Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

BACKGROUND: Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. METHODS AND RESULTS: We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. CONCLUSIONS: Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis.

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

Myocarditis and sports in the young: data from a nationwide registry on myocarditis-"MYKKE-Sport".

Background: Myocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young. Patient: Every patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis. Method: This study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013-June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database. Results: 58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports. Conclusion: Sports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

SCMR expert consensus statement for cardiovascular magnetic resonance of acquired and non-structural pediatric heart disease.

Cardiovascular magnetic resonance (CMR) is widely used for diagnostic imaging in the pediatric population. In addition to structural congenital heart disease (CHD), for which published guidelines are available, CMR is also performed for non-structural pediatric heart disease, for which guidelines are not available. This article provides guidelines for the performance and reporting of CMR in the pediatric population for non-structural ("non-congenital") heart disease, including cardiomyopathies, myocarditis, Kawasaki disease and systemic vasculitides, cardiac tumors, pericardial disease, pulmonary hypertension, heart transplant, and aortopathies. Given important differences in disease pathophysiology and clinical manifestations as well as unique technical challenges related to body size, heart rate, and sedation needs, these guidelines focus on optimization of the CMR examination in infants and children compared to adults. Disease states are discussed, including the goals of CMR examination, disease-specific protocols, and limitations and pitfalls, as well as newer techniques that remain under development.

Compensatory Upregulation of Anti-Beta-Adrenergic Receptor Antibody Levels Might Prevent Heart Failure Presentation in Pediatric Myocarditis.

Background: Myocarditis can be associated with severe heart failure and is caused by different inflammatory and autoimmune responses. The aim of this study was to describe the immunological response in children with myocarditis by analyzing anti-beta-adrenergic receptor antibodies (anti-ß-AR Abs). Methods: Sera of children who were hospitalized with biopsy-proven myocarditis were prospectively collected between April 2017 and March 2019. Anti-ß1-AR Ab, anti-ß2-AR Ab, and anti-ß3-AR Ab were quantified by a CE-certified ELISA kit. According to normal values for immunoglobulin G (IgG), three age groups, <1, 1-5, and >5-17 years, were defined. Children without inflammatory cardiac pathology and no heart failure signs were served as a control group. Results: We compared 22 patients with biopsy-proven myocarditis and 28 controls. The median age (interquartile range) of the myocarditis group (MYC) was 12.1 (2.7-16.4) years, 13 men, left ventricular ejection fraction (LVEF) 51% and for control group, the median age was 5.0 (3.0-6.8) years, nine men, LVEF 64%. Myocarditis patients in the age group >5-17 years showed significantly higher anti-ß3-AR Ab levels as compared to controls (p = 0.014). Lower anti-ß2-AR Ab and anti-ß3-AR Ab levels were significantly correlated with higher left ventricular diameters in myocarditis patients. The event-free survival using a combined endpoint (mechanical circulatory support [MCS], transplantation, and/or death) was significantly lower in myocarditis patients with antibody levels below the median as compared to myocarditis patients with antibody levels ≥ the median. Conclusion: Anti-ß-AR Ab levels are increased in children with myocarditis and >5 years of age. These antibodies might be upregulated compensatory to prevent further cardiac deterioration. A worse event-free survival in patients with lower anti-ß-AR Ab levels might be a therapeutic target for immunoglobulin substitution.

Quantitative Ultrasound Assessment of Early Osteoarthritis in Human Articular Cartilage Using a High-Frequency Linear Array Transducer.

