bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased risk of out-of-hospital cardiac arrest in patients with congenital heart disease: a nationwide study
Authors: Barcella C A , El-Chouli M , Malmborg M W , Folke F , Gislason G
Published: October 2022

Background

The last four decades witnessed substantial improvements in treatment of congenital heart disease (CHD) leading to most children surviving into adulthood. Currently, the number of adults with CHD surpasses that of children. The shift in the CHD population's age composition necessitates focusing on long-term problems. A significant, but not well-investigated, issue is the risk of out-of-hospital cardiac arrest (OHCA) in adults with CHD.

Purpose

To investigate overall and temporal changes in the rate of OHCA associated with CHD compared with the general population.

Method

We conducted a nested case-control study matching all adult patients with OHCA of presumed cardiac cause between 2001 and 2015 with up to five controls from the entire Danish population on age, sex, date of OHCA and cardiac comorbidities status (at least one among ischemic heart disease, heart failure and presence of implantable cardioverter-defibrillator). Patients with CHD were identified using in- and out-patient hospital diagnoses any time prior to OHCA and divided into two mutually exclusive subgroups, either non-severe or severe CHD. The subclassification of CHD is based on a hierarchical approach previously used, where at least one severe CHD diagnosis is required to be classified as severe.

We used Cox regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI) of OHCA. We stratified on CHD status (non-severe, severe or control), sex and OHCA year group (2001–2008 vs 2009–2015).

Results

We included 35,005 OHCA cases and 175,025 controls: the median age was 72 years, 66.9% were male and 34.6% had cardiac comorbidities. In total, among cases, we identified 103 patients with non-severe CHD and 51 with severe CHD, while, among controls, 247 with non-severe CHD and 69 with severe CHD. Both non-severe and severe CHD were overall associated with higher rates of OHCA compared with the general population: HR 2.11 (95% CI, 1.68–2.66) and HR 3.93 (95% CI, 2.71–5.69), respectively (Figure A). We found similar results when we stratified the analyses according to the presence of cardiac comorbidities at date of OHCA (Figure B) and sex.

When stratified by OHCA year group, we observed stable rates of OHCA associated with non-severe CHD: from HR 2.03 (95% CI, 1.36–3.03) in the period 2001–2008 to HR 2.15 (95% CI, 1.62–2.86) in the period 2009–2015. Conversely, we observed a trend towards decreasing rates of OHCA associated with severe CHD: from HR 5.04 (95% CI, 2.79–9.11) in the period 2001–2008 to HR 3.10 (95% CI, 1.80–5.19) in the period 2009–2015

Conclusions

Non-severe and severe CHD were both associated with higher rates of OHCA compared with the general population. While we observed decreasing rates of OHCA over calendar year for severe CHD, they remained stable for non-severe CHD.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital, Hellerup, Denmark
Marantic endocarditis and cancer: diagnosis, treatment and outcomes: a multicentric cohort study
Authors: Deharo F , Arregle F , Tribouilloy C , Cosyns B , Donal E , Di Lena C , Bohbot Y , Selton Suty C , Bourg C , Hubert S , Casalta J P , Philip M , Martel H , Gouriet F , Habib G
Published: October 2022

Background

Marantic endocarditis (ME) associated with cancer is a rare disease with a poor prognosis. Unlike infective endocarditis (IE), whose diagnosis and therapeutic management are based on strong evidence, ME management solely relies on clinical cases, autopsies and literature reviews of descriptive articles.

Purpose

To describe clinical characteristics, management therapies and outcome of patients presenting with ME associated with cancer. To assess the role of multimodal imaging in the diagnosis of this disease.

Methods

In a retrospective multicentric study including four tertiary centers for treatment of endocarditis in France and Belgium, patients with a diagnosis of ME were included. Demographic, imaging (echocardiography, PET-CT, computed tomography) and management data were collected. Long-term mortality was analyzed.

Results

Between November 2011 and August 2021, 47 patients with a diagnosis of ME were included. Mean age was 65±11 years. ME occurred in 43 cases (91%) on native valves. 89% (42 patients) were left-sided ME and the most common cardiac valve involved were aortic (34 cases, 73%) and mitral (26 cases, 55%). Systemic embolism was frequent (40 patients, 85% of cases). One year mortality was 55% (26 patients). 22 patients (46%) had a known cancer before ME and 25 cases (54%) were diagnosed thanks to paraclinical investigations. Most cancers were lung (19 cases, 40%) following by pancreatic cancers (10 cases, 20%). PET CT was performed in 30 patients (64%) and allowed a new diagnosis of cancer in 14 patients (30%). 41 patients (88%) were treated medically with anticoagulation therapy. 6 patients (12%) underwent valve surgery.

