bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinterpretation of variant of unknown significance in the clinical setting of inherited cardiac conditions
Authors: Novelli V , Manzoni M , Sommariva E , Colombo G , Biondi M L , Mushtaq S , Farina S , Roberto M , Pizzamiglio F , Casella M , Pompilio G 
Published: October 2022

Abstract

Introduction
In the last years, genetic testing for inherited cardiac conditions (ICCs) is expanded and evolved at an incredible rate. This tool may inform treatment options and lifestyle choices to avoid arrhythmia triggers. Furthermore, identifying the genetic underpinning of the disorder improves risk assessment for asymptomatic or pre-symptomatic family members.
However, despite the large numbers of disease-causative genes identified in the last years, only 60% of the patients with a clinical diagnosis of ICCs carry a pathogenic or likely pathogenic variant. The remaining 40% of the cases have an inconclusive or ambiguous test caused by negative results or mainly by the identification of one or more variants of unknown significance (VUS). In this case, the test results are uninformative and clinically irrelevant, increasing uncertainty about medical management.

Purpose
We investigated whether a periodic re-evaluation of the detected VUS, using the American College of Medical Genetics and Genomics (ACMG) criteria, may impact the clinical setting of patients with suspected ICC and their family members.

Methods
We reevaluated 306 consecutive probands with suspected ICC undergoing genetic testing by next-generation sequencing using the Illumina TruSight Cardio Sequencing panel, from 2017 to 2021.

Results
Thirty-five percent of patients carried at least one variant in a gene associated with the phenotype. Of these, 94 had been previously classified as VUS and were not considered clinically actionable. After an average time of 36 months, they were reevaluated and 26.6% of the VUS were reclassified. In particular, 1 was downgraded to Benign and 24 were upgraded to Likely Pathogenic (16) or Pathogenic (8). According to the different phenotypes, the reclassification rate was 45.8% in Hypertrophic cardiomyopathy, 33.3% in Dilated cardiomyopathy, 27.3% in Arrhythmogenic cardiomyopathy, 12.5% in Brugada syndrome, and 50% in Long QT syndrome patients. This reclassification process allowed to recategorize 24 probands as clinically and molecularly diagnosed and to extend the genetic screening to their at-risk family members.

Conclusions
Given the extent of the clinical impact that genetic testing can have, these findings suggest that a periodic reevaluation of genetic test results, particularly VUS, should be a mandatory step in the ICC diagnostic workflow.

Funding Acknowledgement
Type of funding sources: None.
Characteristics and prognosis of the catecholamine induced QT prolongation syndrome
Authors: Gourraud J , Le Diffon T , Mansourati J , Clementy N , Thollet A , Rajalu A , Cotard V , Kyndt F , Martins R , Sacher F , Probst V 
Published: October 2022

Abstract

Background
We have recently demonstrated association of unexplained sudden cardiac arrest (SCA) with inheritance of catecholamine induced QT prolongation (CIQTP).

Objective
We here aim to describe incidence, characteristics and prognosis of this new syndrome in young patients with unexplained SCA or their relatives.

Methods
We reviewed the medical screening of all consecutive patients or their first-degree relatives explore from 2015 after the occurrence of a SCA before age 45. Structural heart disease or inherited arrhythmia diseases were excluded. A mental stress test was performed, as previously described, for each family members. All families with a positive mental stress were included in the study. Genetic screening was performed in at least one positive patient per family using targeted sequencing on a panel of 109 genes associated with inherited arrhythmias and cardiomyopathies.

Results
Among 456 patients screened (24 after SCA, 432 for familial screening) of 153 families, we identified 10 families (6.5%) with a catecholamine induced QT prolongation. No mutation was identified in these families. One hundred and ten patients were screened in CIQTP families. Thirty-four patients (30.9%) presented a CIQTP (mean age 42±20 yo, 64.7% of women). Five (14.7%) patients presented with previous symptoms (including 4 syncope and 1 SCA).
Two patients (5.9%) were implanted with an ICD and eleven (32.3%) were treated with beta blocker therapy mainly because of QT prolongation &gt;500 ms after mental stress test or previous symptoms.
After a 3.6±1.8 years of follow up, no sudden cardiac death nor syncope occurred on beta blocker therapy except for one patient implanted with an ICD after a SCA. Under beta blocker treatment the patient was asymptomatic for 5 years. After a suddenly stop of the beta blocker treatment, the patient underwent VF. For 3 years now the patient is asymptomatic under beta blocker treatment.

