bluuebunny/crossref_metadata_2025 huggingface dataset:
Endomyocardial biopsy practice in non-transplant patients: a nationwide descriptive study
Authors: Guiraud-Chaumeil P , Segol E , Leclerc Du Sablon N , Baudet M , Biassette H , Logeart D
Published: November 2023

Background

Endomyocardial biopsy (EMB) is an invasive diagnostic tool, mainly used during the follow-up of heart transplant patients (HTx). Its others indications have been established and discussed in position statement paper from international cardiac societies. However the use of EMB in real life remains controversial and differs widely from a center to another.

Purpose

We carried out a nationwide survey to describe the current use of EMB in non-heart transplant patients.

Methods

We used the National Hospital Discharge Database (PMSI) that contains diagnostic codes of all hospitalizations. Medical data is coded from different sources (e.g. laboratory reports, discharge reports) according defined terminologies and coding rules. We included all hospitalizations during which EMB (code CCAM DAHF001 – Endocardium or Myocardium Biopsy, transcutaneous vascular access) was performed from January 1st 2019 to December 31th 2020. We excluded all patients with a main or secondary or associated diagnosis of heart transplant. Main diagnosis as well as secondary and associated diagnoses were collected in order to define the medical indication of EMB. We aggregated EMB indications into 8 groups.

Results

Among 9735 EMB, 914 (9%) were carried out for non-transplant patients during the 2 years of analysis. Among the 212 hospitals with interventional cardiology units, only 53 (25%) carried out EMB in non-transplant patients and 86% of these procedures were carried out in transplant centers. Three hospitals carried out 37% of all non-transplant EMB while 23 centers carried out no more than 5 EMB over the 2-year survey.

The figure displays main indications of EMB in non-transplant patients. According to the PMSI database, the 3 main indications of EMB were amyloïdosis (29%), non-ischemic Dilated Cardiomyopathy (28%) and myocarditis (22%). The medical indication could not be specified in 155 (16%) patients.

Conclusion

In non-transplant patients, EMB is rarely performed in France, only in a few hospitals and with significant disparity in the annual rate of procedures carried out by each. Most EMB were performed because of amyloidosis or dilated cardiomyopathy and myocarditis. Further data about local constraints as well as clinical impact of EMB for each patient would be useful to understand further the role of EMB in real life.EMB indications in non HTx patients
The electrophysiological substrate of biopsy-proven cardiac amyloidosis
Authors: Casella M , Compagnucci P , Ciliberti G , Barbarossa A , Valeri Y , Cipolletta L , Volpato G , Stronati G , Vagnarelli F , Lofiego C , Perna G P , Natale A , Basso C , Guerra F , Dello Russo A
Published: November 2023

Background

Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases.

Purpose

The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes.

Methods

We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events.

Results

A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p<0.001); the unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%).

At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]).

Conclusions

In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis
The diagnosis of acute myocarditis in emergency (DAME) score: improving diagnostics within the emergency department
Authors: Ciccone M M , Capriati G , Gambacorta S , Antonica C , Scicchitano P
Published: November 2023

Purpose

The final diagnosis of myocarditis is challenging. The aim of our study was to provide the D.A.M.E. (Diagnosis of Acute Myocarditis in Emergency) Score for the fast identification of patients suffering from myocarditis at Emergency Department (ED).

Methods

This was a multicenter, retrospective study involving three centers. All medical records from January 2010 to December 2014 reporting a final discharge diagnosis of myocarditis were considered. One hundred-four patients (mean age: 40.2±16.5 years) were enrolled. Clinical, biochemical and instrumental data were gathered. Data were analysed by means of logistic regression model and factorial analysis. A validation cohort from a fourth center was enrolled.

Results

The final determinants of the DAME score were six: fever, chest pain, erythrocyte sedimentation rate (ESR) > 20 mm/h, C-reactive protein (hs-CRP) >3 mg/L, troponin serum levels >3 ng/L, and left ventricle ejection fraction < 50%. All of them received a specified score ranging from 0 to 4. A score > 4 was related to 75% probability of myocarditis; a final score ranging between 1 and 4 was related to 57% probability of myocarditis. ROC curve on the validation cohort (289 patients, 27 with myocarditis) demonstrated the best cut-off to be 7: AUC 0.958 (p< 0.001), sensibility: 100%, specificity: 85.11%, PPV: 40.9%, NPV: 100% (LR+: 6.72; LR-: 0.00). Logistic regression analysis revealed Odds Ratio equal to 2.83 (95% CI 1.90 - 4.20, p < 0.0001).

