bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of immunosuppression in patients with lymphocytic myocarditis and myocardial parvovirus B19 with or without human herpesvirus 6 co-presence
Authors: Elsanhoury A , Kuehl U , Klingel K , Strueben A , Morris D , Van Linthout S , Tschoepe C 
Published: October 2022

Abstract

Background
Parvovirus B19 (B19V) and Human Herpesvirus 6 (HHV6) are commonly detected in endomyocardial biopsy (EMB) specimens of patients with myocarditis symptoms. Whether B19V- and HHV6-DNA belong to the cardiac bio-portfolio remains unclear [1,2]. Until today, the role of B19V-/HHV6-DNA presence in myocarditis is doubtful. Both viruses have been detected in the myocardium, even independent of cardiac inflammation. Yet, their contribution to myocarditis remains controversial. The European Society of Cardiology guidelines exclude the use of immunosuppression in patients with virus-associated myocarditis [3]. Whether myocarditis patients with the presence of B19V-DNA alone or with HHV6-DNA in EMB findings can be treated using immunosuppression, remains a delicate question for clinicians.

Methods
931 patients with unexplained heart failure symptoms underwent EMB investigation to determine the underlying cause. Patients with low-levels (&lt;1000 copies/μg DNA) of B19V-DNA and HHV6-DNA were identified. A sub-cohort of 28 patients who suffered from chronic-persistent lymphocytic myocarditis with ongoing symptoms was treated with azathioprine 100 mg once daily and prednisolone 1 mg/kg/day tapered down by 10 mg every two weeks followed by a second EMB. Twenty out of 28 patients had B19V-DNA only (mean LVEF=38%, age=47±15) and eight patients had B19V-/HHV6-DNA copresence (mean LVEF=39%, age=42±10). Patients with systemic infections were excluded. Both cohorts received standard heart failure medications. Continuous variables are expressed as mean±SD.

Results
B19V-DNA alone and in the presence of HHV6-DNA was detectable in the EMB of 377 and 63 patients, respectively. Following the immunosuppression course, the patients with B19V-DNA only and those with B19V-/HHV6-DNA showed complete resolution of inflammation in 12/20 and 5/8 patients, New York Heart Association (NYHA) functional class improvement in 9/20 and 4/8 patients, LVEF improvement by 8.0±13.8% (p&lt;0.05) and 8.4±9.6% (p&lt;0.05), and a reduction of LVEDD by 3.8±6.1mm (p&lt;0.05) and 1.0±7.7mm (p&gt;0.05), respectively. Importantly, following immunosuppression B19V and HHV6-DNA copy numbers went down from 186±266 to 130±186 copies/μg DNA and from 71±141 to 58±143 copies/μg DNA, respectively.

Conclusion
Chronic lymphocytic myocarditis patients with persistent B19V-DNA even in co-presence of HHV6-DNA may benefit from combined immunosuppression therapy. The therapy is clinically effective and safe to reduce cardiac inflammation independent of B19V- and HHV6-DNA copy numbers. In conclusion, we show for the first time that cases with chronic lymphocytic myocarditis can be principally treated with immunosuppression, despite B19V-/HHV6-DNA EMB presence.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Berlin Institute of Health-Center for Regenerative Therapies
Accuracy of ICD-10 codes for patients with acute myocarditis: a retrospective study at a large tertiary centre in London, UK
Authors: Roy R , Cannata A , Bhatti P , Daniel A , Rosmini S , Birkenshaw A , Rind I , Sado D , Piper S , Scott P , McDonagh T , Bromage D 
Published: October 2022

Abstract

Background
Acute myocarditis (AM) is an inflammatory disease of the myocardium that is associated with heterogenous clinical presentations, which may be non-specific. Furthermore, several cardiac diseases can mimic its clinical phenotype. Research in AM frequently utilises ICD-10 codes from hospital admissions for case identification. We retrospectively confirmed or refuted a diagnosis of AM according to ESC Position Statement criteria in patients with an ICD-10 code for AM.