Quantitative ultrasound (QUS) assessment of osteoarthritis (OA) using high-frequency, research-grade single-element ultrasound systems has been reported. The objective of this ex vivo study was to assess the performance of QUS in detecting early OA using a high-frequency linear array transducer. Osteochondral plugs (n = 26) of human articular cartilage were scanned with ExactVu Micro-Ultrasound using an EV29L side-fire transducer. For comparison, the samples were also imaged with SAM200Ex, a custom 40-MHz scanning acoustic microscope with a single-element, focused transducer. Thirteen QUS parameters were derived from the ultrasound data. Magnetic resonance imaging (MRI) data, with T1 and T2 extracted as the quantitative parameters, were also acquired for comparison. Cartilage degeneration was graded from histology and correlated to all quantitative parameters. A maximum Spearman rank correlation coefficient (ρ) of 0.75 was achieved using a combination of ExactVu QUS parameters, while a maximum ρ of 0.62 was achieved using a combination of parameters from SAM200Ex. A maximum ρ of 0.75 was achieved using the T1 and T2 MRI parameters. This study illustrates the potential of a high-frequency linear array transducer to provide a convenient method for early OA screening with results comparable to those of research-grade single-element ultrasound and MRI.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Same same, but different? The neurological presentation of wildtype transthyretin (ATTRwt) amyloidosis.

BACKGROUND: Both hereditary transthyretin (ATTRv) amyloidosis and wildtype transthyretin (ATTRwt) amyloidosis can be associated with neurological diseases such as carpal tunnel syndrome and polyneuropathy. While ATTRv amyloidosis has been extensively studied, to date little is known about neurological complications of ATTRwt amyloidosis. In particular, the prevalence, pattern and extent of polyneuropathy and autonomic dysfunction has not been adequately investigated in the context of ATTRwt amyloidosis. To tackle this issue, we aimed to characterise the neurological presentation of ATTRwt amyloidosis and to compare between the presentations of ATTRv and ATTRwt amyloidoses. PATIENTS AND METHODS: Between November 2019 and September 2020, we included 50 patients with ATTRwt amyloidosis in this cohort study. All patients presented to the amyloidosis centre in Berlin, Germany and underwent neurological, cardiological and radiological work-up including neurological examination, laboratory testing, nerve conduction studies (NCS), echocardiography and scintigraphy. Patients were screened for symptoms of autonomic dysregulation and a subgroup of patients underwent tilt-table testing for orthostatic dysregulation. RESULTS: The cohort included 46 men and 4 women; the mean age of the study participants was 80.6 (standard deviation [SD] ± 5.0) years. All patients showed signs of cardiomyopathy on echocardiography. Neurological examination revealed peripheral, symmetric and length-depended predominately sensory polyneuropathy in 74% (n = 37) of patients. Neuropathy impairment scores (NIS) ranged from 0 to 50 with an average score of 8.4 (SD ± 10.1) indicating mild to moderate impairment. 90% and 92% of patients were classified as FAP stage I and PND stage I, respectively. Unilateral or bilateral carpal tunnel syndrome (CTS) was present in 70% (n = 35) and spinal stenosis was seen in 11% (n = 5) of patients. We detected a low rate of autonomic symptoms with a median COMPASS-31 total score of 18.4 points (IQR 32.4 points). Additional tilt-table testing of a subgroup of 8 patients yielded negative results for orthostatic intolerance. CONCLUSION: Distal-symmetric, predominantly sensory polyneuropathy is a common neurological complication in ATTRwt amyloidosis besides carpal tunnel syndrome and spinal stenosis, further substantiating the systemic character of the disease. Compared to ATTRv amyloidosis, the severity of polyneuropathy in ATTRwt amyloidosis is milder and without relevant motor involvement. Symptoms of autonomic dysfunction were not common in this cohort. Nevertheless, ATTRwt amyloidosis is a treatable disease and should be included in the differential diagnosis of sensory polyneuropathy in the elderly.

An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

BACKGROUND: In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°). METHODS: In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i. RESULTS: In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence. CONCLUSIONS: Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

Pathogenic Variants Associated With Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis.

BACKGROUND: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. METHODS: A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM). RESULTS: Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years; P<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM (BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2, and TTN). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals (P=0.0003). Event-free survival was lower (P=0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM. CONCLUSIONS: We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group-specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

Sex-Specific Differences of the Inflammatory State in Experimental Autoimmune Myocarditis.