Conclusions
In our experience, CIQTP families represent 6.5% of cases of unexplained SCD and suggest systematic screening with a mental stress test for family screening after the occurrence of a SCA. Beta blocker therapy is very efficient to reduce the risk of SCA.

Funding Acknowledgement
Type of funding sources: None.
Temporal trends in incidence, patient characteristics, microbiology and in-hospital mortality in patients with infective endocarditis: a contemporary analysis of 86,469 cases between 2007 and 2019
Authors: Becher P M , Gossling A , Fluschnik N , Schrage B , Seiffert M , Schofer N , Blankenberg S , Kirchhof P M , Westermann D , Kalbacher D 
Published: October 2022

Abstract

Background
Infective endocarditis (IE) is characterized by high morbidity and mortality rates, despite recent improvements in diagnostics and treatment. We aimed to investigate incidence, clinical characteristics, and in-hospital mortality in a large-scale nationwide cohort.

Methods
Using data from the German Federal Bureau of Statistics, all IE cases in Germany between 2007 to 2019 were analyzed. Logistic regression models were fitted to assess associations between clinical factors and in-hospital mortality.

Results
In total, 86,469 patients were hospitalized with IE between 2007 and 2019. The mean age was 66.5±14.7 years and 31.8% (n=27,534/86,469) were female. Cardiovascular (CV) comorbidities were common. The incidence of IE in the German population increased from 6.3/100,000 to 10.2/100,000 between 2007 and 2019 (Figure 1). Staphylococcus (n=17,673/86,469; 20.4%) and streptococcus (n=17,618/86,469; 20.4%) were the most common IE-causing bacteria. The prevalence of staphylococcus gradually increased over time, whereas blood culture-negative IE (BCNIE) cases decreased (Figure 2). In-hospital mortality in patients with IE was 14.9%. Compared to BCNIE, staphylococcus and gram-negative pathogens were associated with higher in-hospital mortality. In multivariable analysis, factors associated with higher likelihood of in-hospital mortality were advanced age, female sex, CV comorbidities (e.g., heart failure, COPD, diabetes, stroke), need for dialysis or invasive ventilation, and sepsis.

Conclusions
In this contemporary cohort, incidence of IE increased over time and in-hospital mortality remained high (∼15%). While staphylococcus and streptococcus were the predominant microorganisms, bacteremia with staphylococcusand gram-negative pathogens were associated with higher likelihood of in-hospital mortality. Our results highlight the need for new preventive strategies and interventions in patients with IE.

Funding Acknowledgement
Type of funding sources: None.
Long-term clinical course and prognostic factors of heart failure with reduced ejection fraction (HFrEF) patients underwent primary prophylactic implantable cardioverter defibrillator (ICD)
Authors: Sugawara M , Kondo Y , Yoshino Y , Ryuzaki S , Chiba T , Kitagawa M , Ito R , Nakano M I , Kajiyama T , Nakano M A , Kobayashi Y 
Published: October 2022

Abstract

Background
For decades, ICD is a well-established therapy for improving prognosis of structural heart disease with severe cardiac dysfunction, and ICD for primary prophylaxis against sudden cardiac death were routinely provided. However, long-term prognosis and clinical course are different in each individual patient with an ICD, and it is moreover unclear what kind of factors might have influences on their clinical outcomes.

Purpose
The aim of this study is to clarify long-term prognosis and predictors of future major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis in Japanese population.

Methods
We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2006 to 2020 at our institute and met the criteria of ICD recommendation of the latest Japanese guideline. Its requirements are receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). Additionally, prior NSVT is considered Class I ICD recommendation. In the case of ischemic cardiomyopathy (ICM), ICD implantation was done at least 40 days after myocardial infarction and at least 90 days after revascularization. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies.