Methods
We performed a single-centre retrospective analysis of all unique admissions with ICD-10 codes corresponding to myocarditis or myopericarditis in the first three coding positions at King's College Hospital, London, United Kingdom. The diagnosis was classified as “confirmed” if proven by cardiac magnetic resonance imaging (CMR) or endomyocardial biopsy (EMB) or “suspected” in the absence of CMR or EMB if other ESC Position Statement criteria were met. To identify additional cases, we used an open-source retrieval system for unstructured clinical data (CogStack). We searched hospital and Intensive Care Unit (ICU) discharge summaries for inpatients discharged alive containing the keywords “myocarditis” or “myopericarditis”. We also searched for patients who died during the study period where the keywords “myocarditis” or “myopericarditis” were included on the death notification.

Results
We identified 308 unique admissions with an ICD-10 code for myocarditis or myopericarditis in this study, presenting between 2008 and 2020 (Figure 1). Overall, 26.0% of patients (n=80/308) could be excluded from a diagnosis of AM on review of the clinical summary. A total of 16.2% of patients (n=50/308) had insufficient evidence of AM, 1.9% (n=6/308) had not had coronary artery disease excluded as a culprit for the presentation, and 10.1% (n=31/308) had an alternative diagnosis. Only 45.8% (n=141/308) of all patients met criteria for suspected or confirmed AM. Of those, 86.5% (n=122/141) of cases were confirmed by CMR. Overall, 39.6% of patients with an ICD-10 code indicating AM had a confirmed diagnosis. An additional 46 suspected and 197 confirmed cases were identified using open-source retrieval from unstructured clinical data.

Conclusion
AM has heterogenous and sometimes non-specific clinical presentations, which may be compounded by limited access to CMR and EMB. We identified significant misclassification using ICD-10 codes. It is crucial to ensure that studies investigating AM include only patients meeting appropriate diagnostic criteria, thereby ensuring a high-quality evidence base in this disease.

Funding Acknowledgement
Type of funding sources: None.
Long-term prognosis in left ventricular non-compaction cardiomyopathy
Authors: Guerra F , Barbarossa A , Alfieri M , Paolini F , Stronati G , Ciliberti G , Torselletti L , Coretti F , Coraducci F , Belleggia S , Principi S , Silenzi M , Manfredi R , Falanga U , Dello Russo A 
Published: October 2022

Abstract

Introduction
Left ventricular non compaction (LVNC) cardiomyopathy is an often underdiagnosed disease characterized by a thickened myocardium with a two-layered structure. Clinical presentations are very variable, ranging from an apparent lack of functional anomalies to heart failure, ventricular arrhythmias and, in some cases, even ischaemic stroke. Despite great improvements in diagnostic performance, there is still a wide lack of evidence regarding prognosis and management of affected patients.

Purpose
The aim of the present study was to investigate predictors of cardiovascular death or cardiovascular-related hospitalization in patients with LVNC over a long-term follow-up.

Methods
All consecutive patients with a definite diagnosis of LVNC admitted to the Cardiomyopathy Clinic of our institution from Jan 2015 to Dec 2020 were consecutively enrolled. Inclusion criteria were an age ≥18 years old and a diagnosis of LVNC made either by MRI or echocardiography. Exclusion criteria were a life expectancy ≤1 year and the inability to express informed consent for the study. All patients were follwed-up every six months. The primary endpoint was a composite of cardiovascular death and unplanned cardiovascular hospitalization.

Results
Twenty-one patients (14 male, age 40±17 years) meeting the inclusion criteria were prospectively enrolled and followed-up for a median of five years.
LVNC patients with a previous history of supraventricular tachycardia at the time of diagnosis are more likely to meet the primary composite endpoint during follow-up (60% vs. 18%; p=0.048; Figure 1). On the other hand, neither LVEF (measured either with echo or CMR) nor functional status were associated with a significantly increased risk of the composite endpoint (all p=NS). Other significant predictors of increased risk include history of OSAS (z2 = 4.158), active/previous smoking (z2 = 6.279), and ST-segment alterations (z2 = 4.158). NC/C, as measured by either echo or CMR, was not a predictor of cardiovascular events (HR 0.18; 95% CI 0.31–1.08; p=NS).

