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AIMS: Non-ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti-inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro-fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive. METHODS AND RESULTS: Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n = 3289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long-term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow-up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4 ± 0.7 mmHg*min/ml in NICMP vs. 6.7 ± 0.8 mmHg*min/ml in NICMP/Mpo-/-mice, n = 8, p = 0.006, data expressed as mean ± standard error of the mean) and improved left ventricular function (LVEF 30.3 ± 2.2% in NICMP vs. 40.7 ± 1.1% in NICMP/Mpo-/- mice, n = 16, p < 0.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12 weeks showed increase in LVEF, decline in natriuretic peptides and improved 6-min walking distance. MPO inhibitor-related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort. CONCLUSIONS: Myeloperoxidase predicts long-term outcome in HFrEF and its inhibition elicits systemic anti-inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF.

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International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.

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AIMS: We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. CONCLUSION: In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

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AIMS: The usefulness of coronary venous system mapping has been reported for assessing intramural and epicardial substrates in patients with scar-related ventricular tachycardia (VT). However, there has been little data on mapping from coronary arteries. We investigated the safety and utility of mapping from coronary arteries with a novel over-the-wire multielectrode catheter in scar-related VT patients. METHODS AND RESULTS: Ten consecutive scar-related VT patients with non-ischaemic cardiomyopathy who underwent mapping from a coronary artery were analysed. Six patients underwent simultaneous coronary venous mapping. High-density maps were created by combining the left ventricular endocardium and coronary vessels. Substrate maps were created during the baseline rhythm with 2438 points (IQR 2136-3490 points), including 329 (IQR 59-508 points) in coronary arteries. Abnormal bipolar electrograms were successfully recorded within coronary arteries close to the endocardial substrate in seven patients. During VT, isthmus components were recorded within the coronary vessels in three patients with no discernible isthmus components on endocardial mapping. The ablation terminated the VT from an endocardial site opposite the earliest site in the coronary arteries in five patients. CONCLUSION: The transcoronary mapping with an over-the-wire multielectrode catheter can safely record abnormal bipolar electrograms within coronary arteries. Additional mapping data from the coronary vessels have the potential to assess three-dimensional ventricular substrates and circuit structures in scar-related VT patients.

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AIMS: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). METHODS AND RESULTS: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months. CONCLUSION: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

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Coronavirus 19 (COVID-19) is well known for causing acute respiratory distress syndrome. Among other systemic complications, myocarditis is a frequently reported presentation as well as complication. One systematic review reported a 14% mortality rate in patients with COVID-19 myocarditis. Endomyocardial biopsy is a definitive diagnostic test but has been a challenge to perform in most cases of COVID myocarditis due to the contagious nature of the disease. Patients presenting with new cardiomyopathy with troponin leak and arrhythmias, supported by recent COVID-19 diagnosis should be suspected for COVID-induced myocarditis. Supportive treatment has been the mainstay of treatment with limited data on immunotherapy and colchicine. Our case is about a male in his 50s who had a cardiac arrest due to ventricular fibrillations, with a positive COVID-19 test. Further workup showed severe non-ischaemic cardiomyopathy with an EF of 15-20%. He was treated with intravenous immunotherapy and colchicine. A repeat echocardiogram 3 days later showed resolution of cardiomyopathy. Our case report highlights the possible beneficial effects of immunotherapy and colchicine in viral myocarditis. LEARNING POINTS: Myocarditis should be suspected in patients with acute onset cardiomyopathy with troponin leak and no evidence of ischaemia. COVID-19 myocarditis can present with arrhythmia, which could be fatal in some cases.Even though supportive management is the mainstay of treatment for COVID-19 myocarditis, there have been reports of benefits of intravenous immunotherapy (IVIG) and colchicine.More studies are warranted to explore the beneficial effects of IVIG and colchicine not just in COVID-19 myocarditis, but also in other viral causes of myocarditis he aim of this study is also to raise awareness among healthcare professionals about the Bentall procedure in patients with type A aortic dissection involving the aortic valve.