Increasing evidence suggests male sex as a potential risk factor for a higher incidence of cardiac fibrosis, stronger cardiac inflammation, and dilated cardiomyopathy (DCM) in human myocarditis. Chronic activation of the immune response in myocarditis may trigger autoimmunity. The experimental autoimmune myocarditis (EAM) model has been well established for the study of autoimmune myocarditis, however the role of sex in this pathology has not been fully explored. In this study, we investigated sex differences in the inflammatory response in the EAM model. We analyzed the cardiac function, as well as the inflammatory stage and fibrosis formation in the heart of EAM male and female rats. 21 days after induction of EAM, male EAM rats showed a decreased ejection fraction, stroke volume and cardiac output, while females did not. A significantly elevated number of infiltrates was detected in myocardium in both sexes, indicating the activation of macrophages following EAM induction. The level of anti-inflammatory macrophages (CD68+ ArgI+) was only significantly increased in female hearts. The expression of Col3A1 and fibrosis formation were more prominent in males. Furthermore, prominent pro-inflammatory factors were increased only in male rats. These findings indicate sex-specific alterations in the inflammatory stage of EAM, with a pro-inflammatory phenotype appearing in males and an anti-inflammatory phenotype in females, which both significantly affect cardiac function in autoimmune myocarditis.

Outcome of medical therapy, repeat intervention, and mitral valve surgery after failed MitraClip therapy.

OBJECTIVES: Optimal treatment for residual mitral regurgitation (MR) after MitraClip failure is not clearly defined. We report our clinical experience and discuss treatment options. METHODS: Between January 2013 and January 2018, 37 patients (75 ± 8.9 years, 46% male) were admitted for symptomatic MR (grade 3.1 ± 0.47) diagnosed after previous MitraClip therapy. Clinical outcome of these patients, who underwent medical therapy alone (n = 8, M-group), repeat MitraClip therapy (n = 8, reMC group), or mitral valve surgery (n = 21, S-group) for residual MR, were retrospectively analyzed. RESULTS: Thirty-day survival was 88% (M-group), 100% (reMC-group), and 76% (S-group). The rate of discharge to home was 88% in the reMC-group, better than 38% in the M-group (p = 0.051) and 19% in the S-group (p < 0.001). Perioperative non-survivors in the S-group had high surgical risk with median logistic EuroSCORE of 64.6% (interquartile range 57.4%-87.0%); all died from low cardiac output syndrome or multiple organ failure. The main MR pathologies resulted from leaflet tear and tethering in the M-group, tethering in the reMC-group, and degenerative valve and leaflet tear in the S-group. Kaplan-Meier analysis of overall survival at 1 year showed better outcome for patients in the reMC-group (50%, 95% CI 15.2-77.5%) and S-group (47.6%, 95% CI 25.7-66.7%), as compared to those in the M-group (12.5%, 95% CI 0.70-42.3%) (log-rank test p = 0.108 and p = 0.167, respectively). CONCLUSION: Medical therapy alone after failed MitraClip therapy resulted in poor 1-year prognosis. In patients without extremely high surgical risk, repeat MitraClip therapy, or surgical revision MIGHT BE CONSIDERED depending on valve pathology and cardiac comorbidities.

Isolated atrial amyloidosis suspected by electrophysiological voltage mapping and diagnosed by 99m Tc-DPD scintigraphy.

