Clinical application of CMR in cardiomyopathies: evolving concepts and techniques : A position paper of myocardial and pericardial diseases and cardiac magnetic resonance working groups of Italian society of cardiology.

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients' risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs.

Clinical course of hypertrophic cardiomyopathy patients implanted with a transvenous or subcutaneous defibrillator.

AIMS: The implantable cardioverter-defibrillator (ICD) is a life-saving therapy in patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death. Implantable cardioverter-defibrillator complications are of concern. The subcutaneous ICD (S-ICD) does not use transvenous leads and is expected to reduce complications. However, it does not provide bradycardia and anti-tachycardia pacing (ATP). The aim of this study was to compare appropriate and inappropriate ICD interventions, complications, disease-related adverse events and mortality between HCM patients implanted with a S- or transvenous (TV)-ICD. METHODS AND RESULTS: Consecutive HCM patients implanted with a S- (n = 216) or TV-ICD (n = 211) were enrolled. Propensity-adjusted cumulative Kaplan-Meier curves and multivariate Cox proportional hazard ratios were used to compare 5-year event-free survival and the risk of events. The S-ICD patients had lower 5-year risk of appropriate (HR: 0.32; 95%CI: 0.15-0.65; P = 0.002) and inappropriate (HR: 0.44; 95%CI: 0.20-0.95; P = 0.038) ICD interventions, driven by a high incidence of ATP therapy in the TV-ICD group. The S- and TV-ICD patients experienced similar 5-year rate of device-related complications, albeit the risk of major lead-related complications was lower in S-ICD patients (HR: 0.17; 95%CI: 0.038-0.79; P = 0.023). The TV- and S-ICD patients displayed similar risk of disease-related complications (HR: 0.64; 95%CI: 0.27-1.52; P = 0.309) and mortality (HR: 0.74; 95%CI: 0.29-1.87; P = 0.521). CONCLUSION: Hypertrophic cardiomyopathy patients implanted with a S-ICD had lower 5-year risk of appropriate and inappropriate ICD therapies as well as of major lead-related complications as compared to those implanted with a TV-ICD. Long-term comparative follow-up studies will clarify whether the lower incidence of major lead-related complications will translate into a morbidity or survival benefit.

A systematic review on focal takotsubo syndrome: a not-so-small matter.

A focal contraction pattern in takotsubo syndrome (TTS) is considered rare. Due to its peculiar presentation, which includes segmental left ventricular (LV) regional wall motion abnormalities (RWMA), the focal TTS pattern may be hardly differentiable from other entities, such as myocarditis or myocardial infarction. We performed a comprehensive systematic literature review researching for works in English published in Journals indexed in Embase, available online for consultation, using the following keywords (in Title and/or Abstract): ("takotsubo" OR "broken heart" OR "apical ballooning" OR "stress cardiomyopathy") AND ("focal" OR "atypical" OR "variant" OR "segments"). Thirty-three papers were retrieved: 17 case reports, 6 case series, and 10 population studies-with a total of 166 focal TTS patients. Prevalence of focal TTS ranged between 0.1% and 14% (pooled mean: 2.8%). Mean age of onset (58 years), gender distribution (80% of females), and type of triggers appeared similar to those reported in typical TTS. RWMA more frequently involved the interventricular septum and the anterolateral LV segments, with often preserved LV ejection fraction. In the majority of focal TTS reports that included adequate ECG information (n = 13), abnormalities were localized and not diffuse, always matching RWMA, and in 3 cases, reciprocal changes were observed. No in-hospital nor long-term deaths were reported. The focal TTS contraction pattern may be more prevalent than currently reported. Though possibly presenting with similar demographic background compared with typical TTS, the focal variant might be characterized by peculiar ECG modifications and better prognosis.

Long-term management of Takotsubo syndrome: a not-so-benign condition.

Takotsubo syndrome (TTS) is an intriguing clinical entity, characterized by usually transient and reversible abnormalities of the left ventricular systolic function, mimicking the myocardial infarction with non-obstructive coronary arteries. TTS was initially regarded as a benign condition, however recent studies have unveiled adverse outcomes in the short- and long-term, with rates of morbidity and mortality comparable to those experienced after an acute myocardial infarction. Given the usual transient nature of TTS, this is an unexpected finding. Moreover, long-term mortality seems to be mainly driven by non-cardiovascular causes. The uncertain long-term prognosis of TTS warrants a comprehensive outpatient follow-up after the acute event, although there are currently no robust data indicating its modality and timing. The aim of the present review is to summarize recent available evidence regarding long-term prognosis in TTS. Moreover methods, timing and findings of the long-term management of TTS will be discussed.