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BACKGROUND: Cardiac magnetic resonance imaging may provide a non-invasive alternative to coronary angiography for differentiating between ischaemic and non-ischaemic cardiomyopathy in cases of unexplained reduced left ventricular ejection fraction. AIM: The CAMAREC study aims to evaluate the diagnostic accuracy of cardiac magnetic resonance imaging in predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, using coronary angiography as the gold standard for comparison. METHODS: CAMAREC is a prospective cohort study of 406 patients in 10 centres with newly diagnosed, unexplained left ventricular ejection fraction ≤ 45%. Cardiac magnetic resonance imaging and coronary angiography will be conducted within a 2-week interval, starting with cardiac magnetic resonance imaging; independent committees will review the results blindly. Primary outcome is sensitivity of detecting ischaemic scar on cardiac magnetic resonance imaging for predicting significant coronary artery disease on coronary angiography according to Felker's criteria. Secondary outcomes include specificity and positive and negative predictive values (with 95% confidence intervals) of cardiac magnetic resonance imaging for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, kappa concordance coefficient between cardiac magnetic resonance imaging and coronary angiography for diagnosing the affected myocardial territory, and the impact of cardiac magnetic resonance imaging on revascularization decisions. Two ancillary studies will evaluate the incremental cost-effectiveness of using cardiac magnetic resonance imaging first versus coronary angiography first, and the sensitivity of pre- and postcontrast T1-mapping for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction. CONCLUSION: Our study protocol is designed to rigorously evaluate cardiac magnetic resonance imaging as a non-invasive alternative to coronary angiography in patients with unexplained reduced left ventricular ejection fraction. The results will have significant implications for patient management, and may support growing evidence for the clinical utility of cardiac magnetic resonance imaging.

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BACKGROUND: By definition, dilated cardiomyopathy (DCM) is characterized by enlargement of the left ventricular (LV) cavity, and systolic dysfunction. However, in 2016 ESC introduced a new clinical entity - hypokinetic non-dilated cardiomyopathy (HNDC). HNDC is defined as LV systolic dysfunction without LV dilatation. However, the diagnosis of HNDC has so far rarely been made by a cardiologist, and it is unknown whether "classic" DCM differs from HNDC in terms of clinical course and outcomes. OBJECTIVES: Comparison of heart failure profiles and outcomes between patients with "classic" dilated (DCM) and HNDCs. METHOD: We retrospectively analysed 785 DCM patients, defined as impaired left ventricle (LV) systolic function (ejection fraction [LVEF] <45%) in the absence of coronary artery disease, valve disease, congenital heart disease, and severe arterial hypertension. "Classic" DCM was diagnosed when LV dilatation was present (LV end-diastolic diameter >52 mm/58 mm in women/men); otherwise, HNDC was diagnosed. After 47 ± 31 months, the all-cause mortality and composite endpoint (all-cause mortality, heart transplant - HTX, left ventricle assist device implantation - LVAD) were assessed. RESULTS: There were 617 (79%) patients with LV dilatation. Patients with "classic" DCM differed from HNDC in terms of clinically relevant parameters [hypertension (47% vs. 64%, p = 0.008), ventricular tachyarrhythmias (29% vs. 15%, p = 0.007), NYHA class (2.5 ± 0.9 vs. 2.2 ± 0.8, p = 0.003)], had lower cholesterol (LDL: 2.9 ± 1.0 vs. 3.2 ± 1.1 mmol/L, p = 0.049), and higher N-terminal pro-brain natriuretic peptide (3,351 ± 5,415 vs. 2,563 ± 8584 pg/mL, p = 0.0001) and required higher diuretics dosages (57.8 ± 89.5 vs. 33.7 ± 48.7 mg/day, p ≤ 0.0001). All of their chambers were larger (LVEDd: 68.3 ± 4.5 vs. 52.7 ± 3.5 mm, p < 0.0001) and they had lower LVEF (25.2 ± 9.4 vs. 36.6 ± 11.7%, p < 0.0001). During the follow-up, there were 145 (18%) composite endpoints ("classic" DCM vs. HNDC: 122 [20%] vs. 26 [18%], p = 0.22): deaths (97 [16%] vs. 24 [14%], p = 0.67), HTX (17 [4%] vs. 4 [4%], p = 0.97) and LVAD (19 [5%] vs. 0 [0%], p = 0.03). Both groups did not differ in terms of all-cause mortality (p = 0.70), cardiovascular (CV) mortality (p = 0.37) and composite endpoint (p = 0.26). CONCLUSIONS: LV dilatation was absent in more than one-fifth of DCM patients. HNDC patients had less severe heart failure symptoms, less advanced cardiac remodelling, and required lower diuretics dosages. On the other hand, "classic" DCM and HNDC patients did not differ in terms of all-cause mortality, CV mortality, and composite endpoint.

