Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is an increasingly recognized disease in elderly individuals. We aimed to perform a cross-sectional survey investigating the current diagnostic journey of ATTRwt patients in the Czech Republic from initial symptoms to final diagnosis. Between November 2022 and May 2023, most data were prospectively obtained using a dedicated questionnaire from 118 ATTRwt-CA patients during the regular outpatient consultation. The rest of the data were taken by attending physicians from medical records. The mean age of the patients at the time of diagnosis was 77 ± 6 years, 85.6

BACKGROUND:No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS:In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS:Median age at presentation was 48 years (first to third quartile, 34-59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%-48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis-associated form (13.1%) at 3 years (P=0.15). CONCLUSIONS:Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06447935.

BACKGROUND AND AIM OF THE STUDY: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is an increasingly recognized disease in elderly individuals. We aimed to perform a cross-sectional survey investigating the current diagnostic journey of ATTRwt patients in the Czech Republic from initial symptoms to final diagnosis. METHODS: Between November 2022 and May 2023, most data were prospectively obtained using a dedicated questionnaire from 118 ATTRwt-CA patients during the regular outpatient consultation. The rest of the data were taken by attending physicians from medical records. RESULTS: The mean age of the patients at the time of diagnosis was 77 ± 6 years, 85.6% were males. The time interval from the onset of clinical scenario leading to suspicion of CA to suspected diagnosis was 14±24 months, while the subsequent period to definite ATTRwt-CA diagnosis was 2.5±2.3 months. Heart failure primarily led to the suspicion of CA in 61.9%, followed by suspicious echocardiographic findings (12.7%) and atrial fibrillation or flutter (6.8%). The history of carpal tunnel syndrome was the most common extracardiac manifestation found in 53.9% subjects, with median duration of 99 months. The diagnosis of CA was most often first suspected by outpatient cardiologists (33.1%) and cardiologists working at a cardiocenter (25.4%). At the time of diagnosis, NYHA class I or II was present in 10% and 56% of patients, respectively. The definite ATTRwt-CA diagnosis was made noninvasively in 63% cases. CONCLUSIONS: A relatively long-time delay still exists between the onset of clinical manifestations and suspicion of CA. Nevertheless, once CA is suspected, the definite ATTRwt-CA diagnosis is made early. Although heart failure still represents the most common clinical scenario, several other clinical profiles lead quite frequently to suspicion of the disease. The non-invasive diagnostics of ATTRwt-CA is done in majority of our patients, who are diagnosed mostly in early stages of the disease. The awareness of ATTRwt manifestations must be increased in order to shorten the whole diagnostic process of the disease.

Cardiac involvement in light chain amyloidosis (AL-CA) represents an infiltrative heart disease. The aim of the study was to recognize differences between patients suffering from light chain amyloidosis with and without cardiac involvement in 12-lead electrocardiography (ECG) and 24-h Holter ECG monitoring. We prospectively analyzed data in 39 (median 66 [IQR 62;71] years, 62

Wild-type transthyretin cardiac amyloidosis (ATTRwt CA) is increasingly recognized as an important cause of heart failure and arrhythmias in older people. There are several clinical, echocardiographic, electrocardiographic (ECG) and laboratory features that increase the suspicion for ATTRwt CA. Presentation and phenotype can, however, be associated with atypical findings making it difficult to make a correct diagnosis. A 65-year-old man was admitted for an acute coronary syndrome. Echocardiography revealed diffuse concentric left ventricular (LV) thickening. Because of a history of bilateral carpal tunnel syndrome and polyneuropathy, the patient underwent dedicated laboratory testing and diphosphonate scintigraphy the results of which were suggestive of transthyretin cardiac amyloidosis. Also, a dynamic LV outflow tract obstruction due to the systolic anterior motion of the anterior mitral valve was noted on echocardiography during the initial investigations. Genetic testing for hypertrophic cardiomyopathy was negative. Seeking a conclusive diagnosis, endomyocardial biopsy was performed. This confirmed the diagnosis of ATTRwt CA. The presence of dynamic LV outflow tract obstruction is typically seen in patients with sarcomeric hypertrophic cardiomyopathy. It can be rarely seen also in individuals with cardiac amyloidosis, including ATTR-wt CA. The presence of so-called red flags in patients’ history, physical examination, laboratory test, ECG and imaging should raise suspicion for other etiologies of LV wall thickening than hypertrophic cardiomyopathy. Although noninvasive diagnosis of ATTRwt CA is possible in most patients, endomyocardial biopsy remains necessary in cases with diagnostic ambiguity.