We present not-yet-seen multimodal images of a 55-year-old female patient with isolated atrial amyloidosis (IAA) who clinically suffered from multiple atrial arrhythmias and heart failure symptoms with preserved left ventricular ejection fraction. We aim to show structural and functional abnormalities detected by electrophysiological voltage mapping, cardiac magnetic resonance imaging (MRI) [cMRI; atrial strain measurements, late gadolinium enhancement (LGE) visualization], and 99m Tc-DPD scintigraphy. Bipolar voltage mapping performed during two electrophysiological procedures showed diffuse left atrial low-voltage areas (bipolar < 0.5 mV) and also a moderately diseased right atrium suspected of infiltrative cardiomyopathy. Catheter ablation did successfully treat a left atrial and two right atrial focal tachycardias. For further diagnostics, a 3T cMRI was performed, revealing a subendocardial circumferential left atrial LGE and pathological atrial strain measurements, especially during conduit and reservoir phase. Afterwards, nuclear imaging with 559 MBq of 99m Tc-DPD was performed. The scan revealed amyloid infiltration of the left atrium. Neither an uptake in the ventricular myocardium nor an extra-cardiac uptake of DPD was seen. Genetic testing for transthyretin amyloidosis mutations in this patient was negative, and peripheral neuropathy was ruled out by electromyogram analysis. The synopsis of these findings reveals IAA as the most possible diagnosis and showed isolated atrial nuclear tracer uptake with 99m Tc-DPD scintigraphy for the first time. Non-invasive imaging techniques might help in suggesting IAA but need further investigation.

Outcome comparison of mitral valve surgery and MitraClip therapy in patients with severely reduced left ventricular dysfunction.

AIMS: The aim of this study was to compare the outcomes of surgical mitral valve repair or replacement (sMVR) and percutaneous edge-to-edge repair using MitraClip (pMVR) in patients with severe left ventricular dysfunction affected by functional mitral regurgitation (FMR). METHODS AND RESULTS: We retrospectively identified 132 patients with left ventricular ejection fraction (LVEF) â‰¦ 30% submitted to sMVR (n = 47) or pMVR (n = 85) for FMR at our centre from January 2013 to December 2017. To adjust for baseline imbalances, we used a propensity score matching by age, logistic EuroSCORE, and left ventricular end-systolic volume. After being matched, MitraClip therapy showed lower perioperative mortality and rate of complications yet increased residual mitral regurgitation (MR) grade than did surgery (0.2 ± 0.50 in sMVR vs. 1.3 ± 0.88 in pMVR, P < 0.0001). According to stratified multivariate Cox model analysis, residual MR severity was an independent risk factor for cardiac death [hazard ratio (HR), 2.81; 95% confidence interval [CI], 1.44-5.48, P = 0.0025] and re-hospitalization for heart failure (HR, 3.07; 95% CI, 1.50-6.29, P = 0.0022) at 1 year follow-up. Stratified multivariable Cox regression analysis at 3 years identified pMVR as risk factor for cardiac death (HR, 0.19; 95% CI, 0.040-0.86, P = 0.031) and re-hospitalization for heart failure (HR, 0.28; 95% CI, 0.077-0.99, P = 0.048). CONCLUSIONS: In patients with FMR and LVEF ≤ 30%, MitraClip therapy resulted in lower perioperative complications and mortality than sMVR. However, surgically treated patients who survived the perioperative stage had less residual MR and experienced lower rates of re-hospitalization for heart failure at 1 year and lower cardiac mortality at 1 and 3 years of follow-up than did patients undergoing pMVR.

Impact of preinterventional tricuspid regurgitation on outcome of MitraClip therapy in patients with severely reduced ejection fraction.

Aim: To evaluate the impact of preinterventional moderate-to-severe functional tricuspid regurgitation (FTR) on early outcome after percutaneous edge-to-edge mitral valve repair (pMVR) with MitraClip procedures for functional mitral regurgitation (FMR) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results: From January 2013 to December 2017, 80 patients with HFrEF (ejection fraction 22%±5.3%) and FMR (grade 3.0±0.36) underwent successful pMVR. The 3-year actuarial survival was 58%. However, 73% (n=22) of non-survivors died of cardiac failure within 1 year. Patients were categorised into none-to-mild (n=36) and moderate-to-severe (n=44) postinterventional FTR groups according to pre-MitraClip tricuspid regurgitation grade. Cox regression analysis on 1-year survival demonstrated an impact of FTR severity (HR=1.8, 95% CI 1.01% to 3.09%, p=0.047), preoperative New York Heart Association class (HR=2.8, 95% CI 1.2% to 6.5%, p=0.015) and peripheral artery disease (HR=5.4, 95% CI 1.6 to 18, p=0.0054). Kaplan-Meier analysis showed that 1-year cardiac death was higher in the moderate-to-severe FTR group (p=0.048). In our study, 77% of pre-MitraClip moderate-to-severe FTR cannot be significantly reduced. Post-MitraClip moderate-to-severe FTR grade was related to lower survival (p<0.001). Conclusion: In patients with HFrEF treated with MitraClip for FMR, moderate-to-severe FTR was an independent predictor of cardiac death within 1 year. To improve survival, additional therapy to residual FTR should be considered in early phase after MitraClip therapy.