The natural history of hypertrophic cardiomyopathy.

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life.

265 Incidence, determinants and prognostic relevance of HS-troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Aims: myocardial involvement in the course of Coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. Aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. Methods and results: in this multicenter observational study, we analyzed data from n = 111 COVID-19 patients admitted to dedicated "COVID-19" medical units. Hs-Troponin was assessed in n = 103 patients and NP in n = 82 patients on admission; subgroups were identified according to values beyond reference range. increased hs-Troponin and NP were found in 38% and 56% of the cases respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP only (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03 respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B=-0.212, p = 0.013 and B = 0.179, p = 0.037 respectively), and of NP with age and previous CVD (B = 0.480, p < 0.001 and B = 0.253, p = 0.001 respectively). In patients with in-hospital mortality (n = 23, 21%) hs-Troponin and NP were both higher (p = 0.001 and p = 0.002 respectively), while increasing hs-troponin and NP were associated with worse in-hospital prognosis [OR 4.88 (95% CI 1.9-12.2), p = 0.001 (adjusted OR 3.1 (95% CI 1.2-8.5), p = 0.025) and OR 4.67 (95% CI 2-10.8), p < 0.001 (adjusted OR 2.89 (95% CI 1.1-7.9), p = 0.04) respectively]. Receiver operator characteristic curves showed good ability of hs-Troponin and NP in predicting in-hospital mortality (AUC = 0.869 p < 0.001 and AUC = 0.810, p < 0.001 respectively). Conclusion: myocardial involvement at admission is common in COVID-19 pneumonia and associated to worse prognosis, suggesting a role for cardiac biomarkers assessment in COVID-19 risk stratification. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point towards existing different mechanisms leading to their elevation in this setting.

Clinical outcomes in adult athletes with hypertrophic cardiomyopathy: a 7-year follow-up study.

OBJECTIVE: Current guidelines recommend precautionary disqualification from competitive sports in patients with hypertrophic cardiomyopathy (HCM). We assessed the incidence of cardiovascular events in a cohort of patients with HCM engaged in long-term exercise programmes and competitive sport. METHODS: We reviewed data on 88 consecutive athletes diagnosed with HCM, from 1997 to 2017; 92% male, 98% Caucasian, median age 31 (IQR: 19-44) years. All participated in regular exercise programmes and competitive sport at study entry.We performed follow-up evaluation after 7±5 (1-21) years. 61 (69%) of the athletes had substantially reduced or stopped exercise and sport (ie, HCM-detrained), and 27 had continued with regular training and sport competitions (HCM-trained). At baseline evaluation, both groups were similar for age, gender balance, symptoms, ECG abnormalities, extent of left ventricular hypertrophy, arrhythmias and risk profile for sudden cardiac death/arrest. RESULTS: During the follow-up period, two participants suffered sudden cardiac arrest or death (0.3% per year) both outside of sport participation. In addition, 19 (22%) reported symptoms (syncope in 3, palpitations in 10, chest pain in 4 and dyspnoea in 2). The Kaplan-Meier analyses of freedom from combined sudden cardiac arrest/death and symptoms (log-rank test p=0.264) showed no differences between HCM-trained and detrained patients. CONCLUSION: In this adult cohort of low-risk HCM athletes, voluntary decision to pursue in participation in competitive sport events was not associated with increased risk for major cardiac events or clinical worsening compared with decision to reduce or withdraw from exercise programmes and sport. Similar results may not be seen in younger or racially diverse athlete populations, or in patients with more severe HCM phenotypes.

Safety and efficacy of anti-tachycardia pacing in patients with hypertrophic cardiomyopathy implanted with an ICD.

