seen in this case. In our opinion, the complete heart block could be related to COVID myocarditis given that the patient had bradyarrhythmia with significant troponin elevation in the absence of segmental wall motion abnormality and that it resolved with the resolution of COVID as demonstrated in this case but still difficult to prove and needs to be further studied.The main message is to keep in mind that despite that bradycardia in COVID-19 patients is frequently reported, it is not always benign and should be managed promptly when there is evidence of advanced heart block.


Background: Congenital heart disease (CHD) with single-ventricle (SV) physiology is now survivable with a three-stage surgical course ending with Fontan palliation. However, 10-year transplant-free survival remains at 39–50%, with ventricular dysfunction progressing to heart failure (HF) being a common sequela. For SV-CHD patients who develop HF, undergoing the surgical course would not be helpful and could even be detrimental. As HF risk cannot be predicted and metabolic defects have been observed in Ohia SV-CHD mice, we hypothesized that respiratory defects in peripheral blood mononuclear cells (PBMCs) may allow HF risk stratification in SV-CHD.Methods: SV-CHD (n = 20), biventricular CHD , or healthy control subjects (n = 22) were recruited, and PBMC oxygen consumption rate (OCR) was measured using the Seahorse Analyzer. Respiration was similarly measured in Ohia mouse heart tissue.Results: Post-Fontan SV-CHD patients with HF showed higher maximal respiratory capacity (p = 0.004) and respiratory reserve (p < 0.0001), parameters important for cell stress adaptation, while the opposite was found for those without HF . This was observed in comparison to BV-CHD or healthy controls. However, respiration did not differ between SV patients pre- and post-Fontan or between pre- or post-Fontan SV-CHD patients and BV-CHD. Reminiscent of these findings, heart tissue from Ohia mice with SV-CHD also showed higher OCR, while those without CHD showed lower OCR.Conclusion: Elevated mitochondrial respiration in PBMCs is correlated with HF in post-Fontan SV-CHD, suggesting that PBMC respiration may have utility for prognosticating HF risk in SV-CHD. Whether elevated respiration may reflect maladaptation to altered hemodynamics in SV-CHD warrants further investigation. Hypoplastic left heart syndrome (HLHS) is a critical congenital heart disease (CHD) characterized by hypoplasia of left-sided structures of the heart, including the ascending aorta, left ventricle (LV), and aortic and mitral valves. As there is only a single pumping chamber in HLHS [the right ventricle (RV)], it is a type of single-ventricle (SV) CHD. While HLHS and other SV-CHDs were previously uniformly fatal, it is now survivable with a three-stage surgical palliation that includes the final Fontan surgery. Together, this creates an SV circulation with venous blood routed directly to the lungs by gravity, while the single pumping chamber (LV or RV) serves as the systemic chamber pumping blood to the rest of the body .While such SV physiology  allows mOur previous study of a mouse model of HLHS  uncovereBased on these previous findings, in the present pilot study, we investigated the hypothesis that respiratory parameters in PBMC may have prognostic value for assessing HF risk in SV-CHD. For this study, we recruited SV-CHD patients pre- vs. post-Fontan completion and also age-matched BV-CHD patients and control subjects.CHD patients and healthy control subjects were recruited from the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC) under a human study protocol approved by the University of Pittsburgh Institutional Review Board. Informed consent was obtained, and for infants and minors, informed consent was obtained from the parent or legal guardian. Recruitment criteria comprised subjects with complex SV-CHD or BV-CHD. For SV-CHD, this included HLHS, critical aortic stenosis, pulmonary atresia with intact ventricular septum, double outlet RV with mitral atresia, and unbalanced atrioventricular septal defect with total or partial anomalous pulmonary venous return, while BV-CHD included Tetralogy of Fallot, transposition of the great arteries, Ebstein's anomaly, aortic arch hypoplasia, aortic stenosis, ventricular septal defect, and pulmonary stenosis. Three pediatric dilated cardiomyopathy (DCM) patients with HF were recruited as BV-HF disease controls, two having received a heart transplant and the third listed for transplant and having received an interim ventricular assist device. Patient demographics are summarized in 2 pieces of heart tissue were plated into individual wells of a Seahorse XF24 microplate, and OCR was measured using the same Seahorse XF Cell Mito Stress Kit without stimulation during two cycles of measurement.Whole blood was used to recover fresh PBMCs using standard protocol with Ficoll-Paque PLUS from Pharmacia Biotech (or a similar separation medium). After centrifugation, PBMCs at the interphase were