Conclusion

To our knowledge, our study included the largest cohort of patients presenting with ME. The prognosis of ME is poor due to its association with advanced malignancy and related to the frequency of thromboembolic events. Diagnosis of ME is challenging and multimodal imaging, especially PET CT seems to be very useful to distinguish IE and ME by revealing cancers.

Funding Acknowledgement

Type of funding sources: None.
Cutibacterium acnes endocarditis: a multicenter case series
Authors: Heinen F J , Arregle F , Van Den Brink F S , Ajmone Marsan N , Bernts L H P , Kamp O , Roescher N , Verkaik N J , Roos-Hesselink J W , Post M C , Habib G , Tanis W
Published: October 2022

Background

Infective endocarditis (IE) due to Cutibacterium acnes (C. acnes) (formerly known as Propionibacterium acnes) is challenging to diagnose. It is suggested that patients often present without fever nor inflammatory parameters. Meanwhile, cardiac abscesses and valve dysfunction are often reported, with a high percentage of patients requiring cardiac surgery [1–7]. No study has yet confirmed the atypical presentation of IE caused by C. acnes.

Purpose

To study clinical characteristics and outcomes of patients with C. acnes IE.

Methods

A multinational retrospective case series was conducted. Patients who were diagnosed with definite IE according to the modified Duke criteria between 2010 and 2020 were included. There were six participating hospitals. Cases were identified by positive blood cultures or positive valve/prosthesis cultures. Clinical data was retrieved from medical records.

Results

We identified 61 cases of C. acnes IE. Patients were predominantly male (n=58, 95%) and had previous cardiac surgery (n=56, 91.8%), which in most cases consisted of aortic valve replacement or Bentall procedures (n=34, 60.7% and n=13, 23.2% respectively). The median time between index surgery and presentation was 31 months (IQR 15.9–69.3). At presentation, fever was absent in 59% of patients (n=36). Most patients experienced symptoms for one to two weeks prior to hospital presentation (41%). At presentation, the median CRP level was 35.5 mg/L (IQR 10.0–70.8). Moreover, in 23% of patients (n=14), the median CRP level was not elevated (<10.0 mg/L). The median leucocyte count at presentation was 9.8x109/L (IQR 8.0–12.3), and thus not exceeding the upper limit of the normal range (10.0x109/L). Approximately half of the blood cultures became positive. In addition, the median time to positivity of blood cultures was seven days (IQR 6–9) and 82.4% of patients had a time to positivity of more than five days. (Redo) surgery was performed in 40 patients (65.5%). Peroperatively, valve dehiscence was observed in 19 patients (47.5%) and vegetations and abscesses were present in 16 patients (40%). The 30-day and one-year mortality rates were 4.9% and 11.5% respectively. Eight patients experienced relapse IE during follow-up of which seven initially received conservative treatment.

Conclusion

IE due to C. acnes predominantly concerns males with prosthetic heart valves. The diagnostic process in C. acnes IE is difficult due to its atypical presentation, with frequent absence of fever and inflammatory parameters. Meanwhile, blood cultures remain negative in approximately half of the patients. Moreover, the time to positivity of blood cultures is one week, which further delays the diagnostic process. Redo surgery is required in a high percentage of patients.

Funding Acknowledgement

Type of funding sources: None.
The predictive value of left atrial diameter for thrombotic risk in patients with left ventricular noncompaction
Authors: Xu W
Published: October 2022

Purpose

Patients with left ventricular noncompaction (LVNC) are associated with increased risk of thromboembolism including system embolism (SE) and stroke. Moreover, left atrial (LA) diameter was proved to be a strong predictor for stroke and SE [1]. This study aimed to evaluate the predictive value of left atrial diameter on the risk of thromboembolism in patients with LVNC.

Methods

This retrospective longitudinal study enrolled 302 patients (median age 46 years, 65.9% male) diagnosed as LVNC through echocardiography or cardiac nuclear magnetic according to Jenni criteria [2] and Petersen criteria [3], respectively. The primary endpoint was thromboembolism events including SE and stroke.