BACKGROUND: In hypertrophic cardiomyopathy (HCM) patients implanted with an implantable cardioverter defibrillator (ICD), clinical outcomes of antitachycardia pacing (ATP) have been poorly explored. In a retrospective analysis of a cohort of consecutive HCM patients implanted with an ICD, we aimed to assess the efficacy, safety, and clinical value of ATP. METHODS: The cohort of HCM patients implanted with a transvenous ICD and followed in our center was assessed for device intervention from implantation to last clinical follow-up. RESULTS: Overall 77 patients (45 males; mean age: 46 ± 16 years) were analyzed. After 67 ± 41 months, 24 patients had 49 ventricular tachycardia/fibrillation (VT/VF) appropriately treated (5.8% per year). Among 39 monomorphic VTs, ATP was effective in 27 (success rate: 69%). Mean time from VT onset to ATP delivery was 9.1 ± 4.9 s. The only clinical variable improving ATP success was use of beta-blockers (81% vs 50%; P = .04). Out of 12 ineffectively treated VTs, one was immediately shocked, four self-terminated after 18 ± 12 s, and seven (18%) were accelerated to a new VT. ATP was also delivered for 27 of 42 inappropriately detected episodes and induced two de novo VTs (7%). In the per patient analysis, 14 out 77 (18%) patients had one or more appropriate and effective ATP (3.4% per year), and only six (8%; 1.4% per year) received more than one ATP. CONCLUSION: ATP is moderately effective for the treatment of monomorphic VTs in HCM patients. However, the rate of appropriate ATP therapies is low, ATP is often prematurely delivered, and ATP-induced arrhythmia degeneration is of concern.

RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD Patients with Heart Failure.

BACKGROUND: Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD). METHODS AND RESULTS: A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of primary prevention patients free from any appropriate ICD intervention after 43 ± 25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from Cox proportional-hazards regression analysis. In all, 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI: 0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P = 0.08), and underuse of ß-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After adjustment for age, sex, AF, and use of ß-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P = 0.02). CONCLUSIONS: Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF.

Spatial QT Dispersion Predicts Nonsustained Ventricular Tachycardia and Correlates with Confined Systodiastolic Dysfunction in Hypertrophic Cardiomyopathy.

OBJECTIVES: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. METHODS: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QTe), Q-Tpeak, Tpeak-Tend (TpTe), J-Tpeak, and J-Tend. RESULTS: The NSVT group showed only QTe dispersion and TpTe dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p=0.021) and QTe Bazett dispersion (p=0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p=0.0004). CONCLUSION: Our data support QTe dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QTe dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.

Electrocardiographic evolution in patients with hypertrophic cardiomyopathy who develop a left ventricular apical aneurysm.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with apical aneurysm have a largely unfavourable clinical course, and are often unrecognised because echocardiography is limited in the assessment of the left ventricular (LV) apex. The aim of this study is the identification of electrocardiographic (ECG) abnormalities associated with the development of apical aneurysm in HCM patients. MATERIALS AND METHODS: Electrocardiographic features were assessed in 14 HCM patients who had a good-quality baseline ECG recorded before and after the diagnosis of apical aneurysm. RESULTS: During follow-up (8.8±7.5years), the following ECG changes were observed: increase in QRS-complex duration (87±12ms to 118±34ms, p=0.006), QRS-complex fragmentation, decrease in QRS-complex amplitude (SV1+RV5-6, from 41±18mm to 26±11mm, p=0.015), ST-segment elevation in V4-V6 (J-point in V5, from -0.9±1.3mm to +0.7±1.3, p=0.003), positivisation of negative T waves in V3-V6 (T-wave depth in V5, from -3.4±6.6 to +3.1±4.1, p=0.005). CONCLUSIONS: HCM patients who develop LV apical aneurysm exhibit distinctive ECG changes along with apical remodelling. Suggestive ECGs should lead the physician to study LV apex by nonstandard echocardiographic views, and perform MRI.

Myocardial repolarization dispersion and late gadolinium enhancement in patients with hypertrophic cardiomyopathy.

BACKGROUND: Growing evidence suggests that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) is an additive marker of disease severity, and possibly of arrhythmic risk, in hypertrophic cardiomyopathy (HCM). We investigated the possible relationship between LGE and markers of myocardial repolarization dispersion in HCM. METHODS AND RESULTS: Eighty-five HCM outpatients underwent CMR and short-period electrocardiogram analysis to calculate the temporal myocardial repolarization dispersion through the QT variance normalized for QT mean (QTVN) and the QT variability index (QTVI). The QT dispersion in the spatial domain was also obtained. Patients with LGE (62%) had higher left atrial volume, maximum wall thickness, and left ventricular mass (P<0.0001), as well as a greater prevalence of non-sustained ventricular tachycardia (P<0.0001) and hypotensive blood pressure response (P=0.044). Both QTVN and QTVI were higher in the group with LGE (P<0.0001). At multivariate analysis, using QTVI as the dependent variable, %LGE (P<0.0001), age (P<0.0001), left ventricular outflow obstruction (P=0.038), and sudden cardiac death risk factor burden (P=0.020) reached statistical significance. Otherwise, only %LGE (P=0.005) and left ventricular mass index (P=0.015) remained associated with QTVN. CONCLUSIONS: Temporal myocardial repolarization dispersion correlates with LGE extent. Whether these variables could be useful in HCM clinical management warrants confirmation by larger prospective studies.