Conclusions

DAME score can offer a reliable tool in ED setting for the evaluation of patients suffering from suspected myocarditis.
Imaging for prevalence assessment of cardiac transthyretin amyloidosis in patients > 60 years hospitalized in cardiology : the IMPACT study
Authors: Beard E , Alos B , Khalifa B , Rosenberg T , Lequeux B , Ragot S , Saulnier P J , Boucher C , Christiaens L P , Bouleti C
Published: November 2023

Introduction

Transthyretin cardiac amyloidosis (ATTR-CA) is a severe condition with poor prognosis if left untreated (1). Its true prevalence remains unknown because of frequent underdiagnosis, and most published series have focused on highly selected populations (2-3). The objectives of this prospective study were 1) to determine the prevalence of ATTR-CA in consecutive patients > 60 years hospitalized in cardiology wards and presenting with left ventricular hypertrophy (LVH) ≥ 12 mm on transthoracic echocardiography (TTE), using a systematic 99mTc-HMDP bone scintigraphy for diagnosis screening 2) to analyze the characteristics associated with the final diagnosis of ATTR-CA. Population & methods: Between october 2021 and june 2022, 251 patients with echocardiographic LVH (from any cause, including high blood pressure or aortic stenosis) and without any previous diagnosis of CA, were prospectively included and underwent 99mTc-HMDP bone scintigraphy. A monoclonal gammapathy was systematically sought-after to exclude light-chain cardiac amyloidosis (AL-CA) (4). Genetic analysis of the TTR gene was systematically performed in case of definite diagnosis of ATTR-CA. The design of the trial is provided in Figure 1. This is an interim analysis of a private funded study currently being finalized, with a target of 400 patients to be included.

Results

Among the 251 patients, definite ATTR-CA was diagnosed in 17 patients (6.8%), all of them being wild-type. No AL-CA was identified. The 2 subgroups of patients with the highest prevalence of ATTR-CA (>10%) were patients ≥ 65 years with either heart failure or bilateral carpal tunnel syndrom. The majority of diagnosed patients had symptoms or signs suggestive of ATTR-CA, even though CA was never looked-after during their medical pathway, while 30% had no or only one red flag of ATTR-CA. Using multivariable analysis, we found four parameters independently associated with the diagnosis of ATTR-CA as presented in Table 1, one clinical and three echocardiographic, including the alteration of left atrial strain.

Conclusion

We report a high prevalence (6.8%) of ATTRwt-CA in a non-selected cardiological population with LVH from any cause. Most patients were underdiagnosed since they had at least 2 red-flags for ATTR-CA, thus emphasizing the need for continuous and strengthened education on CA. On the other hand, 30% of patients had no obvious sign for CA and the diagnosis was only established by our systematic screening strategy. We report 4 factors significantly associated with ATTR-CA in our population, including the alteration of left atrial reservoir strain. These new data confirm the interest of a complete echocardiographic analysis in case of LVH, to refine the selection of patients who could benefit from 99mTc-HMDP bone scan screening.Study designPredictive factors of ATTR-CA
Immunomodulation to target biopsy-proven myocardial inflammation in genetic cardiomyopathies: a pilot report
Authors: Peretto G , De Luca G , Di Resta C , Campochiaro C , Villatore A , Palmisano A , Vignale D , Busnardo E , Lazzeroni D , Rizzo S , Sala S , Esposito A , Basso C , Dagna L , Della Bella P
Published: November 2023

Background

Preclinical data support the rationale for targeting myocardial inflammation (M-Infl) in genetic nonischemic cardiomyopathies. However, no consistent clinical reports have been provided so far.

Purpose

To provide a pilot report on multimodal detection and targeting of biopsy-proven M-Infl in genetic cardiomyopathies.

Methods

We describe a series of patients (n=25) with genetic cardiomyopathy and M-Infl proven by endomyocardial biopsy (EMB). Multimodal diagnostic workup was extensively applied. Patient-tailored immunomodulatory therapy (IMT) was empirically started to target M-Infl whenever feasible. Multiple outcomes were retrospectively assessed by a dedicated multidisciplinary disease unit.

Results

Patients carrying desmosomal (DGV), cytoskeletal (CGV) and other gene variants, were 12 (48%), 10 (40%), and 3 (12%), respectively. DGV carriers uniformly presented with myocarditis-like chest pain and ventricular arrhythmias, whereas heart failure symptoms were found only in CGV carriers. Dilated cardiomyopathy phenotype and ring-like pattern on cardiac magnetic resonance allowed the best discrimination among genotypes. Noninvasive imaging was concordant with EMB in detecting M-Infl in 21 patients (83%). IMT was started in 17 patients (71%) with no safety issues. By the end of follow-up (median 69 months, range 21-182), signs of M-Infl were documented in 6/18 IMT receivers (33%) and 4/7 untreated cases (57%). For most genotypes, paucity of adverse events was noted while on IMT as compared to the off-treatment period.

Conclusion

Our preliminary data provide a clinical rationale for the research and targeting of M-Infl in a spectrum of genetic nonischemic cardiomyopathies.
Efficacy of cardiac myosin inhibitors for obstructive hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomised controlled trials
Authors: Felix N , Teixeira L M F , Nogueira A K S , Godoi A C , Alexandre F K B
Published: November 2023

Background

Obstructive hypertrophic cardiomyopathy (oHCM) is a hereditary heart disease associated with left ventricular hypertrophy and left ventricular outflow tract (LVOT) obstruction. Cardiac myosin inhibitors (CMI) have emerged as the first disease-specific, non-invasive therapy with promising results in patients with hypertrophic cardiomyopathy. However, its efficacy in the setting of oHCM remains unclear.