Results

The 302 patients with LVNC were divided into 2 groups: large LA group (LA diameter ≥43mm, n=155) and small LA group (LA diameter<43mm, n=147), according to the median of LA diameter. After a median follow-up of 4.3 years, 19 cases (6.3%) patients occurred thromboembolism events. In the large LA group, 16 patients (10.3%) occurred thromboembolism events while there were 3 cases (2.0%) suffering from SE/stroke in the small LA group (p<0.05). The Kaplan-Meier curves (Figure 1) compared by the log-rank test showed that the large LA group was associated with a higher risk of thromboembolism events and the difference between the 2 groups was significant (p<0.05). Crude Cox regression model results revealed that LA diameter was an independent risk factor for thromboembolism events in patients with LVNC (Crude HR 1.07, 95% CI 1.02–1.12, p=0.004). After adjusting for prior heart failure, NYHA class, atrial fibrillation, prior stroke, coronary artery disease, pulmonary arterial hypertension, family history of cardiomyopathy, LA diameter was still associated with increased thrombotic risk (Adjusted HR 4.98, 95% CI 1.07–23.04, p=0.04). Moreover, the ROC curves (Figure 2) showed that the AUC of LA diameter was 0.692 and even better than the CHA2DS2-VASc score (AUC=0.576).

Conclusion

The current study indicated that LA diameter is an effective predictor of thrombotic risk in patients with LVNC. Moreover, extra attention is needed in LVNC patients with larger LA diameters for the risk of thromboembolism.

Funding Acknowledgement

Type of funding sources: None.
Evaluating risk factors, biomarkers and management of myocarditis following treatment with checkpoint inhibitors. A retrospective analysis
Authors: Abdimalik M , Dawoodji A , Olsson-Brown A , Dobson R
Published: October 2022

Immunotherapy is an exciting treatment of many malignancies. They upregulate the immune system to attack cancerous cells. Immune checkpoint inhibitor (ICIs) are among armamentarium of immunotherapy agents that target immune system negative regulation and are known to induce myocarditis [1]. This is a rare but increasingly recognised complication as immunotherapy regimens become more widely used as first line therapy for a range of tumour types. Due to its infrequent presentation, there remains uncertainty regarding its diagnosis and management [2]. We conducted a single centre retrospective analysis of patients undergoing immunotherapy at a cancer centre in United Kingdom. The cases were referred to the regional cardio-oncology service for suspected myocarditis.

In this single center retrospective analysis, data of 60 patients with suspected myocarditis (based on symptoms, cardiac biomarkers or ECG) presenting over a 2 year period were evaluated. Of those 25 (42%) developed MRI-proven myocarditis with mean period to toxicity post treatment of 99.5 days. In the same time period 1027 patients experienced all-type immunotherapy related adverse events (irAEs) thus myocarditis accounted for 2.4% of all ICI-induced toxicity. 35% had significant pre-existing cardiac history including ischaemic heart disease, valvular disease and ventricular impairment. Patients with myocarditis had average peak troponin of 276 and average peak pro-BNP of 2,265. Less than 10% of patients with myocarditis had pre-existing autoimmune diagnosis (rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease). Average maximum grade toxicity was 3.

The majority of patients were managed with steroids with 48% receiving intravenous methylprednisolone followed by oral prednisolone and 28% patients receiving only oral steroids. 44% of patients also required steroid sparing agents such as tacrolimus or mycophenalate mofetil. Steroid tapering was adjusted based on the patient's symptoms with 32% of patients needing dose escalation for a flare. No patients restarted immunotherapy once myocarditis had been identified and overall survival remained comparable to those without myocarditis.

In conclusion, myocarditis is a late complication of ICIs with higher incidence among patients with significant cardiac history. Associated biomarkers are significantly elevated and correlate well with the presence of myocarditis. Steroids remain the mainstay of treatment for those who develop myocarditis secondary to immunotherapy but there is also an important role for other agents such as tacrolimus or mycophenalate mofetil.

Funding Acknowledgement

Type of funding sources: None.
Immediately improved LA function demonstrated with pulmonic vein Doppler-intraoperative TEE in TAVR patients
Authors: Wuttichaipradit C , Reinthong R , Wongsinkongman C , Tunhasiriwet A , Muangsilprasart V , Preeyanont P , Jeamanukoolkij A , Aramsereewong T
Published: October 2022

Background

Recent studies exhibited the immediately improved left atrium (LA) function by Doppler mitral inflow and mitral annular velocity by tissue Doppler and left atrial appendage flow velocity. This study aims to investigate the improvement of LA function by pulmonic vein Doppler parameters performing by an intraoperative transesophageal echocardiogram (TEE) during transcatheter aortic valve replacement (TAVR).