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: Normal behavior and validation in patients with amyloidosis.

BACKGROUND: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms. METHODS: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13). RESULTS: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength. CONCLUSIONS: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms.

First paediatric cohort for the evaluation of inflammation in endomyocardial biopsies derived from congenital heart surgery.

BACKGROUND: Endomyocardial biopsies (EMB) are the gold standard for the diagnosis of myocarditis in children and adults. The existing WHO/ISFC criteria for lymphocytic cell infiltrates by are based on the myocardium of adults. The aim of this study was to present a paediatric control cohort for the evaluation of inflammation in EMB of children. METHODS: In this study endomyocardial tissue from 62 children under 4 years of age was investigated, being collected during a planned open heart surgery with routine resection from ventricular site. Patients had no history of infection or myocardial inflammation. The heart tissue was formalin fixed and embedded in paraffin. Four µm thick tissue sections were stained with haematoxylin and eosin, Masson's trichrome, and Giemsa. Immunohistochemical stainings included quantitative evaluation of CD3+ T cells, CD20+ B cells, CD68+ macrophages and MHCII expression. RESULTS: The myocardium was obtained in 96.8% (n = 60) of the cases from the right and in 3.2% (n = 2) from the left ventricle. The median age (interquartile range) at biopsy was 0.5 years (0.3-0.9), 66.1% male. Within this cohort, a median of 2.5/mm2 (1.0-4.0) CD3+ T cells, 0.5/mm2 (0.0-0.6) CD20+ B cells and 4.0/mm2 (2.5-6.0) CD68+ macrophages were detected. The MHC II grade was 0 in 71.0% (n = 44) and 1 in 29.0% (n = 18). CONCLUSION: This is the first paediatric control cohort being relevant for the correct interpretation of inflammatory heart diseases in EMB. The lymphocytic cell numbers in children needing congenital heart surgery without myocardial inflammation are below the existing values in adults.

Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Myocardial T1 maps reflect histological findings in acute and chronic stages of myocarditis in a rat model.

BACKGROUND: Cardiovascular magnetic resonance offers both diagnostic and prognostic information in myocarditis. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, in the acute and in the chronic phases of the disease and to compare its course with histological and immunohistochemistry findings. METHODS: Male young Lewis rats were immunized with 0.25 mg porcine myocardial myosin into the rear footpads on day 0. Native and contrast-enhanced ECG-triggered cardiac MRI examinations were performed before immunization on day 0 and on days 14, 21 and 35. Left ventricular function, pre- and post- contrast T1 parameters and LGE images were assessed using Small animal look-locker inversion recovery (SALLI). For each of the indicated time points a minimum of 4 rats were randomly sacrificed for pathological investigations including conventional histology (HE and Sirius-Red staining) and immunohistochemistry (CD 68) investigations. RESULTS: All immunized rats developed myocarditis (morbidity 100%). Histologically we observed increased wall thickness with biventricular macrophage-rich mixed inflammatory infiltrates. All rats with a histologically severe myocarditis showed increased native T1 and decreased post-contrast T1 of the myocardium. CONCLUSIONS: The assessment of native T1 and post-contrast T1 allows accurate differentiation between healthy myocardium and myocardium with inflammation and also between the acute and chronic phases of the disease.