Purpose

We aimed to perform a meta-analysis of randomised controlled trials (RCTs) comparing CMI with placebo as a treatment for oHCM in terms of NYHA class improvement, provoked LVOT gradient, and quality of life.

Methods

We systematically searched PubMed, EMBASE, and the Cochrane Library in February 2023 using PRISMA guidelines for RCTs comparing CMI with placebo in oHCM patients. Statistical analyses were performed using R Software version 4.1.0. Between-study heterogeneity was assessed using I2 statistics.

Results

Three RCTs comprising 390 patients were included, of whom 193 (49.48%) were randomised to CMI. CMI were found to be significantly more effective compared with placebo in improving NYHA class (RR 2.23; 95% CI 1.75–2.85; p < 0.001; I2=0%; Fig 1A) and quality of life (SMD 0.64; 95% CI 0.43 to 0.86; p < 0.001; I2=0%; Fig 1B), as well as in reducing provoked LVOT gradients (MD -37.23 mmHg; 95% CI -41.73 to -32.73; p < 0.001; I2=18% Fig 1C).

Conclusion

To our knowledge, this is the first meta-analysis studying CMI versus placebo for the management of oHCM, pointing that CMI were superior to placebo with regards to improvements in NYHA class, quality of life, and LVOT gradients.Figure 1
Myocarditis relapse and COVID19 infection or vaccination: a single-center experience
Authors: Baritussio A , Giordani A S , Basso C , Lorenzoni G , Iliceto S , Marcolongo R , Gregori D , Caforio A L P
Published: November 2023

Background

Myocarditis has rarely been associated with COVID19 infection and it emerged as a possible rare side effect after vaccination with messenger RNA (mRNA) vaccines. Myocarditis may have an unfavorable outcome and may relapse, particularly in females with immune-mediated/autoimmune features and a predisposing immunogenetic background.

Purpose

We aimed to assess the prevalence of myocarditis relapse during CoVid19 outbreak and following the onset of the vaccination campaign in a cohort of patients with history of clinically suspected or biopsy proven myocarditis.

Methods

We included consecutive, randomly selected patients with history of clinically suspected or biopsy proven myocarditis (defined in keeping with the World Health Organization and the European Society of Cardiology (ESC) criteria) coming for a regular follow-up visit to the Cardioimmunology outpatient clinic of a tertiary referral center from September-1-2021 to January-31-2022. History of CoVid19 infection and vaccination status were investigated, and patients underwent clinical, laboratory and echocardiographic check-up (Table1), as per usual practice during planned outpatient follow-up visits. As patients were selected based on already planned follow-up outpatient schedule, to rule out selection bias between the study cohort (n=240) and the remaining patients from our outpatient registry (n=714) we compared clinical, laboratory and imaging features (at baseline and at follow-up) of the two groups.

Results

Out of 240 patients (25% of the 954-outpatient registry cohort) receiving a scheduled follow-up visit, 43 (18%) developed CoVid19 infection, all before vaccination, with mild symptoms; no patient required hospitalization, none developed myocarditis relapse (based upon symptoms, troponin, new ECG or morpho-functional abnormalities at cardiac imaging) during or following CoVid19 infection. Of the 240 patients, 180 (75%) received vaccination, all but 33 with mRNA vaccines; none developed myocarditis relapse, neither early (within 3 weeks from first or second dose) nor later. No differences were found when comparing clinical and diagnostic features between the last follow-up prior to CoVid19 outbreak and the last follow-up by far. There was also no difference in terms of clinical-diagnostic features at baseline and at follow-up between the study cohort (n=240) and the remaining outpatient registry (n=714).

Conclusions

In our randomly selected cohort of patients with history of clinically suspected or biopsy proven myocarditis, both CoVid19 infection and vaccination were uneventful. These data do not support a clinically relevant role of COVID19 infection or mRNA vaccination in triggering myocarditis relapses in patients with prior known myocarditis and reinforce the indication to vaccination also in this patients’ subset, in keeping with a recent ESC consensus document.
Association of epicardial adipose tissue on magnetic resonance imaging with cardiovascular outcomes: Quality over quantity?
Authors: Duca F , Mascherbauer K , Dona C , Koschutnik M , Binder C , Nitsche C , Halavina K , Beitzke D , Loewe C , Bartko P E , Waldmann E , Macherbauer J , Hengstenberg C , Kammerlander A A
Published: November 2023

Background

Quantity of epicardial adipose tissue (EAT) has been associated with poor cardiovascular outcomes. As suggested by computed tomography (CT) studies the quality of EAT may be of incremental prognostic value.