Conclusions
Our data show how, in patients with LVNC, supraventricular tachycardias are related to worse outcomes and their presence should prompt a closer follow-up in order to detect possible adverse events. ST-segment alterations, OSAS and smoking are also related to a poorer prognosis, but their relevance should be further assessed. Surprisingly, in our sample LVEF and NC/C ratio were not predictors of worse outcomes; the reason might be that in LVNC patients mortality and cardiovascular hospitalizations resemble complex genetic and molecular mechanisms that differentiate them from other cardiomyopathies, but the paucity of the population prevents us from making wider inferences.

Funding Acknowledgement
Type of funding sources: None.
Atrial fibrillation concerning worse prognosis in patients with left ventricular noncompaction
Authors: Xu W 
Published: October 2022

Abstract

Purpose
This study aims to investigate the relationship between atrial fibrillation (AF) and the prognosis of patients with left ventricular noncompaction (LVNC).

Methods
This retrospective study enrolled 302 patients (median age 46 years, 65.9% male) diagnosed as LVNC through echocardiography or cardiac nuclear magnetic according to Jenni criteria1 and Petersen criteria2, respectively. The primary endpoint is major cardiovascular adverse events (MACEs) which is a composite endpoint including heart transplantation, deaths in-hospital, stroke, system embolism, malignant ventricular arrhythmia, and rehospitalization for cardiovascular reasons. The second endpoints are thromboembolism events including system embolism and stroke.

Results
The patients with LVNC were divided into 2 groups: with AF group (n=56) and without AF group (n=246). In the group of patients combined with AF and LVNC, the proportion of CHA2DS2-VASc score≥2 was 66.07%. The rate of receiving oral anticoagulant therapy in LVNC patients with AF was significantly higher than without the AF group (69.64% vs. 19.51%, p&lt;0.01). After a median follow-up of 4.3 years, a total of 69 MACEs (22.85%) and 19 thromboembolism events (6.3%) occurred. Among them, 49 MACEs in the non-AF group (19.92%) while 20 cases (35.71%) occurred MACEs in the AF group (p=0.01). Moreover, the rate of thromboembolism in the AF group was notably higher compared with the non-AF group (16.1% vs. 4.1%, p=0.01). The Kaplan-Meier curves (Figure 1) compared by the log-rank test showed that the AF group was associated with a higher risk of thromboembolism events than the non-AF group and the difference between the 2 groups was significant (p&lt;0.05). Crude Logistic regression model results revealed that AF was associated with increased risk of MACEs in patients with LVNC [Crude odds ratio (OR) 2.23, 95% confidence interval (CI) 1.19–4.19, p=0.01]. Adjusted Logistic regression model indicated that AF was still an independent risk factor (adjusted OR 2.43, 95% CI 1.08–5.45, p=0.03) for MACEs after adjusting for other risk factors including age, heart rate, syncope, heart failure, NYHA class, cardio-pulmonary resuscitation history, hypertension, prior stroke, prior system embolism, family history of cardiomyopathy, levels of NT-pro-BNP, left atrial diameter, left ventricular ejection fraction, oral anticoagulant therapy and antiplatelet therapy.

Conclusion
This current study indicated that AF is associated with a worse prognosis in patients with LVNC. Extra attention is needed in clinical practice for LVNC patients with AF.

Funding Acknowledgement
Type of funding sources: None.
Do female patients with hypertrophic cardiomyopathy have a worse prognosis than male patients?
Authors: Bonaventura J , Vejtasova V , Polakova E , Rihakova B , Veselka J 
Published: October 2022

Abstract

Aim
Sex affects the prognosis of many cardiovascular diseases. This study aimed to assess the predicted sudden cardiac death (SCD) risk and evaluate the actual survival between male and female patients with hypertrophic cardiomyopathy (HCM).

Methods
We included 573 HCM patients diagnosed between 1998 and 2021 in a tertiary cardiovascular centre. We compared the SCD prediction values, both European (ESC) and American (ACC/AHA) systems, the ICD (implantable cardioverter-defibrillator) implantation rates and the long-term survival analysis.