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AIM: To compare the risk of ventricular arrhythmias (VA) and sudden death (SD) between New York Heart Association (NYHA) class I and NYHA class II-III patients with non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Observational retrospective cohort study including patients with NICM who underwent cardiac magnetic resonance at two hospitals. The primary endpoint included appropriate implantable cardioverter defibrillator (ICD) therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. The secondary endpoint included heart failure (HF) hospitalizations, heart transplant, left ventricular assist device implant or HF death. Overall, 698 patients were included, 33% in NYHA class I. During a median follow-up of 31 months, the primary endpoint occurred in 57 patients (8%), with no differences between NYHA class I and NYHA class II-III cases (7% vs. 9%, p = 0.62). Late gadolinium enhancement (LGE) was the only independent predictor of the primary outcome both in NYHA class I and NYHA class II-III patients. LGE+ NYHA class I patients had a similar cumulative incidence of the primary endpoint as compared to LGE+ NYHA class II-III (p = 0.92) and a significantly higher risk as compared to LGE- NYHA class II-III cases (p < 0.001). The risk of the secondary endpoint was significantly higher in patients in NYHA class II-III as compared to those in NYHA class I (hazard ratio 3.2, p = 0.001). CONCLUSIONS: Patients with NICM in NYHA class I are not necessarily at low risk of VA and SD. Actually, LGE+ NYHA class I patients have a high risk. NYHA class I patients with high-risk factors, such as LGE, could benefit from primary prevention ICD at least as much as those in NYHA class II-III with the same risk factors.

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AIM: The aim of this research was to evaluate the prognostic value of myocardial scar using cardiac magnetic resonance (CMR) imaging in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM). METHODS: One hundred and fifty-four patients with either ICM or NICM underwent CMR with late gadolinium enhancement sequences for assessment of left ventricular ejection fraction (LVEF), and detection and quantification of any myocardial scar using three methods: manual, number of segments involved, and percentage of scarred myocardium. Patients were followed up for at least six months for clinical cardiac events. RESULTS: Patients were divided into two groups: group I, patients with ICM (58%) and group II, those with NICM (42%). Clinical presentation ranged from eventless lpar;10%) to chest pain (18%), heart failure (15%), hospitalisation (35%), syncope (1%), ventricular tachycardia (< 1%) and cardiac arrest (< 1%). The scar mass was larger in size in group I (17 ± 15%) than in group II (8 ± 13%). A direct relationship was observed between scar size and event severity (p < 0.001). An inverse relationship between LVEF and event severity was found in group I (p < 0.001) but not in group II (p = 0.128). CONCLUSIONS: Myocardial scar size was a strong predictor of clinical outcome in both the ICM and NICM patients. LVEF was less reliable in predicting morbidity in cardiomyopathy patients.

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BACKGROUND: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis. METHODS: Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. RESULTS: Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3­years follow-up was 3.7% yielding a number needed to treat of 27. CONCLUSION: ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker.