Cardiac magnetic resonance (CMR) is the gold-standard for tissue characterization, however, has never been applied for EAT quality assessment.

Objectives

To investigate EAT quality measured on CMR T1 mapping as predictor of outcome in an all-comer cohort.

Methods

We measured EAT area (EATA) and T1 time (EAT-T1) in a four-chamber views (Figure 1) and tested for association with clinical, demographic, and laboratory parameters using linear regression models. We used Cox-regression analyses to test the association between EATA and EAT-T1 with a composite endpoint of non-fatal myocardial infarction, heart failure hospitalization, and all-cause death.

Results

A total of 966 participants were included (47.2% female, mean age: 58.4years). Mean EATA was 7.3cm2 and mean EAT-T1 was 268ms. On linear regression EAT-T1 was not associated with markers obesity, dyslipidemia or co-morbidities such as diabetes (p>0.05 for all).

During a follow-up of 57.7 months, a total of 280 (29.0%) events occurred. EAT-T1 was independently associated (adj. HR: 1.003, 95%-CI: 1.000 – 1.005, p=0.029, Figure 2) with the composite endpoint when adjusted for established clinical risk factors including age, sex, natriuretic peptide levels, left and right ventricular function, arterial hypertension, body mass index, and coronary artery disease.

Conclusion

In an all-comer CMR cohort, EAT quality, as measured on CMR T1-times, but not EAT quantity is independently associated with a composite endpoint of non-fatal myocardial infarction, heart failure hospitalization, and all-cause death.Figure 1.Regions of interestFigure 2.Kaplan Meier Curves
Sex differences in patients with acute myocarditis: a cohort study
Authors: Buechel J , Balestra G , Haaf P , Marsch S , Kuehne M , Sticherling C , Krisai P
Published: November 2023

Background

Sex differences in patients with acute myocarditis (AM) are poorly understood.

Purpose

We aimed to study sex differences in AM patients including medical history, clinical presentations, diagnostics, and in-hospital outcomes.

Methods

We enrolled 215 patients with a diagnosis of AM at a tertiary hospital between January 2000 and December 2018 into a retrospective cohort study. All patients were hospitalized on an intensive care unit (ICU) with continuous monitoring. We compared sex differences in clinical presentation including ECG, prior medical history, cardiac biomarkers, cardiac imaging (echocardiography and cardiac MRI) and in-hospital outcomes including incident arrhythmia.

Results

Median age was 38 years and 27% were female. Overall, the most common presenting symptoms were chest pain (84%), dyspnea (34%) and fever (29%). Compared to men, women presented more often with dyspnea (47% vs 29%, p=0.015), were older (49 vs 36 years, p<0.001) and had more comorbidities including hypertension (33% vs 18%, p=0.032) and diabetes (14% vs 4%, p= 0.033). In the presenting ECG, female patients were more likely to present with T-wave inversion (46% vs 27%, p=0.017) and less likely with ST elevation (9% vs 39%, p<0.001) compared to male patients. The overall hospital stay was longer in women compared to men (7 vs 5 days, p=0.021) with no difference in the length of ICU stay (2.8 vs 3.0 days, p=0.782). Cardiac biomarkers including high-sensitivity troponin T (median 426 vs 665 ng/l, p=0.415) and CK-MB (median 23 vs 24 U/l, p=0.888) were not different, but women had higher NT-proBNP levels (median 2380 vs 353 ng/l, p=0.032). Left ventricular ejection fraction (LVEF) was similar between sexes, both by transthoracic echocardiography (55% vs 55%, p=0.864) and cardiac MRI (58% vs 56%, p=0.919). During monitoring, atrial fibrillation/atrial flutter occurred in 4% of patients, non-sustained ventricular tachycardia in 15%, sustained ventricular tachycardia in 4% and ventricular fibrillation/cardiac arrest in 2%. While we did not find a sex difference in atrial fibrillation/atrial flutter, women tended to have more severe ventricular arrhythmia (Figure).

Conclusion

Women constituted a quarter of our AM cohort. Compared to men, women were older at the time of AM diagnosis, had more comorbidities, showed different clinical and ECG findings, and were hospitalized longer. While LVEF was similar, women had higher levels of NT-proBNP.Central Illustration
Risk of myocarditis requiring hospitalization following Covid-19 mRNA booster vaccinations
Authors: Arbel R , Yechezkel M , Shmueli E , Yamin D
Published: November 2023

Background

Reports have suggested an association between the development of myocarditis and the receipt of the primary series of messenger RNA (mRNA) Covid-19 vaccines. This association seems to decrease in the first monovalent booster. However, whether this association exists between the second monovalent and first bivalent boosters is unknown.

Purpose

To evaluate the association of the BNT162b2 mRNA booster vaccines and myocarditis events requiring hospitalization.