collected, washed twice, and resuspended in RPMI 1640 with 10% fetal bovine serum, and the cells were counted. For measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), 20,000 PBMCs were seeded into each well of a Seahorse XFe96 plate. OCR and ECAR were determined using the Seahorse XF Cell Mito Stress Kit (Agilent). Basal respiration was measured in unstimulated cells. Afterward, oligomycin (1 μM) was added to quantify respiration coupled to ATP production and proton leak followed by carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone  injection to assess maximal cellular respiration (respiratory capacity). Finally, antimycin A (1 μM) and rotenone (1 μM) were used to assess non-mitochondrial respiration. For mouse heart tissue, OCR was obtained for the quantification of basal respiration. For this analysis, 2-mmn = 16) or SV-CHD (n = 20) and 22 healthy controls without CHD were recruited with informed consent, and blood samples were obtained for PBMC isolation. Among the 20 SV-CHD patients, 16 had HLHS with dominant/systemic RV, and four had dominant/systemic LV (CHD patients with BV-CHD (temic LV . Twelve temic LV . Of the temic LV .n = 16) patients and 15 of the 20 SV-CHD patients survived heart transplant-free and were classified as having a favorable clinical outcome without HF. Among the SV patients, five HLHS patients had an unfavorable cardiac outcome related to HF, one having died from acute HF, and four exhibiting cardiac death. The latter was indicated by having had a heart transplant (n = 3) or having been listed for heart transplant for decompensated HF (n = 1). Using the New York Heart Association (NYHA) HF classification, the four HLHS patients ≥10 years old with HF had significantly higher or worse NYHA scores than either the BV-CHD patients (p = 0.014) or the SV-CHD patients with favorable outcome (p = 0.005) (All of the BV-CHD (= 0.005) .PBMCs isolated from the blood of patients and controls were analyzed for OCR using the Seahorse Analyzer. Measurements of the different mitochondrial respiratory parameters were obtained by assessing the changes in OCR with the addition of different inhibitors of respiration. No significant difference in OCR was observed among the control subjects stratified by age, although a trend for lower OCR was observed in patients >40 years old . This isComparisons between the SV-CHD and BV-CHD patients showed no difference in mitochondrial respiration . A similComparison of the pre-Fontan (<1 year old) vs. post-Fontan (>10 years old) SV or HLHS patients showed no difference in mitochondrial respiration . ECAR daOf the eight SV-CHD patients with Fontan completion, four had HF. These patients showed a significantly higher OCR when compared to those of SV-CHD patients without HF, BV-CHD patients, or healthy controls . These cGiven that SV-CHD with systemic RV is known to have worse clinical outcome than SV-CHD patients with systemic LV –10, we rTo further investigate whether the increase in respiration in the SV-CHD patients with HF may be attributable to HF in general, we recruited three pediatric DCM patients with HF and obtained PBMCs for a similar analysis of mitochondrial respiration. However, no significant difference was observed in the mitochondrial respiration of the DCM patients with HF vs. the BV-CHD patients without HF . We alsoOhia mouse line were previously shown to suffer early HF with severe pericardial effusion  can be found at: NCBI [accession: The studies involving human participants were reviewed and approved by University of Pittsburgh Institutional Review Board. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. The animal study was reviewed and approved by University of Pittsburgh Institutional Animal Care and Use Committee. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.CL, XX, and J-HL contributed to the study design. CL and J-HL contributed to the recruitment of subjects and human blood sample collection. XX contributed to the PBMC isolation. XX, MR, SS, and ZK contributed to the Seahorse measurement. TT, XL, and XX contributed to the mouse fetal ultrasound imaging and mouse phenotyping. GG and XX contributed to the mouse embryo dissection. AB and XX contributed to the mouse RNA-seq and data analysis. XX contributed to the statistics. CL, XX, J-HL, and SS contributed to the manuscript preparation. All authors contributed to the article and approved the submitted version.This work was supported by NIH grants HL132024 and HL142788 (CL), UPMC Fellows Grant (XX), and American Heart Association/ Children's Heart Foundation postdoctoral fellowship (XX) and support from Department of Critical Care Medicine (J-HL).