Speckle-tracking global longitudinal strain predicts death and cardiovascular events in patients with systemic sclerosis.

Aims: Albeit often asymptomatic, heart involvement in systemic sclerosis (SSc) represents a negative prognostic factor, accounting for nearly one-fourth of all deaths. Global longitudinal strain (GLS) is accurate in detecting heart involvement in patients with SSc and no overt cardiac disease and allows early detection and longitudinal monitoring, but its association with clinical endpoints has not been tested so far. The primary outcome was the association between left and right GLS and mortality for all causes. The secondary outcome was the association between left and right GLS and hospitalizations. Methods and results: A prospective longitudinal study enrolling all consecutive patients with SSc without structural heart disease or previous cardiovascular event.A total of 164 patients were enrolled, of whom 19 (11.5%) died during follow-up and 48 (29.3%) were hospitalized. Both left (LV) and right ventricle (RV) GLS at enrolment were independently associated with an increased risk of death for all causes and hospitalizations. Patients with biventricular GLS impairment, respectively, had a 4.2-, 4.9-, and 13.9-fold increased risk of death when compared with patients with only LV, only RV, or no impairment (P < 0.001). The incidence of hospitalization in patients with biventricular GLS impairment was nearly four times higher when compared with patients with only LV or only RV impairment, and nine times higher when compared with normal biventricular GLS (P < 0.001). Conclusion: Biventricular GLS is associated with an increased risk of death and hospitalization in patients with SSc during a median of 3-year follow-up, acting as a reliable and accurate prognostic tool in everyday practice.

Novel Medical Treatments and Devices for the Management of Heart Failure with Reduced Ejection Fraction.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of "heart failure with reduced ejection fraction" (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Conduction system disease management in patients candidate and/or treated for the aortic valve disease: an Italian Survey promoted by Italian Association of Arrhythmology and Cardiac Pacing (AIAC).

BACKGROUND: Conduction system disorders represent a frequent complication in patients undergoing surgical (surgical aortic valve replacement, SAVR) or percutaneous (transcatheter aortic valve implantation, TAVI) aortic valve replacement. The purpose of this survey was to evaluate experienced operators approach in this clinical condition. METHODS: This survey was independently conducted by the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) and it consisted of 24 questions regarding the respondents' profile, the characteristics of participating centres, and conduction disease management in different scenarios. RESULTS: Fifty-five physicians from 55 Italian arrhythmia centres took part in the survey. Prophylactic pacemaker implantation is rare. In case of persistent complete atrioventricular block (AVB), 49% and 73% respondents wait less than one week before implanting a definitive pacemaker after SAVR and TAVI, respectively. In case of second degree AVB, the respondents wait some days more for definitive implantation. Respondents consider bundle branch blocks, in particular pre-existing left bundle branch block (LBBB), the worst prognostic factors for pacemaker implantation after TAVI. The implanted valve type is considered a relevant element to evaluate. In patients with new-onset LBBB and severe/moderate left ventricular systolic dysfunction, respondents would implant a biventricular pacemaker in 100/55% of cases, respectively. CONCLUSIONS: Waiting time before a definitive pacemaker implantation after aortic valve replacement has reduced compared to the past, and it is anticipated in TAVI vs. SAVR. Bundle branch blocks are considered the worse prognostic factor for pacemaker implantation after TAVI. The type of pacemaker implanted in new-onset LBBB patients without severe left ventricular systolic dysfunction is heterogeneous.

Complications of left bundle branch area pacing compared with biventricular pacing in candidates for resynchronization therapy: Results of a propensity score-matched analysis from a multicenter registry.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction, heart failure, and left bundle branch block. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among patients undergoing CRT are lacking. OBJECTIVE: The aim of this study was to compare the long-term risk of procedure-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. METHODS: This prospective, multicenter, observational study enrolled 668 consecutive patients (mean age 71.2 ± 10.0 years; 52.2% male; 59.4% with New York Heart Association class III-IV heart failure symptoms) with left ventricular ejection fraction 33.4% ± 4.3% who underwent BVP (n = 561) or LBBAP (n = 107) for a class I or II indication for CRT. Propensity score matching for baseline characteristics yielded 93 matched pairs. The rate and nature of intraprocedural and long-term post-procedural complications occurring during follow-up were prospectively collected and compared between the 2 groups. RESULTS: During a mean follow-up of 18 months, procedure-related complications were observed in 16 patients: 12 in BVP (12.9%) and 4 in LBBAP (4.3%) (P = .036). Compared with patients who underwent LBBAP, those who underwent BVP showed a lower complication-free survival (P = .032). In multivariate analysis, BVP resulted an independent predictive factor associated with a higher risk of complications (hazard ratio 3.234; P = .042). Complications related to the coronary sinus lead were most frequently observed in patients who underwent BVP (50.0% of all complications). CONCLUSION: LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with an indication for CRT.

Giant aneurysm of the left atrial appendage: a case report.