Methods

We analyzed the medical records of all CHS members aged 12 and above of Clalit Healthcare Services who received the first, second monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and November 15, 2022. We evaluated the risk differences per 10,000 subjects of myocarditis between 28 days before vaccination (baseline period: 35 days until 8 days before vaccination) and after vaccination (post-vaccination: the day of inoculation until day 27) in a pairwise method using the non-parametric percentile bootstrap. The results were stratified by sex and age.

Results

Among 1,965,200 subjects vaccinated with the first booster, 13 events were recorded post-vaccination versus 2 pre-vaccination (risk difference: 0.46; 95% CI: 0.06-0.10). Among 420,888 subjects vaccinated with the second booster, 4 events were recorded post-vaccination versus 1 pre-vaccination (risk difference: 0.07; 95% CI: -0.02-0.19). Among 131,312 subjects vaccinated with the bivalent booster, 0 events were recorded post-vaccination versus 1 pre-vaccination (risk difference -0.08; 95% CI: -0.23-0.00). Table 1 details the results by sex and age group.

Conclusions

The first BNT162b2 booster vaccine was associated with an increased but rare risk for hospitalization events for myocarditis. This association was not observed in the second and bivalent boosters.
Genetic testing in inflammatory cardiomyopathy/myocarditis: a red flag for cardiomyopathy-like histologic findings
Authors: Bueno Marinas M , De Gaspari M , Baritussio A , Cason M , Celeghin R , Pinci S , Giordani A , Carturan E , Rizzo S , Tarantini G , Marcolongo R , Iliceto S , Basso C , Caforio A L , Pilichou K
Published: November 2023

Background

Myocarditis/inflammatory cardiomyopathy is characterized by the presence of an inflammatory infiltrate in the myocardium. Its etiology is heterogeneous, predominantly mediated by viral infection, as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Outcome could vary from a complete recovery to a residual myocardial injury with the subsequent development of dilated cardiomyopathy (DCM). The factors that play a role in the disease progression are not clear, but it has been shown that inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis.

Purpose

To characterize the genetic background of inflammatory cardiomyopathy affected patients to determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in cardiomyopathy-related genes and correlate to histopathologic findings in endomyocardial biopsies (EMB).

Methods

Eighty-nine myocarditis-affected patients (mean age 43±14, 55 males) underwent genetic screening of 200 genes related to inherited cardiomyopathies. Definite/moderate gene association with DCM and Arrhythmogenic Cardiomyopathy was based on the ClinGen framework. Variant prioritization was carried out using American College of Medical Genetics and Genomics rules. Correlation with histopathologic findings of the endomyocardial biopsy and family history was appraised.

Results

Twenty of the 89 suspected myocarditis patients (22%) carried a P/LP variant in cardiac-related genes: 8 in Titin, 3 in Myosin Heavy Chain 7, 2 in Desmoplakin, 2 in Lamin A/C; and Troponin T2, Filamin-C, Myosing Binding Protein C3, Desmin and Sodium Voltage-Gated Channel Alpha Subunit 5 carried one variant each. A re-analysis of the EMBs revealed that 82% of patients showed cardiomyopathy-like features at first histologic findings, with fibrosis in the myocardium and DCM-like phenotype at the second EMB. Further, 13 of the genotype-positive patients referred positive family history for cardiomyopathy and/or sudden cardiac death, whereas only 7 genotype-negative patients declared family history, showing a significant difference among both groups (p-value<0,0001).

Conclusion

The prevalence of P/LP variants in inflammatory cardiomyopathy/myocarditis patients is 22%, most of them associated with DCM. Cardiomyopathy-like features were already observed at the first EMB during the histologic re-evaluation in the majority of genotype-positive patients, and among them, high frequency of positive family history was observed. These findings suggest that genotype-positive inflammatory cardiomyopathy/myocarditis affected patients should be deeply clinically evaluated in order to guarantee an appropriate management for them and their families.
Left ventricular early diastolic strain rate and cardiovascular outcome in patients with left ventricular non-compaction phenotype
Authors: Anwer S , Gremminger M , Marchetti A U , Winkler N E , Wilzeck V , Gruner C , Tanner F C
Published: November 2023

Introduction

Speckle-tracking echocardiography is an increasingly important tool for assessing left ventricular non-compaction phenotype (LVNC). This study aims to analyse left ventricular early diastolic strain rate (eSR) in LVNC and explore its association with CV outcome during long-term follow-up.

Methods

Fifty-nine patients meeting prespecified criteria were included from our prospective LVNC cohort. eSR was determined using TomTec ImageArena (Figure A). A combined endpoint (cardiovascular events) was defined including atrial flutter/fibrillation, sustained ventricular arrhythmias, aborted cardiac arrest, and cardiovascular mortality.