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To assess the prognostic value of early echocardiographic indices of right ventricular function and vasoactive peptides for prediction of bronchopulmonary dysplasia (BPD) or death in very preterm infants.Prospective study involving 294 very preterm infants , of whom 57 developed BPD  and 10 died. Tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) were measured on day 7 of life.rS -0.182 to 0.359) and predicted BPD/death with similar accuracy (areas under receiver operator characteristic curves 0.62 to 0.77). Multiple regression revealed only RIMP and birth weight as independent predictors of BPD or death.RIMP was significantly increased (median [IQR] 0.3 [0.23–0.38] vs 0.22 [0.15–0.29]), TAPSE decreased (median [IQR] 5.0 [5.0–6.0] vs 6.0 [5.4–7.0] mm), MR-proANP increased (median [IQR] 784 [540–936] vs 353 [247–625] pmol/L), and CT-proET1 increased (median [IQR] 249 [190–345] vs 199 [158–284] pmol/L) in infants who developed BPD or died, as compared to controls. All variables showed significant but weak correlations with each other (Vasoactive peptide concentrations and echocardiographic assessment employing standardized measures, notably RIMP, on day 7 of life are useful to identify preterm infants at increased risk for BPD or death. Despite major advances in perinatal care, the prevalence of bronchopulmonary dysplasia (BPD) remains high, presumably due to the improved survival of extremely low gestational age infants –3. BPD iEarly prognostication of the BPD risk is desirable in order to adapt clinical management and to identify high-risk infants potentially eligible for inclusion in early-phase therapeutic trials. However, prediction of BPD development is difficult due to the complex pathophysiology of the disease including genetic and perinatal risk factors.Pulmonary hypertension complicates BPD and contributes significantly to increased morbidity and mortality rates in infants with BPD . Thus, eRecognizing the important role of early pulmonary vascular disease in BPD pathophysiology, we aimed to explore the role of vasoactive peptides implicated in pulmonary hypertension and echocardiographic markers of right ventricular (RV) function in preterm infants. In recent studies, right ventricular index of myocardial performance (RIMP) as well as tricuspid annular plane systolic excursion (TAPSE) appeared to be promising echocardiographic indices for identification of infants with subsequent BPD development ,13. The In the current study, we hypothesized that the echocardiographic indices RIMP and TAPSE and the plasma biomarkers mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) measured on day 7 of life predict subsequent respiratory morbidity in preterm infants. The aims of the present study were 1) to investigate the ability of the above-mentioned echocardiographic indices and biomarkers to predict BPD at 36 weeks postmenstrual age (PMA) or death and 2) to test their association with prolonged respiratory morbidity i.e. duration of supplemental oxygen and duration of respiratory support.This prospective observational study was conducted in two tertiary care perinatal centers at University Children’s Hospital Basel, Switzerland and Charité Universitätsmedizin Berlin, Germany. Preterm infants with a gestational age (GA) < 32 weeks were considered eligible for the trial. Exclusion criteria were congenital heart disease, congenital diaphragmatic hernia, esophageal atresia, or infants who died during the first week of life. All infants received intensive care based on local standard operating procedures and were examined without sedation in a supine position.The study protocol was approved by both local institutional review boards  and written informed parental consent was obtained before enrollment.Perinatal variables and patients’ characteristics were collected from each infant’s chart, including BPD defined as a requirement for supplemental oxygen to maintain preductal arterial oxygen saturations of 92% at 36 + 0 weeks PMA ,20. PrimEchocardiography was performed in Berlin using an Epiq 7G system with an S8-3 probe , or a Vivid S6 system with a 6S probe , and in Basel using a Mindray ZONARE Z.One PRO ultrasound machine with a 3–10 MHz transducer . All scans were performed by experienced operators .We performed transthoracic echocardiography on day of life (DOL) 7 (± 2) days. The presence or absence of a patent ductus arteriosus (PDA) was determined by direct ductal imaging in the high left parasternal view with color Doppler mapping. TAPSE and RIMP were used to assess RV function. RIMP was measured by conventional pulsed Doppler using the method proposed by Tei et al. . TherefoBlood samples of 500 μL were drawn on DOL 7 (± 2 days) in EDTA tubes simultaneously with routine blood sampling. The samples were immediately transferred to the central laboratory of both study sites for centrifugation and storage at -80°C. Analyses for levels of MR-proANP and CT-proET1 were performed in batches using an automated immunofluorescent assay  ,24.Aiming for 85% power at the 5% significance level, we calculated a minimum required sample size of n = 292 using a multivariable linear regression model with duration of supplemental oxygen as the independent variable and the RIMP as the dependent variable, adjusting for demographic parameters birth weight, sex, growth retardation, and