AbstractAimsRecent‐onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype–phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes.Methods and resultsIn this prospective study, a total of 386 Czech RODCM patients with symptom duration ≤6 months underwent genetic counselling and whole‐exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy‐related genes was correlated with the occurrence of all‐cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to >50% or ≥10% absolute increase, with a left ventricular end‐diastolic diameter ≤33 mm/m2 or ≥10% relative decrease. Median follow‐up was 41 months. RODCM was familial in 98 (25%) individuals. Class 4–5 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin‐truncating variant (TTNtv) and 56 (14%) having non‐titin (non‐TTN) VOIs. The presence of class 4–5 non‐TTN VOIs, but not of TTNtv, heralded a lower probability of 12‐month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life‐threatening ventricular arrhythmias. Detection of class 4–5 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life‐threatening ventricular arrhythmias after 12 months. Class 4–5 VOIs of genes coding cytoskeleton were associated with an increased risk of life‐threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12 months and at the final follow‐up.ConclusionsRODCM patients harbouring class 4–5 non‐TTN VOIs are at higher risk of progressive heart failure and life‐threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.

Cardiomyopathies encompass a diverse group of diseases requiring specialized diagnostic and therapeutic approaches. Unlike more common conditions, some rarer forms demand advanced expertise and access to modern imaging and diagnostic tools. Recently, targeted treatments for diseases like obstructive hypertrophic cardiomyopathy, cardiac amyloidosis, Fabry, and Pompe disease have emerged. These therapies are often high-cost, subject to strict indications, and necessitate intensive patient monitoring. Given the complexity, diagnosis and treatment should be centralized in expert centers with adequate resources and coordination with healthcare payers to ensure an access to these treatments. This document, prepared by the Working Group on Myocardial and Pericardial Diseases of the Czech Society of Cardiology, outlines expert consensus on the necessary infrastructure for specialized cardiomyopathy units, which are expected to offer comprehensive care, including innovative and regulated therapies.

Abstract Aims In patients with recently diagnosed non‐ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short‐term follow‐up. The aim of our study was to assess the long‐term clinical course and stability of LVRR in these patients. Methods and results We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow‐up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end‐diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5‐year follow‐up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007–1.196), logBNP level (OR 2.02, CI 1.14–3.56), and PR interval (OR 1.02, CI 1.006–1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow‐up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end‐diastolic volume index (OR 0.97, CI 0.946–0.988), LVEF (OR 0.89, CI 0.83–0.96), and diastolic blood pressure (OR 1.04, CI 1.01–1.08) (P < 0.05 for all). Conclusions LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5‐year follow‐up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long‐term follow‐up.