Results

Baseline characteristics were comparable between patients reaching the endpoint (16 [27%]) and those without (43 [73%]) except for a higher prevalence of ischemic heart disease in the former (event group: 13%; no-event group: 2%; P=0.019). In the event group, there was a non-significant tendency for a lower LVEF (38 [26–56]% vs 51 [43–56]%; P=0.091) and LVGLS (-12.3 [-16.3 to -9.7]% vs -15.2 [-17.7 to -12.8]%; P=0.111). In contrast, eSR was significantly lower in the event group (0.45 [0.30–0.65]s-1 vs 0.70 [0.39–0.93]s-1; P=0.018; Figure B). Patients with an eSR ≤ 0.70 s-1 (ROC AUC 70%; P=0.005) exhibited a lower event-free probability in Kaplan-Meier survival analysis (P=0.001; Figure C). Inclusion of eSR improved the fitness (ꭓ2) of a multivariable logistic regression model for clinical characteristics (age, gender, and NC:C ratio; Figure D), while LVEF and LVGLS did not (Table). This improvement in ꭓ2 by eSR was significant (ANOVA P=0.033), while that by LVEF or LVGLS was not (P=0.302 and 0.152, respectively).

Conclusions

eSR was lower in LVNC patients with events, differentiated those with events from those without, and was associated with a higher risk of events during long-term follow-up. Outcome association of eSR was independent of age, gender, and NC:C ratio and improved their event prediction. eSR has potential value for functional characterization and outcome prediction in LVNC.
Right ventricular global longitudinal strain is associated with cardiovascular outcome in left ventricular non-compaction phenotype
Authors: Anwer S , Marchetti A U , Winkler N E , Gremminger M , Wilzeck V , Gruner C , Tanner F C
Published: November 2023

Introduction

Speckle-tracking echocardiography is an increasingly important tool for assessing left ventricular non-compaction (LVNC) phenotype. This study aims to analyse right (RV) and left (LV) ventricular global longitudinal strain (GLS) in patients with LVNC and explore their association with CV outcome during long-term follow-up.

Methods

From our prospective LVNC cohort study, 40 patients were identified with a comprehensive echocardiographic examination including strain analysis of both ventricles. Strain was determined using TomTec ImageArena v.4.6. A combined endpoint (CV event) was defined to include: atrial flutter/fibrillation, sustained ventricular arrhythmias, cardiac syncope, thromboembolic event, heart failure progression, aborted cardiac arrest, cardiovascular death or heart transplantation.

Results

Over a median follow-up duration of 8 [6–10] years, 23 (58%) of the patients experienced one or more CV event (event group); while the rest (17 [42%]) did not (no event group). Baseline clinical characteristics of the two groups were comparable except for a significantly older age (P<0.01) and a higher BMI (P=0.033) in the event group. RVGLS (Figure 1) was significantly lower in the event group (-13.9[-17.1 – -10.3]%) compared to no-event group (-17.3[-18.8 – -15.1]%, P=0.019). While LVGLS did not show a significant difference (P=0.112), LVEF was significantly lower (P=0.011) in the event group. Other echocardiographic parameters were comparable between the groups. RVGLS > -14.3% (sens. 61%, spec. 88%, AUC 72%; P = 0.010) was applied as cut-off to identify patients with a higher risk of CV events during follow-up. Kaplan-Meier curves revealed a higher probability of CV events when RVGLS was > -14.3% (ꭓ2 = 10.28, P = 0.001; Figure 2). Univariable regression models showed that RVGLS (HR 1.10; P = 0.013), LVGLS (HR 1.23; P = 0.045), and LVEF (HR 0.95; P = 0.005) were associated with an increased risk of CV events. The association of RVGLS (OR 1.19, P = 0.047) remained independent of LV GLS and LVEF in a multivariable logistic regression analysis. When RVGLS was included to the LV function model, a significant improvement was noted (ꭓ2 from 7.31 to 11.58; ANOVA P = 0.009).

Conclusions

RVGLS differentiated LVNC patients suffering a CV event from those who did not and provided incremental value to the association of LV function (LVEF and LVGLS) with an increased risk of CV events. These findings highlight the potential value of RVGLS for evaluating long-term outcome during follow-up of LVNC patients.
The challenge of risk stratification in hypertrophic cardiomyopathy: clinical, genetic and imaging insights from a quaternary referral centre
Authors: Paratz E , Gutman S , Stub D , La Gerche A , Mariani J , Taylor A , Ellims A
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD).

Methods

Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest.

Results

380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p=0.0041), unexplained syncope (33.3% vs 9.4%, p=0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p<0.0001), increased septal thickness (21.5 vs 17.5mm, p=0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p=0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p=0.0223).

Conclusion

This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Utilising newer markers such as cardiac MRI and genetic findings may assist future risk refinement.
Atrial fibrillation in patients with hypertrophic cardiomyopathy
Authors: Zoerner C R , Pallisgaard J L , Schjerning A M , Jensen M K , Toennesen J , Riis-Vestergaard L D , Middelfart C , Rasmussen P V , Gislason G , Hansen M L
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) is associated with complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms and increases the risk of stroke. Little is known on which factors contribute to the development of AF in these patients.

Purpose

To determine the incidence of AF in Danish HCM patients and identify risk factors that increase risk of AF.