Results
There were 240 (41.8%) females with HCM. Total number of 62 ICDs (10.8%) were implanted, 39 in males, 23 in females (11.7% vs 9.6%, p=0.49). Average calculated ESC SCD risk was 2.71% in 5 years; 2.77% in males, 2.65% in females (p=0.81). Average number of ACC/AHA major risk SCD factors was 0.25; 0.25 in males and 0.24 in females (p=0.94). Mean length of follow-up (FU) was 9.2 years, median 8.6 years. Total of 100 patients died during FU, 42 (12.6%) males a 58 (17.5%) females (Figure 1). The cause of death is attached in the Figure 2. Mean age at diagnosis was 48.9 years in males, 57.3 years in females, difference 8.4±1.3 years (95% CI 5.8–10.9, p&lt;0.01). Mean left ventricular wall thickness (LVWT) was 18.5 mm in males, 18.0 mm in females, not statistically significant difference (0.5±0.4 mm; 95% CI −1.3–0.3; p=0.22). In Cox-regression model, female sex was not identified as an independent predictor of mortality, on the contrary of age and LVWT (Figure 2).

Conclusion
In our patients, we predicted a low risk of SCD using both ESC and ACC/AHA models. The finding aligns with a relatively low number of implanted ICDs and actual survival rates. Female patients seemed to have a worse prognosis, probably due to older age at diagnosis and non-SCD causes of death.

Funding Acknowledgement
Type of funding sources: None.
Exercise unmasks impaired vascular and cardiac hemodynamic in patients with hypertrophic cardiomyopathy
Authors: Tamargo M , Martinez-Legazpi P , Gutierrez E , Espinosa M A , Mendez I , Fernandez A I , Prieto-Arevalo R , Gonzalez-Mansilla A , Mombiela T , Sanz-Ruiz R , Elizaga J , Yotti R , Fernandez-Aviles F , Bermejo J 
Published: October 2022

Abstract

Background/Introduction
Exertional dyspnea is a common finding in patients with Hypertrophic Cardiomyopathy (HCM), yet little data is available regarding the hemodynamic disturbances that lead to symptom development in this population.

Purpose
To investigate the mechanisms involved in the functional limitation of patients with HCM.

Methods
We prospectively studied 20 symptomatic patients with confirmed diagnosis of HCM. Assessment included NT-pro BNP levels, echocardiogram, and invasive characterization, where subjects also underwent invasive cardiopulmonary exercise testing.

Results
Median patient age was 57 (48–66) years old and 15 (75%) were male. Basal NT-pro BNP was elevated (748 pg/mL [406–1082]) and 8 (40%) subjects had NYHA functional Class III despite optimal medical treatment. Sarcomeric abnormal mutations were identified in 12 subjects (60%), most frequently in MYBPC3. Ultrasound imaging showed marked left ventricle (LV) hypertrophy (LV Mass Index 140 g/m2 [109–161]), with signs of LV outflow obstruction in 13 (65%) subjects. All patients displayed preserved ejection fraction (68% [61–73]). Significant mitral regurgitation was present in 5 subjects and median E/e' was 9.87 [6.43–13.14].
At rest, biventricular filling pressures were relatively normal, with upper limit mean Pulmonary Pressure (Table). Patients exercised for 6.4 (95% CI: 5.6–7.2) min, achieving a respiratory exchange ratio of 1.11 (1.02–1.17). All subjects displayed normal cardiac output at rest (5.6 L/min (3.7–7.5)), that increased during exertion, due mostly to a rise in heart rate (p&lt;0.0001). Exercise doubled LV End-Diastolic Pressure from 15.3 (11.5–19.1) mmHg at baseline to 30.4 (26.6–34.3) mmHg at peak VO2 (p&lt;0.0001), whereas mean pulmonary pressure increased from 21 (14–29) mmHg to 40 (33–47) mmHg (p&lt;0.0001).
Remarkably, although arterial hemodynamics were relatively normal at baseline, exercise induced significant increases both in the continuous (systemic vascular resistance) and pulsatile components of vascular load (Impedances, p&lt;0.05; Table 1) (Figure 1). This increase in afterload during exertion has not been previously documented in HCM. The decreased compliance derived, can also play a role in the elevated filling pressures documented on exertion.

Conclusion
Exercise unmasks adverse hemodynamics in HCM, severely increasing LV filling pressures and showing systemic arterial dysfunction.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Spain.
Genotype-phenotype correlation and allele dating analysis of a novel variant in hypertrophic cardiomyopathy: p.Arg652Lys in MYH7
Authors: Antoniutti G , Caimi-Martinez F , Alvarez-Rubio J , Morlanes-Gracia P , Pons-Llinares J , Rodriguez-Picon B , Fortuny-Frau E , Torres-Juan L , Hernandez-Rodriguez J , Heine-Suner D , Ripoll-Vera T 
Published: October 2022

Abstract

Background/Introduction
Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband's risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers.