European Journal of Heart FailureEarly View Invited Editorial Tailored immunosuppression in biopsy-proven immune-mediated myocarditis Petr Kuchynka, Corresponding Author Petr Kuchynka [email protected] 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic Corresponding author. 2nd Department of Medicine, Department of Cardiovascular Medicine, General University Hospital in Prague, First Faculty of Medicine, Charles University in Prague, U Nemocnice 2, 12808 Prague, Czech Republic. Tel: + 420 224 962634, Fax: + 420 224 912154, Email: [email protected]Search for more papers by this authorJan Krejci, Jan Krejci Department of Cardiovascular Diseases, St. Anne's University Hospital and Masaryk University Brno, Brno, Czech RepublicSearch for more papers by this authorTomas Palecek, Tomas Palecek 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech RepublicSearch for more papers by this author Petr Kuchynka, Corresponding Author Petr Kuchynka [email protected] 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic Corresponding author. 2nd Department of Medicine, Department of Cardiovascular Medicine, General University Hospital in Prague, First Faculty of Medicine, Charles University in Prague, U Nemocnice 2, 12808 Prague, Czech Republic. Tel: + 420 224 962634, Fax: + 420 224 912154, Email: [email protected]Search for more papers by this authorJan Krejci, Jan Krejci Department of Cardiovascular Diseases, St. Anne's University Hospital and Masaryk University Brno, Brno, Czech RepublicSearch for more papers by this authorTomas Palecek, Tomas Palecek 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech RepublicSearch for more papers by this author First published: 03 May 2024 https://doi.org/10.1002/ejhf.3276 The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. doi: 10.1002/ejhf.3220. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, et al. Management of acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document. Circ Heart Fail 2020; 13:e007405. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007405 10.1161/CIRCHEARTFAILURE.120.007405 PubMedWeb of Science®Google Scholar 2Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al.; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013; 34: 2636–2648. https://doi.org/10.1093/eurheartj/eht210 10.1093/eurheartj/eht210 PubMedWeb of Science®Google Scholar 3Seferović PM, Tsutsui H, McNamara DM, Ristić AD, Basso C, Bozkurt B, et al. Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy. 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Immunosuppressive therapy and risk stratification of patients with myocarditis presenting with ventricular arrhythmias. JACC Clin Electrophysiol 2020; 6: 1221–1234. https://doi.org/10.1016/j.jacep.2020.05.013 10.1016/j.jacep.2020.05.013 PubMedGoogle Scholar 10Caforio ALP, Giordani AS, Baritussio A, Marcolongo D, Vicenzetto C, Tarantini G, et al. Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study. Eur J Heart Fail. https://doi.org/10.1002/ejhf.3220 Published online ahead of print 17/04/24. 10.1002/ejhf.3220 Web of Science®Google Scholar 11Kuchynka P, Palecek T, Grus T, Schramlova J, Krsek D, Vitkova I, et al. A high frequency of viral agents yet absence of Borrelia burgdorferi is seen within the myocardium of subjects with normal left ventricular systolic function: An electron microscopy study. 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Acute myocarditis affects around 4–14 people per 100 000 each year globally. Approximately 2% to 9% of patients have haemodynamic instability and require inotropic agents or mechanical circulatory support (MCS) devices to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days.1 This case study underscores the key decision points, considerations, and advantages of combining both Impella and veno-arterial extracorporeal membrane oxygenation (VA ECMO) in the treatment of patients suffering from advanced stages of cardiogenic shock (CS) due to fulminant myocarditis. A 22-year-old male was admitted to the intensive care unit due to sustained ventricular tachycardia (VT). He experienced fatigue for the past 3 days, and on the night of admission, he reported palpitations and dyspnoea. The patient had a fever on the first day of hospitalization, which he suffered from for 3 days, with a high of 39.1°C. He also vomited for the first two nights. The initial ECG obtained from the ambulance revealed sustained VT (Figure 1A). Upon admission, the subsequent ECG displayed sinus rhythm, into which he spontaneously converted during transport; pathological ST elevations were seen in leads I, aVL, and V1–V5, and deep Q waves were noted in leads V1-V3 (Figure 1B). Despite these manifestations, vital signs upon admission were a blood pressure of 93/53 mmHg, a pulse rate of 101 beats per minute, and a lactate level of 1.9 mmol/L. He was free of symptoms during the initial assessment. The patient was diagnosed with Addison's disease, autoimmune hypothyroidism, and heart failure with a mildly reduced left ventricle ejection fraction (LVEF) of 45% in 2020. The treatment included prednisone, levothyroxine, ramipril, and bisoprolol. Cardiac magnetic resonance (CMR) 3 months after the treatment initiation showed normal left ventricular (LV) function without the presence of late gadolinium enhancement (LGE), and the temporary LV dysfunction was attributed to an endocrine disorder. Ramipril and bisoprolol were discontinued after the improvement of LVEF, and the patient continued to use levothyroxine and prednisone. Since then, the heart function has been assessed as normal with the use of echocardiography during regular check-ups with his cardiologist. The echocardiography performed on admission revealed significant reduction of LVEF (28%) due to severe global hypokinesis (Video S1). The right ventricle (RV) was of normal size with decreased systolic function [tricuspid annular plane systolic excursion (TAPSE) 14 mm and 9 cm s′ tissue Doppler