Results
A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). One hundred twenty patients (81%) were programmed with a shock-only zone over 200 beats per minute. The median follow-up duration was 58.5 months. Among those 148 patients, MACEs were occurred to 60 patients (41%). As a result of dividing all patients into two groups by the occurrence of MACE, LVEF and LVDd were worse in MACE(+) group, whereas, MACE(−) had greater number of co morbidities. The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03–1.12, p&lt;0.001), AF (HR: 2.88, 95% CI: 1.56–5.31, p&lt;0.001) and ICM (HR: 1.78, 95% CI: 1.00–3.16, p=0.049) were the independent predictors of MACEs (Table). However, initial ICD programming was not related to the occurrence of MACE.

Conclusions
The incidence of MACEs in patients with an ICD and severe HFrEF was substantially high in this Japanese population. Etiology of ICM, left ventricle size, and AF were the potential risk factors for future MACEs.

Funding Acknowledgement
Type of funding sources: None.
Other rhythm abnormalities found in 10,593 patients with paroxysmal atrial fibrillation over a 14-day ambulatory ECG monitoring period
Authors: Bardy G , Wang M , Boleyn R , McLendon K 
Published: October 2022

Abstract

Background
The incidence of other arrhythmias in patients with Paroxysmal Atrial Fibrillation (PAF) can affect choice of subsequent diagnostic procedures as well as drug, implanted device and ablation management. In the endless stream of new ECG monitoring technologies, whose primary focus sits on AF identification, other arrhythmias can be minimized in their importance. And yet, in patients with PAF, management is often altered by the presence of both significant and even subtle additional concomitant rhythm abnormalities. Clinically meaningful non-PAF rhythms may not be reliably captured by most cardiac ambulatory ECG monitors, especially those focusing purely on AF.

Purpose
The objective of this study was to identify the extent and types of other unique rhythm abnormalities that might influence management in patients found to have PAF on a routine outpatient ambulatory ECG.

Methods
A total of 10,593 pts wearing an ambulatory ECG monitor had PAF. Monitors were ordered for standard clinical indications predominantly by their managing cardiologists. Patient ECG data was interpreted by 3 serial readers clinically informed on electrophysiological principles of arrhythmia diagnostics. Concomitant rhythm disorders, as manifested on the surface ECG monitor, were then quantified as a percentage of the PAF study population. Patients with chronic AF were excluded from this analysis.

Results
The primary results are summarized in Figure 1. Of 10,593 pts with PAF, only 391 (4%) were found to have only PAF and no other rhythm abnormalities. At least 1 additional rhythm abnormality was found in 96% and 2-to-8 additional rhythm disorders were present in 68% of patients.

Conclusion
Nearly all patients with PAF have additional rhythm abnormalities that can only be identified using a cardiac monitor with high P-wave fidelity. Even modest, and certainly serious, additional ECG rhythm abnormalities can alter physician management of PAF as pertains to selection of additional diagnostic testing, drug choice, device selection, and/or ablation specifics. Simplistic and/or commercial grade ECG monitors cannot provide such detail and carry the risk of misdirecting patient management.

Funding Acknowledgement
Type of funding sources: None.
Various arrhythmia types and their day-by-day occurrence rates over a 14-day period using a P-wave sensitive ambulatory ECG monitored population
Authors: Bardy G , Wang M , Boleyn R , McLendon K 
Published: October 2022

Abstract

Background
Many studies on ECG monitoring and arrhythmia detection use the term “diagnostic yield”, a vague term and one without the type of diagnostic precision that cardiologists value. Moreover, diagnostic yield of specific arrhythmias is not well understood on a day-by-day basis.

Purpose
We used a continuous 14-day ECG monitor to record the incremental occurrence of a broad variety of specific arrhythmias each day from a general outpatient population suspected of having an arrhythmia.

Methods
A total of 546 patients were monitored for 14±1 day in the absence of artifact that would otherwise obscure the rhythm. Without such stipulations, arrhythmias could not be truly categorized as a function of time. Patients were randomly selected who satisfied the aforementioned criteria. The studies were prescribed by the patient's managing physician for standard clinical indications, and they spanned across 237 distinct institutions. The recordings were interpreted by 3 serial readers clinically knowledgeable on electrophysiological principles of arrhythmia diagnostics. All reports were then confirmed in their entirety by a cardiac electrophysiologist. The daily diagnostic rate for specific arrhythmia occurrence was then tabulated. Of note, algorithmic and AI diagnostic approaches were not relied upon for arrhythmia diagnoses.

