Arrhythmogenic Left Ventricular Cardiomyopathy: From Diagnosis to Risk Management.

PURPOSE OF REVIEW: Left ventricular arrhythmogenic cardiomyopathy (ALVC) is a rare and poorly characterized cardiomyopathy that has recently been reclassified in the group of non-dilated left ventricular cardiomyopathies. This review aims to summarize the background, diagnosis, and sudden cardiac death risk in patients presenting this cardiomyopathy. RECENT FINDINGS: Although there is currently a lack of data on this condition, arrhythmogenic left ventricular dysplasia can be considered a specific disease of the left ventricle (LV). We have collected the latest evidence about the management and the risks associated with this cardiomyopathy. SUMMARY: Left ventricular arrhythmogenic cardiomyopathy is still poorly characterized. ALVC is characterized by fibrofatty replacement in the left ventricular myocardium, with variable phenotypic expression. Diagnosis is based on a multiparametric approach, including cardiac magnetic resonance (CMR) and genetic testing, and is important for sudden cardiac death (SCD) risk stratification and management. Recent guidelines have improved the management of left ventricular arrhythmogenic cardiomyopathy. Further studies are necessary to improve knowledge of this cardiomyopathy.

Predictors of Plasma Levels of Direct Oral Anticoagulants Among Patients with Atrial Fibrillation in Need of Elective Cardiac Procedures.

BACKGROUND: The withdrawal timing of direct oral anticoagulants (DOACs) among patients in need of elective invasive surgery is based on DOAC pharmacokinetics in order to perform the procedure out of the DOAC peak plasma concentration. We aimed to investigate the prevalence and predictors of plasma levels of DOACs out of trough range in patients with atrial fibrillation (AF) in need of elective cardiac procedure. MATERIALS AND METHODS: We evaluated all consecutive AF patients on DOAC therapy in need of elective cardiac procedure, admitted to our division from January 2022 to March 2022. All patients underwent DOAC plasma dosing the morning of procedure day. They were categorized as in range, above range, and below range, according to the DOAC reference range at the downstream point. The timing of discontinuation of DOAC therapy was considered as appropriate or not, according to the current recommendations. The clinical predictors of out-of-range DOAC plasma levels have been evaluated. RESULTS: We included 90 consecutive AF patients (56.6% male, mean age 72.95 ± 10.12 years); 74 patients (82.22%) showed DOAC concentration out of the expected reference range. In half of them (n, 37), the DOAC plasma concentration was below the trough reference range. Of the study population, 17.7% received inappropriate DOAC dosages (10% overdosing, 7% underdosing), and 35.5% had incorrect timing of DOAC withdrawal (26% prolonged, 9.5% shortened). At multivariable analysis, inappropriate longer DOAC withdrawal period (OR 10.13; P ≤ 0.0001) and increased creatinine clearance (OR 1.01; P = 0.0095) were the independent predictors of plasma DOAC levels below the therapeutic trough range. In contrast, diabetes mellitus (OR 4.57; P = 0.001) was the only independent predictor of DOAC plasma level above the therapeutic trough range. CONCLUSION: Increased creatinine clearance and inappropriate longer drug withdrawal period are the only independent predictors of DOAC plasma levels below the reference range; in contrast, diabetes is significantly correlated with DOAC plasma levels above the reference.

Biodistribution Assessment of a Novel 68Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis.

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

Implantable loop recorders in patients with Brugada syndrome: the BruLoop study.

BACKGROUND AND AIMS: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. METHODS: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. RESULTS: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs. CONCLUSIONS: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.

Asystole on loop recorder in patients with unexplained syncope and negative tilt testing: age distribution and clinical predictors.