imaging (TDI) of tricuspid annulus]. The initial value of highly sensitive troponin I was 18 752 ng/L with a peak value of 27 157 ng/L on the next day. The NT-proBNP level was 10 125 ng/L, and the peak lactate was 3.9 mmol/L. Selective coronary angiography was normal (Video S2A and Video S2B). On the second day, the patient developed signs of low cardiac output syndrome. Urgent CMR was performed, which revealed several non-contiguous midmyocardial LGE within the interventricular septum and LV free walls suggesting non-ischaemic damage of the LV myocardium (Video S3, Figure 2A). All laboratory tests on possible viral agents (including hepatitis and HIV) came back negative. For the suspected Addisonian crisis, we administered corticosteroids from the first day, starting with a bolus of 100 mg of hydrocortisone followed by 200 mg administered daily in four doses.2 On the second morning, the patient received inotropic support due to low cardiac output syndrome (ScV02 36.9%, VTI [velocity time integral] LVOT 8 cm) using levosimendan. In the evening, the patient experienced recurrent episodes of sustained VT with four defibrillations; intravenous amiodarone was administered to prevent VT recurrence. After this episode, his echocardiography showed progressively worsening LV dysfunction with an LVEF of 10%, and the patient experienced severe pulmonary oedema, which required treatment with non-invasive ventilation support (FiO2 100%). A rapid shock-team call was made, and the decision was to initiate Impella CP Smart support, inserted through the right femoral artery with an initial flow of 3.2 L/min (P8), which led to rapid regression of pulmonary oedema, lactate normalization, and restoration of urine output. Since the Impella implantation, the patient has been free from any arrhythmias. However, on the morning of the next day, the persistence of severely reduced LV systolic function, together with worsened RV function (TAPSE 12 mm) and high haemolysis (serum free haemoglobin 3058.5 mg/L) on Impella support, led to the decision to start awake veno-arterial extracorporeal membrane oxygenation (Maquet Cardiohelp, 19F arterial cannula, 23F vein cannula) with a flow of 4.2 L/min. The Impella flow was then lowered to 1.2 L (P2) as an active LV unloading strategy. This approach resolved the problem of haemolysis (the serum free haemoglobin was 79.8 mg/L the next day). Immediately after the ECMO implantation, an EMB was performed with preliminary results suggestive of acute necrotizing lymphocytic myocarditis (Figure 3). Based on the EMB results, treatment with high pulses of corticosteroids was started on the same day (a pulse of 1 g of methylprednisolone on the first day, followed by a dose of 100 mg of methylprednisolone on the second day, then reducing the dose to 80 mg a day for the next 7 days) along with high-dose intravenous immunoglobulins (1 mg/kg in total, divided into 3 doses given over 3 days). After starting with higher doses of corticosteroids for 7 days, the patient was switched to hydrocortisone at 200 mg per day due to ongoing stressful circumstances requiring substitution. After another 7 days, the dosage was reduced to prednisone at 20 mg per day. Fludrocortisone at a dosage of 0.1 mg per day was added later, and the dosage was gradually reduced over the following months with the endocrinologist's guidance. The patient was on ECMO and Impella for 5 days with minimal LV pulsatility (Figure 4). On day 6, he began to show the primary signs of significant RV recovery, and over the next few days, we observed further gradual improvement in both LV and RV function. This enabled us to slowly wean off ECMO, with successful fully percutaneous explantation of both the Impella and ECMO on the 8th and 9th days post-implantation, respectively (Figure 5).Details of the laboratory results are presented in Figure 6. This case study has several important implications. First, it describes the key steps of the diagnostic and decision-making process in fulminant myocarditis. Second, it underscores the advantages of combining both Impella and ECMO, often referred to as ECPELLA or ECMELLA, in the treatment of patients suffering from advanced stages of CS due to fulminant myocarditis. Given the limited availability of data concerning the management of fulminant myocarditis with CS, we posit that this case report has the potential to illuminate the importance of early initiation of left ventricular (LV) unloading and combined support in cases with deteriorating CS. Both the European Society of Cardiology (ESC)3 and the American Heart Association (AHA)4 currently advise the use of MCS in cases of acute myocarditis complicated by refractory heart failure or CS.5 Fulminant myocarditis often proves to be reversible, making the temporary utilization of short-term MCS devices an appealing therapeutic strategy. An analysis of myocarditis management trends in the United States from 2005 to 2014 revealed an increasing rate of temporary MCS utilization, growing from 4.5% to 8.6%.6 V-A ECMO remains the most widely employed MCS in fulminant myocarditis complicated by refractory CS.7 V-A ECMO provides robust circulatory support at the expense of elevated LV afterload and considerable risks of bleeding, vascular, and ischaemic complications. That's why we opted for the Impella CP Smart device implantation due to its advantages over ECMO and other MCS. Notably, Impella actively unloads the LV, favouring myocardial recovery and improvement in pulmonary oedema compared with VA-ECMO. Direct LV unloading, reduced mechanical workload, lowered myocardial oxygen demand, decreased wall stress, and improved subendocardial coronary blood flow may explain the immediate effect of device insertion on the disappearance of VT in our patient. However, all MCS devices have inherent limitations and potential complications. Impella CP provides limited LV support, and high pump flows may lead to significant