Material and methods

Patients who underwent TAVR from January 2020 to September 2021 and pulmonic vein Doppler were acquired by TEE (right upper pulmonic vein from 90–110° mid-esophageal view) during TAVR with the explicit image. We obtained S-, D-, A-wave velocity; LV end-diastolic pressure (LVEDP) and mean pressure gradient across aortic valve (mean-AVPG) from invasive catheter both pre-TAVR and immediate post-TAVR. All parameters between pre-TAVR and post-TAVR were compared with paired t-test.

Results

38 patients (mean age 79.7±5.6 years, 17 female) were enrolled in this study. S-wave was only significant parameter with increased velocity from baseline (30.3±24.6 cm/s vs 50.2±23.2 cm/s, p<0.001), whereas D-wave and A-wave were not significantly changed from baseline (35.1±15.2 cm/s vs 33.7±11.0 cm/s, p=0.6; and 14.3±8.6 cm/s vs 13.0±8.9 cm/s, p=0.4, respectively). LVEDP was not significantly changed from baseline (19.6±9.5 mmHg vs 18.7±8.1 mmHg, p=0.49) but mean-AVPG was significantly decreased after TAVR (53.8±11.8 mmHg vs 6.1±5.6 mmHg, p<0.001). We also noted 25 patients who had S/D ratio <1 at baseline, 19 of 25 patients were changed to S/D ratio >1 immediately post TAVR.

Conclusion

This study demonstrated the improved LA function with pulmonic vein Doppler after TAVR.

S-wave is the only parameter to be improvement immediately post TAVR and change to S/D ratio >1 in majority of patients.

Funding Acknowledgement

Type of funding sources: None.
Genetic testing in consecutive cases of acute and clinically suspected myocarditis with noise in the family
Authors: Papatheodorou E , Pantou M , Gourzi P , Bakalakos A , Tsatsopoulou A , Vlagkouli V , Rammos S , Papagiannis J , Efraimidis M , Degiannis D , Vardas P , Anastasakis A
Published: October 2022

Background

Myocarditis is increasingly associated with dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM).

Purpose

The aim of our study was to define if a genetic predisposition exists in cases of myocarditis with suspicious findings of inherited cardiovascular disease (noise) in the family.

Methods

Consecutive patients referred to our unit from 2010 to 2021, with a presentation of acute or clinically suspected myocarditis, as defined by current criteria, went through family screening of the first and second-degree relatives. Patients fulfilling typical criteria for definite ARVC upon presentation were excluded. Patients with suspicious familial findings (familial noise) including a. family history of sudden cardiac death, b. family history of myocarditis or cardiomyopathy or c. findings suggestive of cardiac disease in the relatives (ECG abnormalities, complex or frequent ventricular arrhythmias, conduction disease, troponemia, structural abnormalities suggestive of cardiomyopathy) went through genetic analysis for 90 genes associated with cardiomyopathy.

Results

Fifty-five patients with myocarditis and familial noise were included (Table 1). In 49 (89%) patients ≥2 diagnostic criteria for clinically suspected myocarditis were fulfilled. In 50% of the patients, the noise in the family was revealed upon familial screening as there was no relevant family history. Myocardial inflammation was confirmed in 16 (29%) patients with histological findings on endomyocardial biopsy or ≥2 Lake Louise Criteria on cardiac magnetic resonance. Pathogenic or likely pathogenic variants were identified in 78% of the cases (figure 1). Desmoplakin (24%) followed by lamin A/C (13%) and titin (9%) were the most common genes identified. In cases with confirmed myocardial inflammation the genetic yield increased to 87%.

Conclusions

A significant proportion of myocarditis patients with “familial noise” carry a pathogenic genetic variant in a cardiomyopathy related gene. These findings potentially affect the clinical management and need for family and genetic screening in patients with clinically suspected myocarditis.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Greek Network for Precision Medicine in Cardiology and the Prevention of Sudden Cardiac Death in the Young, icardiacnet
Prognostic implication of neutrophil-lymphocyte ratio (NLR) in myocarditis: results from a multicentre, multinational study
Authors: Sadler M , Cannata A , Baggio C H I A R A , Monzo L , Scott P , Piper S , Sinagra G , McDonagh T , Merlo M , Bromage D
Published: October 2022

Background

Neutrophil–lymphocyte ratio (NLR) is an accessible inflammatory biomarker. Recently, baseline NLR has been shown to be independently associated with incident cardiovascular (CV) events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated. The aim of the present study was to investigate the prognostic value of NLR in patients with AM.

Methods

All consecutive patients with a diagnosis of AM admitted to three tertiary referral cardiac centres in two countries between October 2006 and June 2020 were included in the study. Diagnosis was confirmed by either cardiac magnetic resonance or endomyocardial biopsy. The outcome measure was all-cause mortality. Patients were divided into two groups according to NLR value defined in previous studies (i.e., 2.5).