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis.

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

Myocardial oedema contributes to interstitial expansion and associates with mechanical and electrocardiographic changes in takotsubo syndrome: a CMR T1 and T2 mapping study.

AIMS: myocardial oedema is largely represented in takotsubo syndrome (TTS) and may contribute to alter the myocardium morphology and function. The aim of the study is to describe relationships between oedema, mechanical, and electrical abnormalities in TTS. METHODS AND RESULTS: the study included n = 32 hospitalized TTS patients and n = 23 controls. Cardiac magnetic resonance (CMR) with tissue mapping and feature tracking was performed with concomitant 12-lead electrocardiogram (ECG) recording. Mean age of TTS was 72 ± 12 years old, 94% women. Compared with controls, patients had higher left ventricular (LV) mass, worse systolic function, higher septal native T1 (1116 ± 73 msec vs. 970 ± 23 msec, P < 0.001), T2 (56 ± 5 msec vs. 46 ± 2 msec, P < 0.001), and extracellular volume (ECV) fraction (32 ± 5% vs. 24 ± 1%, P < 0.001). TTS patients had higher apicobasal gradient of T2 values (12 ± 6 msec vs. 2 ± 6 msec, P < 0.001); basal LV wall displayed higher native T1, T2, and ECV (all P < 0.002) but similar circumferential strain against controls (-23 ± 3% vs. -24 ± 4%, P = 0.351). In the TTS cohort, septal T2 values showed significant correlations with native T1 (r = 0.609, P < 0.001), ECV (r = 0.689, P < 0.001), left ventricular ejection fraction (r = -0.459, P = 0.008) and aVR voltage (r = -0.478, P = 0.009). Negative T-wave voltage and QTc length correlated with apicobasal T2 mapping gradient (r = 0.499, P = 0.007 and r = 0.372, P = 0.047, respectively) but not with other tissue mapping measurements. CONCLUSIONS: CMR T1 and T2 mapping demonstrated increased myocardial water content conditioning interstitial expansion in acute TTS, detected even outside areas of abnormal wall motion. Oedema burden and distribution associated with mechanical and electrocardiographic changes, making it a potential prognostic marker and therapeutic target in TTS.

Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning.

Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations.

BACKGORUND: Hereditary transthyretin(vATTR) cardiac amyloidosis has extremely different features according to the type of transthyretin(TTR) mutation. Data about electrocardiographic findings(ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR, focusing on different TTR mutations. METHODS AND RESULTS: This is a multicentric, retrospective, observational study performed in six Italian referral centres. We divided patients in two groups, according to the previously described phenotypic manifestations of the TTR mutation. Of 64 patients with vATTR, 23(36%) had prevalent cardiac(PC) TTR mutations and 41(64%) patients had a prevalent neurological(PN) TTR mutations. Patients with PC mutations were more frequently males and older, with advanced NAC staging. At baseline ECG, atrial fibrillation was more common in patients with PC, while pacemaker induced rhythm in PN mutations. PQ and QRS durations were longer and voltage to mass ratio was lower in PC mutations. Different TTR mutations tend to have distinctive ECG features. CONCLUSIONS: ECG in vATTR is extremely heterogeneous and the specific mutations are associated with distinct instrumental and clinical features. The differences between PN and PC vATTR are only partially explained by the different degree of cardiac infiltration.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

The Diagnostic Value of the 12-Lead ECG in Arrhythmogenic Left Ventricular Cardiomyopathy: Novel ECG Signs.