Methods

Using Danish national registers all patients without previous AF, aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM and incident AF was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidence of AF was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account.

Results

A total of 3,200 HCM patients without prevalent AF were included, median age was 66 years (IQR 55-77) and 48% were female. During the study period, 477 (15%) patients were diagnosed with incident AF. The risk of developing AF was equal between genders and average time from HCM diagnosis to debut of AF was 1260 days. Risk of AF development was increased for patients with prevalent ischemic heart disease (HR 1.33, CI [1.08 – 1. 63]) and hypertension (HR 1.34, CI [1.11 – 1. 63]) as well as for patients classifies as obstructive HCM at diagnosis (HR 1.27, CI [1.06 – 1. 53]). Following AF diagnosis, prescription with oral anticoagulants and antiarrhythmic medication increased markedly.

Conclusion

AF is a common complication in HCM. Patients with obstructive HCM, hypertension and ischemic heart disease were at increased risk of developing AF.Figure 1:CI of AF by genderFigure 2:HR for AF developement
Mechanisms of adaptation to high intensity exercise in hypertrophic cardiomyopathy
Authors: Basu J , Ricci P , Maclachlan H , Miles C , Bhatia R , Parry-Williams G , Sharma S , Tome M , Nikoletou D , Papadakis M , O'Driscoll J
Published: November 2023

Background

Many individuals with hypertrophic cardiomyopathy (HCM) demonstrate exercise limitation. For a proportion this may be related to their overall cardiorespiratory fitness influenced by physical activity habits, body mechanics, or habitus. In others there is evidence of central and/or peripheral pathophysiology. However, some individuals with HCM demonstrate favourable adaptation to exercise. In the SAFE-HCM study, participants who underwent 12 weeks of high intensity exercise showed significant improvement in exercise indices including peak VO2, VO2/kg at anaerobic threshold (AT), time to AT, and overall exercise time compared to a usual care group.

Purpose

There have been no studies investigating the mechanistic adaptation(s) to exercise in HCM. This sub-study aimed to identify whether the observed improvements in exercise indices were attributable to central or peripheral adaptation.

Methods

Eighty patients with HCM (45.7±8.6 years) underwent baseline clinical, quality of life and psychological assessment. Individuals were randomised to a 12-week high intensity exercise programme (n=40) or usual care (n=40). Baseline evaluation was repeated at 12 weeks. The Fick equation (oxygen uptake (VO2) = cardiac output (CO) X (arterial-venous oxygen content (a-vO2 difference)) was used to assess whether central and/or peripheral adaptation was responsible for observed improvements. 2D speckle tracking imaging was utilised to calculate left ventricular longitudinal strain from the apical 2-, 3- and 4 chamber views (EchoPAC, V202, GE Healthcare).

Results

12-weeks of high intensity exercise training produced a statistically significant increase in CO (1.1±0.4 L/min, CI (0.2,2.0), p=0.016) compared with the usual care group. There was no difference in the change in a-vO2 difference between groups (p=0.682) suggesting central adaptation to high intensity exercise. This was driven by an increase in stroke volume (SV) (6.1±3.0ml, CI (0.1,12.2), p=0.047) rather than an increase in heart rate (0.6±3.6 bpm, CI (-6.6,7.7), p=0.874). However, there was no change in resting myocardial deformation to account for the observed improvement in CO. Analysis of strain data demonstrated no difference in resting regional 4Ch (-0.7±0.6, CI (-1.9, 0.5), p=0.270) 3Ch (-1.1±0.9, CI (-2.8, 0.6), p=0.201), 2Ch (-1.3±0.9, CI (-3.1, 0.5), p=0.162) or average global longitudinal strain (0.9±0.6, CI (-2.2,0.3), p=0.144) between groups at 12 weeks.

Conclusion

Favourable central adaptations, predominantly driven by an increase in SV, enable improvements in exercise capacity following a high intensity exercise programme. Further studies are required to understand the physiological processes underlying this adaptation including assessment of myocardial deformation at peak exercise
Genotipe-phenotype correlation in alpk3 null variants. an extended analysis
Authors: Garcia Hernandez S , De La Higuera Romero L , Fernandez X , Perez Barbeito M , Cazon Varela L , Peteiro Deben R , Gomez Diaz I , Valverde Gomez M , Amor Salamanca A , Cardenas I , Sanchez Flores M , Cabrera D , Ortiz-Genga M , Ochoa J P
Published: November 2023

Introduction

ALPK3 null variants (ALPK3nv) in simple heterozygosis represent an established and emerging genetic cause for hypertrophic cardiomyopathy. Some studies have indicated that this genetic substrate would be associated with a disease of late-onset disease and incomplete penetrance.

Purpose

To perform an extended genotype-phenotype correlation analysis with respect to simple heterozygous ALPK3nv carriers, focusing on age at diagnosis, maximum wall thickness and survival analysis, performed on the largest available released cohort to date.