BACKGROUND: Approximately 50% of patients with unexplained syncope and negative head-up tilt test (HUTT) who have an electrocardiogram (ECG) documentation of spontaneous syncope during implantable loop recorder (ILR) show an asystolic pause at the time of the event. OBJECTIVE: The aim of the study was to evaluate the age distribution and clinical predictors of asystolic syncope detected by ILR in patients with unexplained syncope and negative HUTT. METHODS: This research employed a retrospective, single-center study of consecutive patients. The ILR-documented spontaneous syncope was classified according to the International Study on Syncope of Uncertain Etiology (ISSUE) classification. RESULTS: Among 113 patients (54.0 ± 19.6 years; 46% male), 49 had an ECG-documented recurrence of syncope during the observation period and 28 of these later (24.8%, corresponding to 57.1% of the patients with a diagnostic event) had a diagnosis of asystolic syncope at ILR: type 1A was present in 24 (85.7%), type 1B in 1 (3.6%), and type 1C in 3 (10.7%) patients. The age distribution of asystolic syncope was bimodal, with a peak at age < 19 years and a second peak at the age of 60-79 years. At Cox multivariable analysis, syncope without prodromes (OR 3.7; p = 0.0008) and use of beta blockers (OR 3.2; p = 0.002) were independently associated to ILR-detected asystole. CONCLUSIONS: In patients with unexplained syncope and negative HUTT, the age distribution of asystolic syncope detected by ILR is bimodal, suggesting a different mechanism responsible for asystole in both younger and older patients. The absence of prodromes and the use of beta blockers are independent predictors of ILR-detected asystole.

Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope.

AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1-0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.

Comprehensive Cardiovascular Management of Myotonic Dystrophy Type 1 Patients: A Report from the Italian Neuro-Cardiology Network.

Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network-"Rete delle Neurocardiologie" (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of myotonic dystrophy type 1 (MD1).

Implantable cardiac monitors: artificial intelligence and signal processing reduce remote ECG review workload and preserve arrhythmia detection sensitivity.

Introduction: Implantable cardiac monitors (ICMs) provide long-term arrhythmia monitoring, but high rates of false detections increase the review burden. The new "SmartECG" algorithm filters false detections. Using large real-world data sets, we aimed to quantify the reduction in workload and any loss in sensitivity from this new algorithm. Methods: Patients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as "true" or "false." We quantified the relative reduction in workload assuming "false" sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians. Results: Of our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as "false," reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers inspected on average 105 sECGs per working hour. This results in an annual working time per patient of 83 min without SmartECG, and 48 min with SmartECG. The loss of sensitivity is estimated as 2.6%. In the majority of cases where true arrhythmias were rejected, SmartECG classified the same type of arrhythmia as "true" before or within 3 days of the falsely rejected sECG. Conclusion: SmartECG increases efficiency in long-term arrhythmia monitoring using ICMs. The reduction of workload by SmartECG is meaningful and the risk of missing a relevant arrhythmia due to incorrect filtering by the algorithm is limited.

False-positive alarms in patients with implantable loop recorder followed by remote monitoring: A systematic review.

Remote Monitoring (RM) has been shown to provide useful information about arrhythmic events in patients with implantable loop recorders (ILRs), however there is few and conflicting data about the false positive (FP) alarms burden and characteristics among ILR recipients. The aim of the present systematic review was to evaluate incidence and characteristics of FP alarms among ILR patients followed by RM. We developed a systematic research in Embase, MEDLINE and PubMed databases and selected all papers focused on false positive ILR transmissions published from June 1, 2013 to June 1, 2023. Case reports, meeting summaries, posters and simple reviews were excluded. Twelve reports were finally selected, including five prospective and seven retrospective studies. Information about population characteristics, device type and setting, overall transmissions and FP alarms and any adopted strategies to reduce them were extracted from an overall population of 3.305 patients. FP alarms were 59.7% of the overall remote transmissions and were found in 1/5 of the analyzed population. FP alarms for atrial fibrillation were the most common cause of false transmissions and were mainly due to premature atrial and ventricular complexes. No clinical predictors of FP alarms were identified, except for nonparasternal ILR implantation site. Since the overload work due to FP alarms might reduce the benefit of remote monitoring of ILR patients, the device optimization is an important step until an help from machine-learning algorithms is available.

The Rate of Asystolic Reflex Syncope Is Not Influenced by Age.

BACKGROUND: The head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. OBJECTIVES: The main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). METHOD: We performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. RESULTS: A total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). CONCLUSIONS: The rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.

Update on the Pharmacological Actions of Enoxaparin in Nonsurgical Patients.

Low-molecular-weight heparins are a class of drugs derived from the enzymatic depolymerization of unfractionated heparin that includes enoxaparin. Several studies have been performed on enoxaparin in recent years, in particular for the prevention and treatment of venous thromboembolism and for the treatment of acute coronary syndrome. Furthermore, the use of enoxaparin has been extended to other clinical situations that require antithrombotic pharmacological prevention, such as hemodialysis and recurrent abortion. In this review, we report the main clinical experiences of using enoxaparin in the prevention of VTE in nonsurgical patients.

