Histopathological Features and Protein Markers of Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a heritable heart muscle disease characterized by syncope, palpitations, ventricular arrhythmias and sudden cardiac death (SCD) especially in young individuals. It is estimated to affect 1:5,000 individuals in the general population, with >60% of patients bearing one or more mutations in genes coding for desmosomal proteins. Desmosomes are intercellular adhesion junctions, which in cardiac myocytes reside within the intercalated disks (IDs), the areas of mechanical and electrical cell-cell coupling. Histologically, ACM is characterized by fibrofatty replacement of cardiac myocytes predominantly in the right ventricular free wall though left ventricular and biventricular forms have also been described. The disease is characterized by age-related progression, vast phenotypic manifestation and incomplete penetrance, making proband diagnosis and risk stratification of family members particularly challenging. Key protein redistribution at the IDs may represent a specific diagnostic marker but its applicability is still limited by the need for a myocardial sample. Specific markers of ACM in surrogate tissues, such as the blood and the buccal epithelium, may represent a non-invasive, safe and inexpensive alternative for diagnosis and cascade screening. In this review, we shall cover the most relevant biomarkers so far reported and discuss their potential impact on the diagnosis, prognosis and management of ACM.

171 Right ventricular free wall longitudinal strain (RVFWSL): a new outcome predictor in patients candidate for TAVI

Aims Right ventricular systolic dysfunction is considered an outcome predictor in various cardiac diseases, sometimes stronger than ejection fraction (EF). We assume that right ventricular dysfunction, calculated with echocardiography in patients candidate for trans-catheter aortic valve implantation (TAVI), could be an outcome predictor. To evaluate the prognostic value of pre-TAVI right ventricular free wall longitudinal strain (RVFWSL) in patients with severe aortic stenosis undergoing TAVI. Methods and results Retrospective analysis of 100 patients underwent transfemoral TAVI in our hospital from January 2015 to September 2019, with at least a pre-TAVI and post-TAVI echocardiography. For each patients we collected clinical and echo data before and after TAVI and during the follow-up; we measured RVFWSL off-line at the same time. We considered the value of [23.3]% the cut-off of normality for RVFWSL. The primary endpoint was a composite of death from any cause and hospitalization for heart failure. The median age of the patients was 81 years (79–83) and EF was preserved in most patients (median: 56%, 55–58.28%). At a median follow-up of 1023 days (630–1387), the univariate analysis demonstrated a predictive of a reduced RVFWSL before TAVI ( < [23.3]%, P = 0.015) and EF < 50% (P = 0.014). Cox regression analysis found that pre-TAVI reduced RVFWSL (HR: 2.875, CI 95%: 1.113–7.425; P = 0.03) and EF < 50% (HR: 2.511, CI 95%: 1.07–5.892; P = 0.03) were independently associated with composite endpoint of the study. Moreover, a reduced EF associated with RVFWSL < [23.3]% had an incremental value in predicting the outcome (P = 0.021). Conclusions Among patients with severe aortic stenosis undergoing TAVI, a reduced pre-implant RVFWSL is able to predict long-term outcome.

Prognostic value of right ventricular native T1 mapping in pulmonary arterial hypertension

Background Right ventricular function is an important prognostic marker for pulmonary arterial hypertension. Native T1 mapping using cardiovascular magnetic resonance imaging can characterize the myocardium, but accumulating evidence indicates that T1 values of the septum or ventricular insertion points do not have predictive potential in pulmonary arterial hypertension. We aimed to elucidate whether native T1 values of the right ventricular free wall (RVT1) can predict poor outcomes in patients with pulmonary arterial hypertension. Methods This retrospective study included 30 patients with pulmonary arterial hypertension (median age, 45 years; mean pulmonary artery pressure, 41±13 mmHg) and 16 healthy controls (median age, 43 years) who underwent native T1 mapping. RVT1 was obtained from the inferior right ventricular free wall during end systole. Results Patients with pulmonary arterial hypertension had significantly higher native RVT1 than did controls (1384±74 vs. 1217±57 ms, p<0.001). Compared with T1 values of the septum or ventricular insertion points, RVT1 correlated better with the effective right ventricular elastance index (R = −0.53, p = 0.003), ventricular-arterial uncoupling (R = 0.46, p = 0.013), and serum brain natriuretic peptide levels (R = 0.65, p<0.001). Moreover, the baseline RVT1 was an accurate predictor of the reduced right ventricular ejection fraction at the 12-month follow-up (delta -3%). RVT1 was independently associated with composite events of death or hospitalization from any cause (hazard ratio = 1.02, p = 0.002). Conclusions RVT1 was predictive of right ventricular performance and outcomes in patients with pulmonary arterial hypertension. Thus, native T1 mapping in the right ventricular free wall may be an effective prognostic method for pulmonary arterial hypertension.