Background: Left atrial appendage aneurysm (LAAA) is a rare condition mostly due to congenital malformations or secondary causes (i.e. mitral regurgitation). Case summary: We present a case of a 47-year-old male with a history of atrial fibrillation treated with propafenone presented to our emergency department for palpitation and epigastric pain. The electrocardiogram showed atrial fibrillation at high ventricular rate and a new-onset left bundle branch block. Urgent coronary angiogram excluded coronary artery disease. Echocardiography and cardiac magnetic resonance revealed a giant LAAA. The electrocardiogram alterations were deemed secondary to aberrancy and treatment with class IC antiarrhythmic. The patient was discussed in the heart team, and considering his will to avoid surgery, he was managed conservatively with closed follow-up, anticoagulant and antiarrhythmic therapy, and internal loop recorder. At 1-year follow-up, he showed asymptomatic and without arrhythmias. Discussion: Few cases are described in the literature; therefore, there is uncertainty in treatment and prognosis. Diagnosis is achieved with multimodality imaging. Treatment can be surgical with aneurysmectomy or conservative with regular follow-up by imaging examinations and pharmacological therapy aimed to prevent complications such as thrombosis and arrhythmias. Since high-quality scientific data are lacking, shared decision-making is essential for the management of patients affected by LAAA. In our clinical case, our patient's will to not undergo surgery was considered, and therefore, a conservative management with strict follow-up and medications was chosen.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study.

BACKGROUND: There are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). OBJECTIVE: We assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. METHODS: This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. RESULTS: A total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0-122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. CONCLUSION: In patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

High-power short-duration catheter ablation of atrial fibrillation: is it really a new era? Comparison between new and old radiofrequency contact force-sensing catheters.

BACKGROUND: The clinical performance of high-power, short-duration (HPSD) pulmonary vein isolation (PVI) with the novel flexible tip TactiFlex™ (TFSE) catheter, as compared to standard-power, long-duration (SPLD) PVI using the TactiCath™ (TCSE) catheter among patients undergoing catheter ablation (CA) of atrial fibrillation (AF) is currently unknown. METHODS: We conducted a prospective, observational, single-centre study including 40 consecutive patients undergoing PVI for paroxysmal/persistent AF, using HPSD ablation with the novel TFSE catheter (HPSD/TFSE group). Based on propensity score-matching, forty patients undergoing SPLD PVI with the TCSE catheter were identified (SPLD/TCSE group). In the HPSD/TFSE group, RF lesions were performed by delivering 40-50 W for 10-20 s, while in the SPLD/TCSE group, RF power was 30-35 W, targeting a lesion size index (LSI) of 4.0-5.5. The co-primary study outcomes were time required to complete PVI and first pass isolation (FPI). RESULTS: PVI was achieved in 100% of patients in both groups, and no major adverse events were observed. Remarkably, PVI time was shorter in the HPSD/TFSE, compared to the SPLD/TCSE group(9 [7-9] min vs. 50 [37-54] min; p < 0.001), while FPI rate was non-significantly higher in the former group(91% [146/160] vs 83% [134/160]; p = 0.063). Shorter procedural (108 [91-120] min vs. 173 [139-187] min, p < 0.001), total RF (9 [7-11] min vs. 43 [32-53] min, p < 0.001), fluoroscopy times(15 [10-19] min vs. 18 [13-26] min, p = 0.014), and lower DAP (1461 [860-2181] vs. 7200 [3400-20,800], p < 0.001) were recorded in the HPSD/TFSE group. A higher average impedance drop was obtained with HPSD/TFSE CA(17[17-18]Ω vs. 16 [15-17] Ω, p < 0.001). CONCLUSIONS: In our initial clinical experience, HPSD PVI with the TFSE catheter proved faster than SPLD PVI with the TCSE catheter, at least equally effective in terms of FPI, and it was associated with greater impedance drop.

Characteristics and Clinical Value of Electroanatomic Voltage Mapping in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidoses (CAs) are an increasingly recognised group of infiltrative cardiomyopathies associated with high risk of adverse cardiac events. We sought to characterise the characteristics and clinical value of right ventricular (RV) electroanatomic voltage mapping (EVM) in CA. METHODS: Fifteen consecutive patients undergoing endomyocardial biopsy (EMB) for suspected CA (median age 75 years, 1st-3rd quartiles 64-78 years], 67% male) were enrolled in an observational prospective study. Each patient underwent RV high-density EVM using a multipolar catheter and EMB. The primary outcome was death or heart failure hospitalisation at 1-year follow-up. We recorded electrographic features at EMB sampling sites and electroanatomic data in the overall RV, and explored their correlations with histopathologic findings and primary outcomes events. RESULTS: A final EMB-proven diagnosis of immunoglobulin light chain or transthyretin CA was formulated in 6 and 9 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.55 ± 0.44 mV and 5.14 ± 1.50 mV, respectively, in the overall RV, with lower values in AL CA patients. We found a significant inverse correlation between both bipolar and unipolar electrogram amplitude and amyloid burden according to EMB (P = 0.001 and P = 0.025, respectively). At 1-year follow-up, 7 patients (47%) experienced a primary outcome event; the extent of bipolar dense scar area at RV EVM was an independent predictor of primary outcome events at multivariable analysis (odds ratio 2.40; P = 0.037). CONCLUSIONS: In CA, electrogram amplitudes are around the lower limit of normal yet disproportionately low compared with the increased wall thickness. Out data suggest that RV electrogram amplitude may be a quantitative marker of amyloid burden, and that RV EVM may have prognostic value.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Electrophysiology fellowship experience and requirements: an EHRA survey.