Pre-TAVI imaging: an Italian survey by the CT PRotocol optimization (CT-PRO) group.

PURPOSE: The purpose of this survey was to evaluate the current state-of-art of pre-TAVI imaging in a large radiological professional community. METHODS: Between December 2022 and January 2023 all members of the Italian Society of Medical and Interventional Radiology (SIRM) were invited by the CT PRotocol Optimization group (CT-PRO group) to complete an online 24-item questionnaire about pre-TAVI imaging. RESULTS: 557 SIRM members participated in the survey. The greatest part of respondents were consultant radiologists employed in public hospitals and 84% claimed to routinely perform pre-TAVI imaging at their institutions. The most widespread acquisition protocol consisted of an ECG-gated CT angiography (CTA) scan of the aortic root and heart followed by a non-ECG-synchronized CTA of the thorax, abdomen, and pelvis. Contrast agent administration was generally tailored on the patient's body weight with a preference for using high concentration contrast media. The reports were commonly written by radiologists with expertise in cardiovascular imaging, and included all the measurements suggested by current guidelines for adequate pre-procedural planning. About 60% of the subjects affirmed that the Heart Team is present at their institutions, however only 7% of the respondents regularly attended the multidisciplinary meetings. CONCLUSIONS: This survey defines the current pre-TAVI imaging practice in a large radiological professional community. Interestingly, despite the majority of radiologists follow the current guidelines regarding acquisition and reporting of pre-TAVI imaging studies, there is still a noteworthy absence from multidisciplinary meetings and from the Heart Team.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

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.

Bone marrow metastases: a systematic review of a neglected involvement in malignant melanoma.

The occurrence of bone marrow metastases (BMM) in melanoma patients is often underestimated, with only 7% detected during in-vivo staging procedures but rising to 45% in autopsy cases. This systematic review aims to shed light on the clinical and laboratory features of BMM in melanoma by analyzing 73 studies selected from 2 482 initially retrieved from PubMed, Embase , and Cochrane CENTRAL databases. Our findings reveal a slight male predominance, with a median age at BMM diagnosis of 56 years. Primary melanoma sites included the skin (52%), mucosa (8.8%), uvea (20.5%) and unidentified (19%). BMM was preceded by lymph node involvement in 36.5% of cases, whereas 63% showed no nodal metastases, with direct BMM occurring in 22.5% and metastases to other sites in 41%. Common BMM symptoms included pain (60.7%), anemia (80%), thrombocytopenia, leukoerythroblastosis, pancytopenia and leukopenia, while disseminated intravascular coagulation was detected in 11% of cases. In 23.6% of cases, BMM was amelanotic. The prognosis for BMM is grim, with a median survival of only 2 months. Conventional therapies for BMM remain largely ineffective, emphasizing the importance of considering bone marrow as a potential metastatic site in melanoma patients.

Efficient recycling pathway of bio-based composite polyurethane foams via sustainable diamine.

Aminolysis is widely recognized as a valuable chemical route for depolymerizing polymeric materials containing ester, amide, or urethane functional groups, including polyurethane foams. Bio-based polyurethane foams, pristine and reinforced with 40 wt% of sustainable fillers, were depolymerized in the presence of bio-derived butane-1,4-diamine, BDA. A process comparison was made using fossil-derived ethane-1,2-diamine, EDA, by varying amine/polyurethane ratio (F/A, 1:1 and 1:0.6). The obtained depolymerized systems were analyzed by FTIR and NMR characterizations to understand the effect of both diamines on the degradation pathway. The use of bio-based BDA seemed to be more effective with respect to conventional EDA, owing to its stronger basicity (and thus higher nucleophilicity), corresponding to faster depolymerization rates. BDA-based depolymerized systems were then employed to prepare second-generation bio-based composite polyurethane foams by partial replacement of isocyanate components (20 wt%). The morphological, mechanical, and thermal conductivity properties of the second-generation polyurethane foams were evaluated. The best performances (σ10 %=71 ± 9 kPa, λ = 0.042 ± 0.015 W∙ m-1 ∙K-1) were attained by employing the lowest F/A ratio (1:0.6); this demonstrates their potential application in different sectors such as packaging or construction, fulfilling the paradigm of the circular economy.