Results
Select arrhythmia/conduction abnormalities are shown in the attached Figure, demonstrating different arrhythmias manifesting at different rates. In 61% of pts, at least one rhythm disorder was found that could affect patient management over 14 days. In 28% of pts, two disorders were found while 12% had three or more disorders. P-wave specificity on the ECG aided in identifying 67.9% of those unique arrhythmias. When more than one arrhythmia type was identified, they typically occurred on different days. In contrast, the standard 1-day report, if implemented, would have diagnosed only 20% of patients and rarely would have found multiple rhythm abnormalities

Conclusion
Different arrhythmia categories manifest at different rates on a 14-day continuous ECG. Clinical abnormalities in rhythm and/or conduction occur in 61% of patients randomly selected from a broad array of institutions. Moreover, 28% had 2 disorders and 12% had &gt;3 disorders, usually occurring on different days. Lastly, 67.9% of rhythms were identified due to a high fidelity P-wave ECG signal. These findings suggest that a 14-day P-wave sensitive ECG recording has substantive diagnostic value even if a suspected arrhythmia were to occur on day 1. Further, ECG recordings of 1 day (i.e., standard Holter monitor duration) severely diminish diagnostic value and should be avoided.

Funding Acknowledgement
Type of funding sources: None.
Transformation of computerized electrocardiogram data into novel means to differentiate wide complex tachycardias
Authors: Katbamna B , Kashou A H , Shaikh P , Lococo S , Cooper D , Cuculich P , Asirvatham S , Noseworthy P , Desimone C , May A 
Published: October 2022

Abstract

Background
Accurate automated wide QRS complex tachycardia (WCT) discrimination between ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) can be accomplished using novel calculations derived from computerized electrocardiogram (ECG) data from paired WCT and baseline ECGs.

Purpose
Our aim was to develop and trial novel WCT discrimination approaches for WCT patients with and without a corresponding baseline ECG. Central to this analysis was the creation and use of a novel parameter (i.e., percent monophasic time-voltage area [PMonoTVA] [%]) that may be derived from computerized ECG measurements present on the WCT ECG alone.

Methods
In a two-part study, we derived and tested WCT differentiation models comprised of novel and previously established parameters formulated from computerized data of paired WCT and baseline ECGs. In Part 1, novel and established parameters generated from WCT and baseline ECG data were used to derive, validate, and compare five different binary classification models: (i) logistic regression [LR], (ii) artificial neural network [ANN], (iii) Random Forests [RF], (iv) support vector machine [SVM], and (v) ensemble learning (EL). In Part 2, two unique LR models were derived, validated, and compared using parameters generated from computerized data of the (i) WCT ECG alone (i.e., Solo Model) and (ii) paired WCT and baseline ECGs (i.e., Paired Model).

Results
In Part 1, among 103 patients with VT or SWCT diagnoses established from corroborating electrophysiology studies or intra-cardiac device recordings, favorable diagnostic performance was achieved by all modeling technique subtypes: LR (area under the receiver operating characteristic curve [AUC] 0.95), ANN (AUC 0.91), RF (AUC 0.97), SVM (AUC 0.98), and EL (AUC 0.97). In Part 2, among 235 patients with a VT or SWCT diagnosis established with (Gold Standard cohort) or without (Non-Gold Standard cohort) a corroborating electrophysiology procedure or intra-cardiac device recording, favorable diagnostic performance was achieved by the Solo Model (AUC 0.86) and Paired Model (AUC 0.95) (Table).

Conclusion
Accurate WCT discrimination may be accomplished using novel parameters derived from computerized data of the WCT ECG alone and paired WCT and baseline ECGs.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health
Morphology-Voltage-P-wave duration (MVP) score in prediction of incident atrial fibrillation in an elderly epidemiologic cohort
Authors: Baturova M A , Cornefjord G , Carlson J C , Johnson L S B , Smith J G , Platonov P 
Published: October 2022

Abstract

Background
Interatrial block (IAB) on electrocardiography (ECG) and reduced P wave voltage reflect atrial abnormalities which may contribute to development of atrial fibrillation (AF).