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AIMS: To evaluate whether cardiac magnetic resonance (CMR)-based parametric mapping and strain analysis can improve the risk-stratification for ventricular arrhythmias (VA) and sudden death (SD) in non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Secondary analysis of a prospective single-centre-registry (NCT02326324), including 703 consecutive NICM patients, 618 with extracellular volume (ECV) available. The combined primary endpoint included appropriate implantable cardioverter defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. During a median follow-up of 21 months, 14 patients (2%) experienced the primary endpoint. Native T1 was not associated with the primary endpoint. Left ventricular global longitudinal strain lost its significant association after adjustment for left ventricular ejection fraction (LVEF). Among patients with ECV available, 11 (2%) reached the primary endpoint. Mean ECV was significantly associated with the primary endpoint and the best cut-off was 30%. ECV ≥ 30% was the strongest independent predictor of the primary endpoint (hazard ratio 14.1, P = 0.01) after adjustment for late gadolinium enhancement (LGE) and LVEF. ECV ≥ 30% discriminated the arrhythmic risk among LGE+ cases and among those with LVEF ≤ 35%. A simple clinical risk-stratification model, based on LGE, LVEF ≤ 35% and ECV ≥ 30%, achieved an excellent predictive ability (Harrell's C 0.82) and reclassified the risk of 32% of the study population as compared to LVEF ≤ 35% alone. CONCLUSIONS: Comprehensive CMR evaluation in NICM showed that ECV was the only parameter with an independent and strong predictive value for VA/SD, on top of LGE and LVEF. A risk-stratification model based on LGE, LVEF ≤ 35% and ECV ≥ 30% achieved an excellent predictive ability for VA/SD. CLINICAL TRIAL REGISTRATION: UHSM CMR study (NCT02326324) https://clinicaltrials.gov/ct2/show/NCT02326324.

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BACKGROUND: There are differences in substrate and ablation approaches for ventricular tachycardia (VT) in ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). OBJECTIVE: To perform a systematic review and meta-analysis comparing clinical and procedural characteristics/outcomes of VT ablation in ICM versus NICM. METHODS: Electronic databases were searched for comparative studies reporting outcomes of VT ablation in patients with ICM and NICM. Primary outcomes were acute procedural success, VT recurrence and long-term mortality. Meta-analyses were performed using random-effects modelling. RESULTS: Thirty-one (31) studies (7,473 patients; 4,418 ICM and 3,055 NICM) were included. Patients with ICM were significantly older (67.0 vs 55.3 yrs), more commonly male (89% vs 79%), had lower left ventricular ejection fraction (29% vs 38%) were less likely to undergo epicardial access (11% vs 36%) and were more likely to require haemodynamic support during ablation (relative risk [RR] 1.30; 95% CI 1.01-1.69). Acute procedural success (i.e. non-inducibility of VT) was higher in the ICM cohort (RR 1.10, 95% CI 1.05-1.15). Recurrence of VT at follow-up was significantly lower in the ICM cohort (RR 0.77; 95% CI 0.70-0.84). Peri-procedural mortality, incidence of procedural complications and long-term mortality were not significantly different between the cohorts. CONCLUSIONS: NICM and ICM patients undergoing VT ablation are fundamentally different in their clinical characteristics, ablation approaches, acute procedural outcomes and likelihood of VA recurrence. VT ablation in NICM has a lower likelihood of procedural success with increased risk of VA recurrence, consistent with known challenging arrhythmia substrate.

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AIMS: Sepsis-induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR). METHODS AND RESULTS: Fifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady-state free precession imaging was performed for evaluation of cardiac anatomy and function in long-axis and short-axis views. Native T1 maps (modified Look-Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid-ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high-sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in-hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow-up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01). CONCLUSIONS: Septic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo-like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff. TRIAL REGISTRATION: retrospectively registered (ISRCTN85297773).