sepsis.2-test or Fisher’s exact test as appropriate. Spearman rank correlation coefficients rS were calculated to investigate the relationship between echocardiography parameters and vasoactive peptide concentrations. We performed logistic regression analysis with stepwise backward elimination of non-significant variables. The predictive values of RIMP, TAPSE and vasoactive peptides were estimated by the areas under receiver operating characteristic (ROC) curves. We investigated the association of echocardiographic indices and vasoactive peptides with duration of supplemental oxygen by univariable and multivariable linear regression analysis with stepwise backward elimination of non-significant variables. A P-value of < 0.05 was considered to be statistically significant.SPSS software version 25.0  was used for statistical analysis. Patient characteristics and all measured data are reported as medians and interquartile ranges (IQR) or n (%) and compared using the Mann-Whitney U-test, Kruskal-Wallis test or ChiA total of 294 preterm patients  were included into our study during January 2015 and November 2017. The recruitment flow chart can be found in P < 0.01). The rate of fetal lung maturation by antenatal corticosteroid administration (considered complete if the mother had received two injections of 12 mg betamethasone 24 hours apart and more than 24 hours before delivery) was higher in non-BPD infants (P < 0.01). Preterm infants with BPD/death received significantly longer mechanical ventilation and supplemental oxygen, and stayed longer in hospital (P < 0.01 for each factor). Ten infants died, seven of these had a fulminant sepsis, two patients died secondary to abdominal complications and one patient died from respiratory failure.About half of enrolled patients were male or required mechanical ventilation and 22% developed BPD. None of the infants received sedative, vasoactive or inotropic drugs when measurements were performed on DOL 7. Treatment for hemodynamically significant PDA with Indomethacin or Ibuprofen was performed in 55 (19%) infants at a median (IQR) age of 10 (7–16) days. BPD/death infants had a significantly lower GA and birth weight (P < 0.001). Both vasoactive peptides (MR-proANP and CT-proET1) were significantly higher in BPD/death infants as compared to controls .Comparison of echocardiographic parameters and vasoactive peptides on DOL 7 between infants with BPD/death and without BPD are shown in rs) of RIMP with TAPSE, MR-proANP and CT-proET1. Vasoactive peptides were positively correlated with RIMP (P  < 0.001) and negatively correlated with TAPSE (P = 0.003), but all observed correlations were weak   .P < 0.001 and P = 0.012). Lower birthweight and higher RIMP values predicted BPD/death. The likelihood of developing BPD/death can be calculated using both parameters in the equation specified by the estimates of regression coefficients in In a logistic regression model with birth weight, RIMP, TAPSE, MR-proANP and CT-proET1 in the equation, only birth weight and RIMP were independent predictors of BPD/death . Receiver operating characteristic (ROC) curve analysis for the detection of BPD/death revealed that RIMP and TAPSE showed similar areas under the curve (AUC), MR-proANP the largest and CT-proET1 the smallest AUC  is secreted by stressed and distended atrial myocytes in response to volume and pressure load. Since pulmonary hypertension results in increased volume and pressure load, it is biologically plausible that elevated ANP levels are associated with BPD development.Endothelin-1 is a vasoactive peptide, which is most abundant in the lungs, secreted by endothelium, smooth muscle, airway epithelium, and a variety of other cells . SecretiEndothelin-1 causes vasoconstriction and is involved in pulmonary vascular disease and fibrosis. Since these features are hallmarks of BPD, Endothelin-1 is likely to play a role as an early marker of BPD development. However, multivariable analysis showed that elevated CT-proET1 levels on DOL 7 were not associated with BPD/death after correction for birth weight, RIMP, TAPSE and MR-proANP. Determination of CT-proET1 levels at different time points or in different population, e.g. focusing on extremely preterm infants might result in different findings.Strengths of our study include a relatively large sample size and the prospective two-center design. A potential limitation involves the rather low rate of preterm infants with moderate to severe BPD/death in our study (22%) which was lower than previously reported . A potenPrevention of BPD and its long-term sequelae remain elusive due to multifactorial origin and different disease endotypes . Early dEchocardiographic indices, in particular RIMP obtained on DOL 7, seem to be useful for early identification of preterm infants at high risk for BPD or death. This echocardiographic marker might help in the future to identify selected patients who might benefit from early prevention trials.S1 Dataset(XLSX)Click here for additional data file.