Mitral and tricuspid annulus disjunction frequently coexist

Background Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus, frequently found in patients with high-risk arrhythmogenic mitral valve prolapse syndrome. It is unknown whether the annulus disjunction extends to the right side of the heart as tricuspid annulus disjunction (TAD), and whether it is associated with right ventricular electrical instability. Purpose We aimed to explore the presence of TAD, and if extended annulus disjunction was associated with ventricular arrhythmias. Methods We included patients with previously described MAD assessed by cardiac magnetic resonance imaging (CMR) in an ambispective cohort study. MAD and TAD was defined as ≥1 mm separation between the respective atrial wall-valve leaflet junction and the top of the ventricular myocardium. TAD was assessed in the lateral and inferior right ventricular free wall by means of the 4-chamber and right ventricular 2-chamber views, respectively. MAD circumference was assessed by a CMR study protocol with six left ventricular long axis views separated by 30 degrees. Mitral valve prolapse was defined as ≥2 mm superior displacement of any part of the mitral leaflets beyond the mitral annulus. Ventricular arrhythmias were defined as aborted cardiac arrest or non-sustained/sustained ventricular tachycardias recorded by electrocardiogram (ECG), stress ECG or Holter monitoring. Results We included 92 patients with MAD (62% female, age 47±16 years, 71% mitral valve prolapse). TAD was found in 48 (52%) patients, both in the lateral (n=40, 83%) and inferior (n=30, 63%) right ventricular free wall. Patients with TAD were older (age 51±16 years vs. 43±14 years, p=0.01), had greater MAD circumference (168±56° vs. 117±62°, p=0.001) and greater MAD distance (9.2±2.9 mm vs. 6.4±2.8 mm, p&lt;0.001). Additionally, patients with TAD had more frequently mitral valve prolapse (40 patients [85%] vs. 25 patients [57%], p=0.003), whereas similar frequency of bileaflet prolapse (17 patients [39%] vs. 10 patients [39%], p=0.99). Ventricular arrhythmias had occurred in 38 (41%) patients, who were younger (age 40±14 years vs. 52±15 years, p&lt;0.001) and had less frequently TAD (14 patients [37%] vs. 34 patients [63%], p=0.01; univariate odds ratio 0.34 [0.15–0.81], p=0.02). However, TAD was not associated with ventricular arrhythmias when adjusted for age (multivariate odds ratio 0.46 [0.18–1.15], p=0.10). Conclusions TAD by CMR was highly prevalent in patients with MAD and was a marker of severe annulus disjunction and mitral valve prolapse. TAD was not associated with more ventricular arrhythmias. This novel marker warrants further research to explore the clinical implications of right-sided annulus disjunction. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council

Tricuspid chordal rupture following stab injury: a case of successful repair

We report a case of a 32-year-old male patient who sustained an isolated stab injury to the left chest wall. He was initially treated with emergency surgery for right ventricular free wall rupture, with an uneventful postoperative course. During follow-up, the patient complained of exercise intolerance and dyspnea on effort. Transthoracic echocardiography (TTE) demonstrated a previously undiagnosed severe tricuspid regurgitation due to flail of the anterior leaflet and a ruptured chorda. A redo operation was scheduled, and the valve was successfully repaired, with different techniques employed. This case highlights the importance of careful clinical evaluation of victims of chest penetrating trauma and how early diagnosis of hidden valvular lesions might increase the odds of valve repair. It also demonstrates the clover technique as a valuable technique in the correction of traumatic tricuspid regurgitation.