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AIMS: The recent definition of heart failure with improved ejection fraction outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long-term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and their correlations with outcome in non-ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF). METHODS AND RESULTS: Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, and second evaluation showing both a ≥10% point increase from baseline LVEF and LVEF >40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow-up. The primary endpoint was a composite of all-cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (hazard ratio 2.54; 95% confidence interval 1.60-4.04). The association of declining LVEF with the risk of D/HT/LVAD was non-linear, with a steep increase up to 8% points reduction, then remaining stable. CONCLUSIONS: In NICM, a 57% rate of impEF was observed. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD.

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Adverse remodelling following an initial insult is the hallmark of heart failure (HF) development and progression. It is manifested as changes in size, shape, and function of the myocardium. While cardiac remodelling may be compensatory in the short term, further neurohumoral activation and haemodynamic overload drive this deleterious process that is associated with impaired prognosis. However, in some patients, the changes may be reversed. Left ventricular reverse remodelling (LVRR) is characterized as a decrease in chamber volume and normalization of shape associated with improvement in both systolic and diastolic function. LVRR might occur spontaneously or more often in response to therapeutic interventions that either remove the initial stressor or alleviate some of the mechanisms that contribute to further deterioration of the failing heart. Although the process of LVRR in patients with new-onset HF may take up to 2 years after initiating treatment, there is a significant portion of patients who do not improve despite optimal therapy, which has serious clinical implications when considering treatment escalation towards more aggressive options. On the contrary, in patients that achieve delayed improvement in cardiac function and architecture, waiting might avoid untimely implantable cardioverter-defibrillator implantation. Therefore, prognostication of successful LVRR based on clinical, imaging, and biomarker predictors is of utmost importance. LVRR has a positive impact on prognosis. However, reverse remodelled hearts continue to have abnormal features. In fact, most of the molecular, cellular, interstitial, and genome expression abnormalities remain and a susceptibility to dysfunction redevelopment under biomechanical stress persists in most patients. Hence, a distinction should be made between reverse remodelling and true myocardial recovery. In this comprehensive review, current evidence on LVRR, its predictors, and implications on prognostication, with a specific focus on HF patients with non-ischaemic cardiomyopathy, as well as on novel drugs, is presented.

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This review summarizes the results of clinical trials of cell therapy in patients with heart failure (HF). In contrast to acute myocardial infarction (where results have been consistently negative for more than a decade), in the setting of HF the results of Phase I-II trials are encouraging, both in ischaemic and non-ischaemic cardiomyopathy. Several well-designed Phase II studies have met their primary endpoint and demonstrated an efficacy signal, which is remarkable considering that only one dose of cells was used. That an efficacy signal was seen 6-12 months after a single treatment provides a rationale for larger, rigorous trials. Importantly, no safety concerns have emerged. Amongst the various cell types tested, mesenchymal stromal cells derived from bone marrow (BM), umbilical cord, or adipose tissue show the greatest promise. In contrast, embryonic stem cells are not likely to become a clinical therapy. Unfractionated BM cells and cardiosphere-derived cells have been abandoned. The cell products used for HF will most likely be allogeneic. New approaches, such as repeated cell treatment and intravenous delivery, may revolutionize the field. As is the case for most new therapies, the development of cell therapies for HF has been slow, plagued by multifarious problems, and punctuated by many setbacks; at present, the utility of cell therapy in HF remains to be determined. What the field needs is rigorous, well-designed Phase III trials. The most important things to move forward are to keep an open mind, avoid preconceived notions, and let ourselves be guided by the evidence.