The purpose of our study was to compare diagnostic performance of old and new Lake Louise Criteria (oLLC and nLLC) among different clinical presentations: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR). 102 patients with clinical suspicion of acute myocarditis underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. Protocol included cine-SSFP, T2-weighted STIR, T2 mapping, early and late gadolinium enhancement and T1 mapping acquired before and after gadolinium administration. The degree of agreement has been calculated with Cohen’s K test. 42 patients also underwent endomyocardial biopsy (EMB). IL onset was present in 54/102 patients, CM in 28/102 and AR in 20/102. nLLC were positive in 58.3% of the patients, while oLLC in 37.9%, k = 0.57 (IC: 0.428–0.713). The degree of agreement between nLLC and oLLC was 0.49 (IC: 0.111–0.876) for AR onset (nLLC positive in 35% vs oLLC in 15%), 0.25 (IC: 0.035–0.459) for CM pattern (nLLC positive in 60.7% vs oLLC 17.9%) and 0.73 (IC: 0.543–0.912) for IL presentation (nLLC positive in 66.7% vs oLLC in 57.4%). Diagnostic accuracy was 75% for both nLLC and oLLC among IL onset, and 41.6% for oLLC vs 66.7% for nLLC, as regards CM clinical presentation. nLLC have improved diagnostic performance of CMR for the diagnosis of acute myocarditis, in particular for atypical clinical presentation. Clinical presentations of acute myocarditis (AM) vary through a wide range of manifestations , 2, affeEndomyocardial biopsy (EMB) still represents the gold standard for the diagnosis of acute myocarditis , that isIn 2009, Friedrich et al. defined the Consensus Criteria for CMR in myocardial inflammation, the so-called Lake Louise Criteria (LLC). According to LLC, AM diagnosis was established with the presence of at least 2 out of 3 of the following CMR features: oedema (with T2-weighted sequences), hyperaemia (with Early Gadolinium Enhancement–EGE) and necrosis or fibrosis (with Late Gadolinium Enhancement–LGE) .New LLC (nLLC) were recently published following the introduction of myocardial mapping and redefined imaging diagnosis according to the combined presence of a T1 criterion  and a T2 criterion  .According to the literature, the sensitivity of old Lake Louise Criteria (oLLC) varied with different clinical presentations (ranging from an 80% for the infarct-like onset to a 40% for the arrhythmogenic pattern ).To the best of our knowledge, the clinical performance of nLLC has not been tested yet in relation to different clinical presentations and in particular for atypical onsets. Our hypothesis was that parametric imaging could recognize subtle or diffuse forms of the disease, by quantitatively measuring T1 and T2 relaxation time variations.The purpose of our study was therefore to compare the diagnostic performance of old and new LLC among the different clinical patterns: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR).2); contrast media allergies; pregnancy or nursing; clinical history > 30 days  ml/m2 for IL and 76.1 [67.65–80.85] ml/m2 for AR, p < 0.05. EF was 33.9% [27.02–43.99%] for CM vs 56.04% [54.38–58.87%] for IL and 55.2% [49.78–60.10%] for AR, p < 0.05  normalized to Body Surface Area (BSA) and EF. EDV/BSA and EF are expressed as median and confidence interval (CI). EDV/BSA was 109.75 [89–121.15] ml/mInter-observer agreement was excellent for both oLLC and nLLC, resulting in a Cohen’s k of 0.94 and 0.98, respectively. In detail, the agreement was substantial for EGE ratio (k = 0.66) and excellent for LGE and edema assessment with T2w STIR (k was 0.94 and 0.90 respectively). As regards relaxometric images analysis, the agreement was almost perfect either for native T1 and for T2 mapping and for ECV . Doubtful cases were discussed until an agreement between the two operators was found.OLLC were able to diagnose acute myocarditis in 39 patients , vs 60 in nLLC , k = 0.57 [0.428–0.713], MNT p < 0.01.In particular, diagnosis of CM onset was detected in 5 patients 5/28, 