Methods

ALPK3 gene was included in an extended NGS panel in 16,780 probands from a reference multicentric genetic laboratory, of whom 6,505 were referred with a HCM phenotype. We collected a composite cohort of ALPK3nv (considering frameshift, nonsense and splice-site predicted frameshift variants), including index and familial cases referred to this laboratory, but also cases reported in the literature. Phenotypic behavior was analyzed, mainly considering age at diagnosis, maximum LV wall thickness, and a composite of events (heart failure and arrhythmia-related endpoints).

Results

A heterozygous ALPK3 null variant was identified in 110 probands out of 6,505 index cases diagnosed with HCM in our center (1.7% of HCM cases). For genotype-phenotype analysis, in total 189 heterozygous carriers were included, considering relatives and cases from the literature; 21 carriers had biallelic involvement (were homozygous or compound heterozygous for two ALPK3Knv).

Among ALPK3nv heterozygous carriers, mean age at diagnosis was 53.4 (±15.2) years; mean left ventricular thickness was 17.7 (±4.9) mm, and morphological profile was mainly apical (42%) and/or concentric (26%). Males tended to be diagnosed at an earlier age than females (median age of diagnosis was 56 vs 71 years, respectively, p <0.01). Five events were observed in this group (four males and one female) all of them related to heart failure, and occur in carriers older than 45 years. The clinical profile was drastically different in cases with biallelic involvement, with a mean age at diagnosis of 22.2±9.3, mean LV wall thickness of 24 mm (±8.6), with LV dysfunction observed in 25%. Nine events were observed in this group, also mostly associated with HF (70%).

Conclusions

ALPK3 null variants in simple heterozygosis can explain 1.7% of HCM. They were associated with late-onset disease, especially in females, predominance of apical and/or concentric forms, and a phenotype that was not particularly severe, both morphologically and in terms of survival.
Risk stratification in patients with structurally normal hearts: does fibrosis type matter?
Authors: Gil K , Mikrut K , Mazur J , Lowery Black A , Vien T , Smart S , Zareba K M
Published: November 2023

Background

The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear.

Purpose

The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR) – both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV) – in patients with structurally normal hearts.

Methods

Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated.

Results

In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall (Figure 1B-C)/subepicardial LGE (Figure 1D) was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients (Figure 1A). In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p=0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p=0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p=0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p=0.66)(Figure 2). There was no significant association between arrhythmic outcomes and LGE (p=0.60) or ECV (p=0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p=0.009).

Conclusion

Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool.
Does aetiology of dilated cardiomyopathy impact the outcome in Eastern Europe?
Authors: Dziewiecka E , Wisniowska-Smialek S , Winiarczyk M , Karabinowska-Malocha A , Robak J , Kaciczak M , Baranowski F , Rubis P
Published: November 2023

Introduction

There are regional variations (West vs. East vs. North vs. South) in aetiology and outcomes in patients with cardiomyopathies according to EORP Registry. However, those preliminary observations have not been systematically verified. Here we report on the large cohort of dilated cardiomyopathy (DCM) patients managed in a tertiary centre in Eastern Europe.

Purpose

Analysis of all-cause mortality in DCM patients with different aetiology.

Methods

500 DCM patients (aged 53.1±13.6 years, 81% male, LVEF 26.6±10.4%, LVEDd 65.9±10.3mm, symptoms duration 38.6±61.2 months) from 2010-2021 with complete baseline and follow-up data were included retrospectively. DCM aetiology was diagnosed according to medical documentation as: idiopathic, inflammatory, toxic: alcohol-induced or other (including chemotherapy and drug-induced), arrhythmic and familial or genetic (ref genetic). After mean follow-up (FU) of 45.6±31.0 months, the all-cause mortality and composite endpoint (all-cause mortality, heart transplant – HTX, left ventricle assist device implantation - LVAD) were assessed.

Results

Out of 500 DCM patients no clear aetiology was found in 41% of patients (idiopathic DCM). The most common was inflammatory DCM, followed by alcohol-induced, arrhythmic, and genetic DCM (Figure 1-A). The least common was toxic DCM (18 - after chemotherapy, 2 – drug-induced).

During FU there were 97 (19%) patients with the following events: 88 (18%) patients died, 7 (1%) had LVAD and 15 (3%) had HTX (Figure 1-B). Statistically, all groups did not differ in terms of events (all p>0.05), however on the Kaplan-Meier plot patients with toxic DCM (chemotherapy or drug-induced) had the worst outcome while patients with inflammatory DCM had the best outcome during 6-years FU (Figure 1-C, 1-D).

Conclusion

More than one-third of DCM patients were diagnosed with idiopathic DCM. Toxic DCM was the second most prevalent aetiology and was diagnosed in nearly a quarter of patients. Alcohol-induced DCM was present in every fifth of patients. Although statistically no difference in outcome was found, according to Kaplan-Meier curves, patients with inflammatory DCM have the best prognosis and those with chemotherapy- or drug-induced – the worst.Figure 1.