Results

A total of 287 patients with AM were included in the study. Baseline characteristics were comparable in both groups. Approximately two thirds of patients were males (n=194, 68%) with a mean age of 39±16 years. The main clinical presentation was predominantly infarct-like (n=215, 75%), followed by heart failure (HF) (n=46, 16%) and arrhythmic (n=26, 9%). Patients admitted with a HF presentation were more prevalent in the group with elevated NLR, while no difference was found in the other clinical presentations. For all patients, ECG features were comparable between groups. However, patients with elevated NLR presented with slightly higher LVEF (55±11% vs 50±13% respectively, p=0.003). Over a median follow-up of 54 months, higher NLR was associated with worse prognosis (Figure 1, p=0.02). Patients with high NLR have a 7-fold higher risk of adverse events during follow-up (Hazard Ratio 7.83, 95% confidence interval 1.02–59.89, p=0.047).

Conclusions

NLR is a promising and accessible inflammatory biomarker. In patients with AM, elevated NLR is associated with worse prognosis. Further research is advocated to confirm these data in larger populations.

Funding Acknowledgement

Type of funding sources: None.
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

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 (<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<0.05) and 8.4±9.6% (p<0.05), and a reduction of LVEDD by 3.8±6.1mm (p<0.05) and 1.0±7.7mm (p>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

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

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

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<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<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

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<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

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<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<0.0001), whereas mean pulmonary pressure increased from 21 (14–29) mmHg to 40 (33–47) mmHg (p<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<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

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>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

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<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<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<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
Clinical, functional and prognostic correlates of excess left ventricular force in hypertrophic cardiomyopathy
Authors: Palinkas E D , Marchi A , Milazzo A , Tassetti L , Zampieri M , D'Alfonso M G , Mori F , Palinkas A , Ciampi Q , Sepp R , Olivotto I , Picano E
Published: October 2022

Background

Excess force generation during myocardial contraction represents a cardinal feature of hypertrophic cardiomyopathy (HCM).

Purpose

To evaluate the anatomical, functional and prognostic correlates of left ventricular (LV) force in HCM.

Methods

We prospectively recruited a consecutive sample of 408 HCM patients with LV ejection fraction (EF) >50%, referred for baseline transthoracic echocardiography in 2 primary HCM centers in Hungary and Italy between 1999 and 2021. LV force was calculated as LV outflow tract gradient+systolic blood pressure/LV end-systolic volume. Patients were followed for a median of 107 months (IQ range, 58–158 months), the study endpoint was all-cause mortality.

Results

Mean LV force was 6.0±4.6 mm Hg/ml. Receiver-operating characteristic analysis identified 7.5 mm Hg/ml the best cut-off value to predict mortality. LV force >7.5 mm Hg/ml was present in 86 patients (21%), more frequently in women (58 vs 27%, p<0.0001), more often in patients with diabetes (16 vs 6%, p=0.003), beta-blocker (81 vs 58%, p<0.0001), calcium channel-blocker (19 vs 9%, p=0.012) and diuretic therapy (19 vs 8%, p=0.004), compared to patients with LV force ≤7.5 mm Hg/ml. Patients with excess LV force had more advanced NYHA class (1.8±0.7 vs 1.4±0.7, p=0.0001), greater left atrial diameter [(LAd), 46.7±6.6 vs 43.0±7.2 mm, <0.0001], LV maximal wall thickness (23.2±5.5 vs 21.6±5.5 mm p=0.01), LV EF (74.6±6.4 vs 67.0±6.8%, <0.0001), mitral regurgitation grade (1.2±0.7 vs 0.7±0.7, p<0.0001) and E/e' (10.3±5.0 vs 7.8±5.0, p=0.005). During follow-up 43 deaths occurred. All-cause death was more frequent in patients with excess LV force (21 vs 8%, p<0.0001). At multivariable Cox regression analysis, excess LV force was an independent predictor of mortality (HR 2.9, 95% CI 1.14–7.26, p=0.025) independent of age (HR 1.03, 95% CI 1.00–1.05, p=0.022) and LAd (HR 1.07, 95% CI 1.02–1.14, p=0.005).

Conclusion

LV force with a threshold of 7.5 mm Hg/ml, independently predicts adverse outcome in patients with HCM and preserved systolic function. Excess LV force generation is associated with female sex, diabetes, NYHA class, medications, LAd, LV wall thickness, EF, mitral regurgitation grade and E/e'.

Funding Acknowledgement

Type of funding sources: None.