17.9%) according to oLLC and in 17  with the nLLC . No statistical difference was found for AR onset, where oLLC were positive in 3 patients  and nLLC in seven of them , k = 0.49 [0.111–0.876], MNT p > 0.05 and for IL onset , 12 for CM  and 4 for AR presentation  , 24 with CM presentation  and 16 with IL pattern . According to EMB, acute myocarditis was present in 2 patients with AR onset , 22 patients with CM  and 6 patients with IL .Given the limited number of AR individuals, analysis was carried out by only comparing CM and IL presentation.Diagnostic Accuracy (DA) in IL onset was 75% 47.62%–92.73%] for both oLLC and nLLC; in CM presentation, DA was 41.7% [15.17%–72.33%] with oLLC and 66.7% [34.89%–90.08%] with nLLC. DA for all clinical patterns  was 52.3% [29.78%–74.29%] with oLLC and 71.4% [47.82%–88.72%] with nLLC  provides sufficient information to display typical inflammation features like oedema , necrosiAs a consequence, we found no added value from the use of relaxometry-based sequences which yielded to comparable results between oLLC vs nLLC, for diagnostic performances with a substantial degree of agreement [0.73 (0.543–0.912)] and a DA of 75% [47.62%–92.73%] for both Criteria using EMB as a reference standard.We also observed three cases of diffuse myocardial damage who were clinically categorized as fulminant myocarditis (FM). FM has been described as an acute disease due to a severe inflammatory response that requires mechanical or electrical support and the eventual management of threatening arrhythmias. Although a typical pattern of CMR myocardial damage could not be identified in this subgroup, oLLC well performed in those patients, showing an equal diagnostic performance as compared to nLLC. Our results are supported by the literature . In factCMR appearance of cardiomyopathic forms reflects the different evolution of myocardial damage which has been described as the result of a prolonged subacute inflammatory response  and myocLV dysfunction and clinical symptoms are usually preceded by viral persistence in myocardial tissue, which triggers the activation of autoimmune processes inducing subtle and diffuse myocardial damage . AccordiA similar potential mechanism has been hypothesized in arrhythmic disease onset, which pathogenesis still needs to be clarified. In some cases, arrhythmias originates from re-entrant mechanisms due to foci of fibrosis and extracellular matrix expansion that occur in the chronic phase of the infection . It has Main limitations of our study concerns the small sample size and, in particular, the low number of patients who underwent EMB. Moreover, biopsy was only performed in those subject whose CMR and clinical diagnosis was unclear: according to clinical guidelines EMB was used as a diagnostic tool only in patients with heart failure with or without LV dilation and/or new onset arrhythmias  (thus, mOur study has shown a significant added diagnostic value of nLLC in patients with CM forms of myocarditis, reflecting the superior detection of subtle/diffuse forms of myocardial involvement characterizing myocardial mapping imaging. Conventional sequences remain highly accurate in IL forms, as a consequence of the predominant active inflammatory manifestations associated with acute symptoms with troponin raise and typical ECG-changes. No significant advantages were found in the application of nLLC in patients with AR onsets. Pathological substrate triggering arrhythmias in myocarditis remains debated, but likely depends on a combination of direct viral infection and/or structural damage to the conduction system which is poorly depictable with CMR imaging. As an additional peculiarity, image quality is highly influenced by the presence of arrhythmias, further limiting accuracy of the method in this specific clinical setting.Larger prospective studies, also investigating on other imaging parameters such as myocardial strain, intra-cavitary fluid analysis or early myocardial T1 mapping , are exp