BACKGROUND: Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series. OBJECTIVES: This study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data. METHODS: We reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance. RESULTS: T-wave inversion was often noted (57.4%), particularly in the inferior and lateral leads. Low QRS voltages in limb leads were observed in 22.2% of patients. The following novel ECG findings were identified: left posterior fascicular block (LPFB) (20.4%), pathological Q waves (33.3%), and a prominent R-wave in V1 with a R/S ratio ≥0.5 (24.1%). The QRS voltages were lower in ALVC compared with controls, particularly in lead I and II. At receiver-operating characteristic analysis, the sum of the R-wave in I to II ≤8 mm (AUC: 0.909; P < 0.0001) and S-wave in V1 plus R-wave in V6 ≤12 mm (AUC: 0.784; P < 0.0001) effectively discriminated ALVC patients from controls. It is noteworthy that 4 of the 8 patients with an apparently normal ECG were recognized by these new signs. Transmural late gadolinium enhancement was associated to LPFB, a R/S ratio ≥0.5 in V1, and inferolateral T-wave inversion, and a ringlike pattern correlated to fragmented QRS, SV1+RV6 ≤12 mm, low QRS voltage, and desmoplakin alterations. CONCLUSIONS: Pathological Q waves, LPFB, and a prominent R-wave in V1 were common ECG signs in ALVC. An R-wave sum in I to II ≤8 mm and SV1+RV6 ≤12 mm were specific findings for ALVC phenotypes compared with controls.

Relation of delayed intrinsicoid deflection of the QRS complex to sudden cardiac death in patients with hypertrophic cardiomyopathy.

AIMS: Predictors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) do not include ECG variables. Intrinsicoid deflection (ID) represents the early ventricular depolarization on surface ECG. Delayed ID (DID) has been associated with sudden cardiac arrest (SCA) in the community. In a cohort of consecutive patients with HCM, we assessed whether DID predicts SCA or its surrogates. METHODS: We reviewed ECG, clinical and follow-up data of 344 consecutive HCM patients. DID (ID ≥50 ms) was classified as lateral (leads I or aVL), inferior (leads II, III or aVF), and precordial (leads V5 or V6). The endpoint was a combination of SCD, resuscitated SCA or appropriate ICD intervention. RESULTS: The SCA group was composed by 2 secondary prevention ICD recipients and 23 patients that reached the endpoint during follow-up (108 ± 73 months). SCA patients had more frequently massive LV hypertrophy (LVH) or end-stage HCM. ECG indexes of LVH were comparable between SCA and controls. SCA patients were more likely to have DID on ECG lateral leads I/aVL (72% vs 44%; p = 0.008). A non significant trend was observed for inferior and V5/V6 leads. DID I/aVL was associated with SCA in multivariate analysis after correction for massive LVH and end-stage disease (HR: 2.86; 95%CI: 1.14-7.13; p = 0.02). CONCLUSIONS: In HCM patients DID is associated with increased risk of SCA. Its prognostic value extends beyond that of LVH. If confirmed in prospective studies, the prognostic power of this ECG marker could be used to refine risk prediction.

CHA2DS2-VASc score in patients with COVID-19 pneumonia and its relationship with biomarkers of thrombosis, inflammation and myocardial injury.

CHA2DS2-VASC score associates with worse prognosis in coronavirus-disease-19 (COVID-19). This study investigated laboratory correlates of increasing CHA2DS2- VASc in patients with COVID-19. Patients with COVID-19 were stratified by CHA2DS2-VASc (Group 1: CHA2DS2-VASc 0-1; Group 2: CHA2DS2-VASc 2-3; Group 3: CHA2DS2-VASc ≥4). We found stepwise increase of D-dimer, hs-Troponin and in-hospital mortality across groups (all P < 0.01). D-dimer and hs-Troponin remained independently associated with CHA2DS2-VASc (B = 0.145, P = 0.03; B = 0.320, P < 0.001, respectively). We found significant correlations between D-dimer and C-reactive protein (CRP) in Group 1 and 2, not in Group 3 (r2 = 0.103, P = 0.005; r2 = 0.226, P = 0.001; r2 = 0.021, P = 0.253 respectively), and between D-dimer and hs-Troponin in group 2 and 3, not in Group 1 (r2 = 0.122, P = 0.003; r2 = 0.120, P = 0.007; r2 = 0.006, P = 0.514 respectively). In our cohort, CHA2DS2- VASc was independently associated with D-dimer and hs- Troponin increase. Variable relationships of D-dimer with hs-Troponin and CRP within different CHA2DS2-VASc strata suggest multiple mechanisms to be responsible for D-dimer increase in COVID-19.