Purpose
The objectives of the present study are to assess the genotype-phenotype correlation of a novel variant found in patients with HCM and explore the possibility of a founder effect in the Balearic Islands, Spain.

Methods
We performed an observational study with phenotype description and genotype correlation of patients with HCM in whom we found a novel variant in the MYH7 gene (NM_000257.4:c.1955G&gt;A) which putatively causes a p.Arg652Lys missense protein change.
We did IBD/coalescent-based allele dating analysis of this novel variant.

Results
This previously non-described variant was found in twelve families with HCM. Out of those, 59 patients corresponding to 8 families were clinically characterized with a median follow-up of 63 months. Among them, 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator dis-charge, an embolic event, or admission for heart failure) was observed in five (20%) patients.
This p.Arg652Lys variant was classified as likely pathogenic (LP) and associated with the development of HCM for the following reasons: 1) It is found in patients with HCM, but not in controls, 2) There is evident segregation with HCM on the 8 families described, and 3) It is located in an active site of the protein where a variant in the same amino acid has already been clearly established as pathogenic (p.Arg652Gly).
Interestingly, the exclusive presence of the variant in our region could correspond to a founder effect in the Balearic Islands, Spain, which we have further investigated. IBD/coalescent-based allele dating analysis reveals that the origin of this allele is 96 generations away which would correspond to 1900–2400 years ago, when the Balearic Islands were already populated.

Conclusions
We can define the p.Arg652Lys variant in MYH7 as LP in HCM and a founder effect is in the Balearic Islands is highly probable due to the exclusive presence at the region and the dating analysis of it.

Funding Acknowledgement
Type of funding sources: None.
Metoprolol improves left ventricular longitudinal function at rest and during exercise in obstructive hypertrophic cardiomyopathy
Authors: Dybro A , Rasmussen T B , Nielsen R R , Pedersen A L D , Andersen M J , Jensen M K , Poulsen S H 
Published: October 2022

Abstract

Background
Hypertrophic cardiomyopathy (HCM) patients with outflow obstruction often experience symptoms of heart failure upon exertion. We aimed to characterize left ventricular (LV) systolic function by segmental and global longitudinal strain echocardiography, and to investigate changes in relation to exercise, and the effect of standard treatment with beta-blockers.

Method
Twenty-nine patients with obstructive HCM and New York Heart Association (NYHA) class ≥ II symptoms were enrolled in a double-blind, placebo-controlled, randomized crossover trial. Patients received metoprolol 150 mg or placebo for two consecutive two-week periods in random order. Echocardiographic assessment with speckle-tracking derived longitudinal strain (LS) was performed at rest and during peak exercise at the end of each treatment period. Segmental LS was calculated as the mean of the six apical, mid, and basal segments.

Results
During placebo treatment resting values of segmental LS showed an apical-basal difference of −10.3% (95% confidence interval (CI): −12.7 to −7.8; p&lt;0.0001), with severely depressed values of the basal segment −9.3 (4.2) %. Treatment with metoprolol improved LS of the apical segment (−2.8%; 95% CI: −4.2 to −1.3; p&lt;0.001) and mid segment (−1.1%; 95% CI: −2.0 to −0.3; p=0.007). The segmental improvement with metoprolol treatment was reflected in an increase in resting global LS (LV GLS) (−1.4%; 95% CI: −2.3 to −0.6; p&lt;0.001). Peak exercise was associated with a reduction in LV GLS, yet the improvement in LV GLS during metoprolol was consistent upon exercise (−1.3%; 95% CI: −2.6 to −0.1; p=0.03).

Conclusion
Segmental LS of the LV in obstructive HCM showed an abnormal apical-basal difference. Exercise was associated with a reduction in LV GLS, illustrating an impaired myocardial functional reserve capacity. Metoprolol significantly improved LS of the apical and mid segments of the LV at rest and LV GLS during exercise.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Novo nordic foundation