AIMS: This study aims to survey current educational experience and the individual requirements for electrophysiologists in training. METHODS AND RESULTS: The European Heart Rhythm Association (EHRA) e-Communication Committee and the Scientific Initiatives Committee prepared a questionnaire and distributed it via newsletters, Twitter, LinkedIn, and Facebook. The survey consisted of 22 questions collected on an individual basis anonymously. Two hundred and forty-three responders from 35 countries (32% female, age 38 ± 6 years old) completed the survey. This EHRA electrophysiology (EP) fellowship survey showed that (i) hands-on participation and observation of EP procedures are very important; (ii) the main motivations to choose the EP fellowship institution are centre reputation and volume as well as the availability of a structured EP fellowship programme; (iii) 59% passed the EHRA exam and 46% took a national certification exam; (iv) respondents are overall satisfied with their own fellowships, but there are areas of less confidence such as conduction system pacing implantation and cardiac resynchronization therapy implantation; (v) 78% of respondents performed research during their fellowship, (vi) the optimal duration of an EP fellowship should be at least 2 years; and (viii) doing fellowships abroad is beneficial, but significant obstacles exist. CONCLUSION: The results of this EHRA survey may help to refine current EP fellowship programmes to improve the quality of EP training and early career building of young electrophysiologists.

Non-B DNA structures as a booster of genome instability.

Non-canonical secondary structures (NCSs) are alternative nucleic acid structures that differ from the canonical B-DNA conformation. NCSs often occur in repetitive DNA sequences and can adopt different conformations depending on the sequence. The majority of these structures form in the context of physiological processes, such as transcription-associated R-loops, G4s, as well as hairpins and slipped-strand DNA, whose formation can be dependent on DNA replication. It is therefore not surprising that NCSs play important roles in the regulation of key biological processes. In the last years, increasing published data have supported their biological role thanks to genome-wide studies and the development of bioinformatic prediction tools. Data have also highlighted the pathological role of these secondary structures. Indeed, the alteration or stabilization of NCSs can cause the impairment of transcription and DNA replication, modification in chromatin structure and DNA damage. These events lead to a wide range of recombination events, deletions, mutations and chromosomal aberrations, well-known hallmarks of genome instability which are strongly associated with human diseases. In this review, we summarize molecular processes through which NCSs trigger genome instability, with a focus on G-quadruplex, i-motif, R-loop, Z-DNA, hairpin, cruciform and multi-stranded structures known as triplexes.

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.

Anti-arrhythmic drugs in atrial fibrillation: tailor-made treatments.

During the last decades, many improvements have been made regarding the treatment of atrial fibrillation in terms of risk prevention, anti-coagulation strategies, and gain in quality of life. Among those, anti-arrhythmic drugs (AADs) have progressively fallen behind and overtaken by technological aspects as devices as procedures are now the standards of care for many patients. But is this it? Are AADs doomed to be relegated to an obscure and rarely read paragraph of the European recommendations? Or could they be still employed safely and effectively? In the present paper, we will discuss contemporary evidence in order to define where AADs still play a pivotal role, how should AADs be used, and whether a tailored approach can be the way to propose the right treatment to the right patient.

Data processing pipeline for cardiogenic shock prediction using machine learning.

Introduction: Recent advances in machine learning provide new possibilities to process and analyse observational patient data to predict patient outcomes. In this paper, we introduce a data processing pipeline for cardiogenic shock (CS) prediction from the MIMIC III database of intensive cardiac care unit patients with acute coronary syndrome. The ability to identify high-risk patients could possibly allow taking pre-emptive measures and thus prevent the development of CS. Methods: We mainly focus on techniques for the imputation of missing data by generating a pipeline for imputation and comparing the performance of various multivariate imputation algorithms, including k-nearest neighbours, two singular value decomposition (SVD)-based methods, and Multiple Imputation by Chained Equations. After imputation, we select the final subjects and variables from the imputed dataset and showcase the performance of the gradient-boosted framework that uses a tree-based classifier for cardiogenic shock prediction. Results: We achieved good classification performance thanks to data cleaning and imputation (cross-validated mean area under the curve 0.805) without hyperparameter optimization. Conclusion: We believe our pre-processing pipeline would prove helpful also for other classification and regression experiments.

Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study.

AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.