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BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with potential major complications, including mortality. The risk of acute complications in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) has not been systematically evaluated. METHODS: PubMed was searched for studies of catheter ablation of VT published between September 2009 and September 2019. Pre-specified primary outcomes were (1) rate of major acute complications, including death, and (2) mortality rate. RESULTS: A total of 7395 references were evaluated for relevance. From this, 50 studies with a total of 3833 patients undergoing 4319 VT ablation procedures fulfilled the inclusion criteria (mean age 59 years; male 82%; 2363 [62%] ICM; 1470 [38%] NICM). The overall major complication rate in ICM cohorts was 9.4% (95% CI, 8.1-10.7) and NICM cohorts was 7.1% (95% CI, 6.0-8.3). Reported complication rates were highly variable between studies (ICM I2 = 90%; NICM I2 = 89%). Vascular complications (ICM 2.5% [95% CI, 1.9-3.1]; NICM 1.2% [95% CI, 0.7-1.7]) and cerebrovascular events (ICM 0.5% [95% CI, 0.2-0.7]; NICM, 0.1% [95% CI, 0-0.2]) were significantly higher in ICM cohorts. Acute mortality rates in the ICM and NICM cohorts were low (ICM 0.9% [95% CI, 0.5-1.3]; NICM 0.6% [95% CI, 0.3-1.0]) with the majority of overall deaths (ICM 75%; NICM 80%) due to either recurrent VT or cardiogenic shock. CONCLUSION: Overall acute complication rates of VT ablation are comparable between ICM and NICM patients. However, the pattern and predictors of complications vary depending on the underlying cardiomyopathy.

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BACKGROUND: The aetiology of heart failure may have different effects on right ventricular (RV) function, pulmonary pressures and RV afterload. Pulmonary arterial capacitance (PAC) and pulmonary artery pulsatility index (PAPi) are novel haemodynamic indices used in determining RV afterload and RV function, respectively. We aimed to investigate whether there was a difference in PAC and PAPi between ischaemic cardiomyopathy (ICMP) and non-ischaemic cardiomyopathy (NICMP) in patients with end-stage heart failure. METHODS AND RESULTS: A total of 215 subjects undergoing evaluation for heart transplantation or left ventricular (LV) assist device were classified into two groups: ICMP (n = 101) and NICMP (n = 114). The patients with LV ejection fraction ≤ 25% were included in the study. ICMP group had lower PAC and higher PAPi values compared to NICMP group [1.25 (0.82-1.86) vs. 1.58 (1.02-2.21), p = 0.002 and 3.4 (2.2-5.0) vs. 2.5 (1.7-4.0); p = 0.007]. Pulmonary vascular resistance, pulmonary artery systolic and mean pressure were higher in ICMP group compared to NICMP group [3.5 ± 1.8 vs. 2.9 ± 2.3, p = 0.004; 59.0 (42.0-73.0) vs. 46.0 (37.0-59.0), p < 0.001, 35.0 (27.0-46.0) vs. 31.0 (23.0-39.0), p = 0.002]. The patients with ICMP had higher tricuspid annular plane systolic excursion and less RV dilatation. ICMP was an independent risk factor for pulmonary hypertension (OR: 4.02, 95% CI: 1.13-14.24, p = 0.031). CONCLUSION: ICMP was associated with lower PAC and higher PAPi. These results indicated that an ischaemic aetiology is associated with higher RV afterload and better RV function in the end-stage heart failure.

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While the efficacy of the intracardiac defibrillators (ICDs) for primary prevention is not disputed, the relevant studies were carried out a long time ago. Most pertinent trials, including MADIT-II, SCD-Heft, and DEFINITE, recruited patients more than 20 years ago. Since then, improved therapeutic modalities including, in addition to cardiac resynchronization therapy, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and, most recently, inhibitors of sodium-glucose cotransporter 2, have lowered present-day rates of mortality and of sudden cardiac death. Thus, nowadays, ICD therapy may be less effective than previously reported, and not as beneficial as many people currently believe. However, criteria for ICD implantation remain very inclusive. The patient must (only) be symptomatic and have ejection fraction (EF) ≤ 35%. The choice of EF 35% is notable because the average EF in all large trials was much lower, and clinical benefit was mainly limited to EF ≤ 30%. This EF cut-off value defines a substantial portion of potential ICD recipients. It seems therefore reasonable to limit ICD eligibility criteria in the EF range 30-35% to patients at highest risk only. We discuss and present some rational criteria to assist the clinician in improving risk stratification for preventive ICD implantation.

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