Purpose
We aimed to assess the value of a recently proposed ECG risk score that combines the morphology, voltage and length of the P wave (MVP score) for prediction of incident AF in a prospective population-based setting.

Material and methods
The study population is based on the large, prospective Malmö Preventative Project (MPP) cohort. We included subjects without a history of AF, with a readable ECG in sinus rhythm and an echocardiography performed in 2002–2006 (n=983, mean age 70±5 years, 38% females). Median follow-up was 4.2 (IQR 3.7–4.8) years. ECGs were digitally processed using the Glasgow algorithm. Advanced IAB (aIAB) was defined as a P-wave ≥120 ms and biphasic morphology (+/−) in inferior leads, partial IAB (pIAB) as P-wave ≥120 ms and a monophasic positive morphoology in inferior leads. MVP score was calculated based on the P-wave morphology in inferior leads, voltage in lead 1, and P-wave duration (Table 1).Incident AF events (n=66, 7%) were obtained from the Swedish Hospital Discharge Register and Cause of Death Register. Cox regression analysis and Kaplan Meier curve analysis were used to study the association of echocardiographic and P-wave characteristics with the risk of new onset AF.

Results
At baseline the mean MVP score was 1±1, none of the subjects had MVP score above 4. MVP score correlated with left atrial (LA) area: Pearson r=0.192, p&lt;0.001. After adjustment for age, gender and LA enlargement expressed as LA area &gt;20 cm2, new onset AF was associated with MVP score 4 (HR 6.17, 95% CI 1.76–21.64 compared to those with MVP score &lt;4, Figure 1). Neither aIAB (univariate HR 1.93 CI 95% 0.82–4.56), nor pIAB (univariate HR 1.16 CI 95% 0.52–2.55) predicted incident AF.

Conclusion
In a population-based elderly epidemiological cohort, the ECG-based MVP score was significantly associated with incident AF, independently of LA enlargement.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Swedish Heart-Lung Foundation
Cardiac dysrhythmias among coronavirus-19 recovered symptomatic patients
Authors: Shamia D , Tsaban G , Baham L , Raviv Y , Haim M 
Published: October 2022

Abstract

Background
The coronavirus (COVID-19) pandemic, which affected millions of people worldwide, is associated with a chronic fatigue sequela, also known as long-COVID. While various adverse effects of COVID-19 on the cardiovascular system were reported, the prolonged sequela of COVID-19 on heart rhythm remains unknown.

Aim
To describe the prevalence of cardiac dysrhythmias among patients who presented with Long Covid following recovery from COVID-19 infection.

Methods
We conducted a prospective study among 87 patients who suffered from Long Covid syndrome following recovery from COVID-19 and were treated in the COVID-19 recovery clinic between December 2020 and June 2021. All patients were referred for transthoracic echocardiography (TTE) and 24-hour Holter examination.

Results
The mean age was 52+13 years, and 52 (59.8%) patients were females. Seventy-nine (90.8%) of the patients had normal sinus rhythm without evidence of any arrhythmias. Atrial premature beats were recorded in 70 (80.5%) patients with a median of 6/day (interquartile range 3–20/day; maximum: 5180/day). Ventricular premature beats were recorded in 50 (57.5%) patients with a median of 4/day (interquartile range 2–19/day; maximum: 6847/day). Overall, seven patients (8%) had sustained atrial dysrhythmias: one had atrial fibrillation, one had atrial flutter, and five had atrial tachycardia. Sixty-six (75.9%) patients underwent TTE, which was mainly unremarkable as 65 patients had a normal left ventricular function, and three (4.5%) patients had evidence of pulmonary hypertension.

Discussion
Cardiac arrhythmias are not uncommon among symptomatic COVID-19 recovered patients. Atrial arrhythmias were most common, with an up to 8% incidence rate. These findings may suggest that atrial dysrhythmias may be associated with long-term symptomatic sequela of COVID-19 infection.

Funding Acknowledgement
Type of funding sources: None.