haemolysis. Given the high haemolysis, worsened RV function, and expected recovery timeline spanning days to weeks, we selected peripheral percutaneous V-A ECMO. This choice enabled us to decrease Impella flow and ensure complete biventricular circulatory and respiratory support until the appearance of cardiac recovery. There are also other possible MCS combinations; one of the most deployed is the use of an intra-aortic balloon pump (IABP) with VA ECMO. However, the IABP provides only passive and limited LV support, which may not be sufficient in severe CS cases. Additionally, a recently published retrospective registry study from Japan revealed that a substantial proportion of patients with myocarditis complicated by CS can be managed by Impella alone without VA ECMO, and the survival rate for the Impella standalone group in this study was high (83.2%).8 Despite the lack of prospective and randomized data, there are experimental and clinical studies showing better efficacy of ECPELLA compared with the IABP combination with VA ECMO, although at the expense of higher complication rates with Impella compared with IABP.9 The survival advantage of ECPELLA over those solely treated with VA ECMO has been highlighted in various observational studies.10 However, contrasting these encouraging findings, a case series from a high-volume centre in Hannover, Germany, involving seven patients with influenza-associated myocarditis supported by ECPELLA, indicated a zero survival rate.11 Considering the variability in myocarditis presentation and severity, gathering robust evidence remains challenging. To achieve optimal outcomes, we recommend a comprehensive case assessment, shock-team deliberation, and decision-making involving strategies for haemodynamic deterioration. Tailoring the indication and timing of MCS devices to individual patients is essential, dependent on numerous factors outlined in Figure 7. Emphasis should be placed on LV unloading, rapid diagnosis, and treatment. Furthermore, it is important to note that the combination of ECMO and Impella is associated with elevated complication rates, primarily bleeding and vascular complications.12 To mitigate these issues, comprehensive strategies, including ultrasound and X-ray guided procedures and MCS insertions, fully percutaneous closure techniques, and intensive monitoring of bleeding, coagulation, and haemolysis, should be employed. Additionally, the patient was kept awake throughout the course of hospitalization, and the respiratory failure in this case was effectively managed by non-invasive ventilation and early Impella CP. The awake MCS strategy is used for most CS patients in our hospital. In a retrospective observational study from Paris, the awake ECMO group had significantly lower rates of pneumonia, tracheostomy, renal replacement therapy, less antibiotic and sedative consumption, and even reduced short-term and long-term mortality compared with ventilated patients.13 This study confirms previous reports suggesting that an awake approach to patients treated with MCS is feasible and effective for a significant proportion of patients with CS. The patient was discharged with an LVEF of 58%. After an 8-week follow-up, the patient was free of symptoms, and his LV function was 57% (Video S4). The CMR performed 8 weeks after discharge from the hospital showed no signs of LGE (Figure 2B). At the 6-month follow-up, the patient was still free of symptoms with normal LVEF. In conclusion, the combined use of Impella and ECMO holds potential for reversing the lethal course of refractory CS due to fulminant myocarditis. Success hinges on appropriate patient selection, timing of implantation, active LV unloading, and mitigation of potential complications associated with MCS. In this case, early Impella and VA ECMO implantation proved pivotal in reversing cardiogenic shock and facilitating successful bridge-to-cardiac recovery. Decisions regarding device selection and timing should be tailored to individual patients and coordinated within an experienced shock team. This study was supported by MH CZ-DRO-VFN64165 VFN: General University Hospital in Prague and the Charles University Research Program Cooperation – Intensive Care Medicine. Daniel Rob received consulting honoraria from Abiomed. Jan Belohlavek received consulting honoraria from Abiomed, Getinge, Resuscitec and Xenios. Michaela Zemkova, Milan Dusik, Jan Pudil, Tomas Palecek and Ivana Vitkova declare that they have no conflict of interest. Video S1. The initial echocardiography – apical four chamber projection. The initial echocardiography revealed significant reduction of ejection fraction (28%) of left ventricle with severe global hypokinesis with slightly better kinesis of the basal parts of left ventricle. Video S2A. Selective coronary angiography. Selective coronary angiography showed coronary arteries without any stenosis. A) right coronary artery. Video S2B. Left coronary artery, left anterior descending artery and left circumflex artery. Video S3. CMR. This video from cardiac magnetic resonance shows reduced ejection fraction of the left ventricle (around 30%), akinesis of the apex and apical halves of anterior and lateral wall of LV and anterior part of interventricular septum. Video S4. Transthoracic echocardiography during follow-up after eight weeks – apical four chamber projection. The echocardiography shows no kinetics disorders of the LV, and its ejection fraction is 57% according to Simpson. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract Aims Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. Methods and results 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = −0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = −0.38, P < 0.001) or 3D LVEF (r = −0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75–0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). Conclusion 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.

BACKGROUNDTransthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin.METHODSIn this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months.RESULTSA total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group.CONCLUSIONSIn this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

Abstract Funding Acknowledgements Type of funding sources: None. Aim Cardiac amyloidosis (CA) reflects an infiltrative heart disease with poor prognosis. Aim of the study was to recognise differences between patients with and without CA in 12-lead electrocardiography (ECG) and 24hr Holter ECG monitoring and identify dependence of ECG and Holter ECG monitors on disease progression. Methods We prospectively analyzed clinical profile, echocardiographical pattern, ECG and 24hr Holter monitoring in 39 (66 (62; 71) years, 62% males) consecutive patients with AL amyloidosis screened to cardiac involvement. Results Out of all patients, CA was confirmed in 26 (67%) patients. All patients with cardiac AL amyloidosis manifested at least one pathology on ECG, what was contrast to low prevalence in patients without cardiac involvement (54%), p < 0.001. Abnormal Holter ECG was seen in 77 % and 62 % of patients with and without cardiac involvement, respectively. Patients with cardiac involvement and E/A or E/E´ ratio above median manifested higher numbers of VPBs than rest of subjects (median 195 (IQR 31; 546) vs. 6 (3; 40); p = 0.02, and 195 (31; 274) vs. 14 (5; 54); p = 0.04, respectively). During follow-up 19 (7; 59) month, 19 (73%) of patients with cardiac AL amyloidosis died. The proportion of surviving patients was higher in subjects with QRS < 100ms and QTc < 450ms (both p < 0.05). Conclusion Standard 12-lead ECG seems to be method with excellent negative predictive value for exclusion of CA. Advanced CA is associated with higher number of both premature atrial and ventricular beats. QRS and QTc duration seems to be a marker of earlier mortality of patients with CA.

Autoři originálního textu ESC v plném znění:1,2 Alec Vahanian, Friedhelm Beyersdorf jménem autorů pracovní skupiny The Task Force for the Management of Valvular Heart Disease Evropské kardiologické společnosti (ESC) a Evropské společnosti kardiotorakální chirurgie (European Association for Cardio-Thoracic Surgery, EACTS).