A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. OBJECTIVES: The study aimed to identify predictors of end­stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. PATIENTS AND METHODS: A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin­3 [Gal­3], extracellular matrix metalloproteinases [MMP­2 and MMP­9], N­terminal pro-B­type natriuretic peptide [NT­proBNP], and high­sensitivity troponin T [hs­TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter­defibrillator intervention. RESULTS: During the median (interquartile range) follow­up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT­proBNP concentration (≥890.3 pg/ml), greater right ventricular end­diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. CONCLUSIONS: An NT­proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

Implantable cardiac defibrillator events in patients with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a risk of sudden cardiac death. Optimal risk stratification is still under debate. The main purpose of this long-term, single-centre observation was to analyse predictors of appropriate and inappropriate implantable cardioverter-defibrillator (ICD) interventions in the population of patients with ARVC with a high risk of life-threatening arrhythmias. METHODS: The study comprised 65 adult patients (median age 40 years, 48 men) with a definite diagnosis of ARVC who received ICD over a time span of 20 years in primary (40%) or secondary (60%) prevention of sudden cardiac death. The study endpoints were first appropriate and inappropriate ICD interventions (shock or antitachycardia pacing) after device implantation. RESULTS: During a median follow-up of 7.75 years after ICD implantation, nine patients died and six individuals underwent heart transplantation. Appropriate ICD interventions occurred in 43 patients (66.2%) and inappropriate ICD interventions in 18 patients (27.7%). Multivariable analysis using cause-specific hazard model identified three predictors of appropriate ICD interventions: right ventricle dysfunction (cause-specific HR 2.85, 95% CI 1.56 to 5.21, p<0.001), age <40 years at ICD implantation (cause-specific HR 2.37, 95% CI 1.13 to 4.94, p=0.022) and a history of sustained ventricular tachycardia (cause-specific HR 2.55, 95% CI 1.16 to 5.63, p=0.020). Predictors of inappropriate ICD therapy were not found. Complications related to ICD implantation occurred in 12 patients. CONCLUSIONS: Right ventricle dysfunction, age <40 years and a history of sustained ventricular tachycardia were predictors of appropriate ICD interventions in patients with ARVC. The results may be used to improve risk stratification before ICD implantation.

Pathogenic variants in plakophilin-2 gene (PKP2) are associated with better survival in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is mainly caused by mutations in genes encoding desmosomal proteins. Variants in plakophilin-2 gene (PKP2) are the most common cause of the disease, associated with conventional ARVC phenotype. The study aims to evaluate the prevalence of PKP2 variants and examine genotype-phenotype correlation in Polish ARVC cohort. All 56 ARVC patients fulfilling the current criteria were screened for genetic variants in PKP2 using denaturing high-performance liquid chromatography or next-generation sequencing. The clinical evaluation involved medical history, electrocardiogram, echocardiography, and follow-up. Ten variants (5 frameshift, 2 nonsense, 2 splicing, and 1 missense) in PKP2 were found in 28 (50%) cases. All truncating variants are classified as pathogenic/likely pathogenic, while the missense variant is classified as variant of uncertain significance. Patients carrying a PKP2 mutation were younger at diagnosis (p = 0.003), more often had negative T waves in V1-V3 (p = 0.01), had higher left ventricular ejection fraction (p = 0.04), and were less likely to present symptoms of heart failure (p = 0.01) and left ventricular damage progression (p = 0.04). Combined endpoint of death or heart transplant was more frequent in subgroup without PKP2 mutation (p = 0.03). Pathogenic variants in PKP2 are responsible for 50% of ARVC cases in the Polish population and are associated with a better prognosis. ARVC patients with PKP2 mutation are less likely to present left ventricular involvement and heart failure symptoms. Combined endpoint of death or heart transplant was less frequent in this group.

Quality and utility of [123I]I-metaiodobenzylguanidine cardiac SPECT imaging in nondiabetic postinfarction heart failure patients qualified for implantable cardioverter defibrillator.

OBJECTIVE: Impaired cardiac adrenergic activity has been demonstrated in heart failure (HF) and in diabetes mellitus (DM). [123I]I-metaiodobenzylguanidine (MIBG) enables assessment of the cardiac adrenergic nervous system. Tomographic imaging of the heart is expected to be superior to planar imaging. This study aimed to determine the quality and utility of MIBG SPECT in the assessment of cardiac innervation in postinfarction HF patients without DM, qualified for implantable cardioverter defibrillator (ICD) in primary prevention of sudden cardiac death. METHODS: Consecutive patients receiving an ICD on the basis of contemporary guidelines were prospectively included. Planar MIBG studies were followed by SPECT. The essential analysis was based on visual assessment of the quality of SPECT images ("high", "low" or "unacceptable"). The variables used in the further analysis were late summed defect score for SPECT images and heart-to-mediastinum rate for planar images. MIBG images were assessed independently by two experienced readers. RESULTS: Fifty postinfarction nondiabetic HF subjects were enrolled. In 13 patients (26%), the assessment of SPECT studies was impossible. In addition, in 13 of 37 patients who underwent semiquantitative SPECT evaluation, the assessment was equivocal. Altogether, in 26/50 patients (52%, 95% confidence interval 38-65%), the quality of SPECT images was unacceptable or low and was limited by low MIBG cardiac uptake and by comparatively high, interfering MIBG uptake in the neighboring structures (primarily, in the lungs). CONCLUSIONS: The utility of MIBG SPECT imaging, at least with conventional imaging protocols, in the qualification of postinfarction HF patients for ICD, is limited. In approximately half of the postinfarction HF patients, SPECT assessment of cardiac innervation can be impossible or equivocal, even without additional damage from diabetic cardiac neuropathy. The criteria predisposing the patient to good-quality MIBG SPECT are: high values of LVEF from the range characterizing the patients qualified to ICD (i.e., close to 35%) and left lung uptake intensity in planar images comparable to or lower than heart uptake.

Transcatheter pulmonary valve implantation in 100 patients: a 10-year single-center experience.

Introduction: Transcatheter pulmonary valve implantation (TPVI) is a non-surgical method of treatment for patients with right ventricular outflow tract (RVOT) dysfunction after surgical repair of congenital heart defects (CHD). Aim: To evaluate the long-term results of TPVI performed in a single center.Material and methods: Over 10 years, TPVI was performed in 100 patients (mean age: 26.4 ±8.1 years), using Melody Medtronic or Sapien Edwards valves. Results: The initial success rate of TPVI was 93%. In 7 cases (5 urgent), a switch to surgical intervention was necessary due to periprocedural complications (all patients survived). Following TPVI, none of the 93 patients had severe pulmonary regurgitation. The pulmonary gradient decreased from 49.0 ±37.8 before to 27.6 ±14.9 mm Hg directly after TPVI (p < 0.0001). Right ventricular end-diastolic volume decreased, while NYHA class and pVO2 uptake significantly improved in 1 year after TPVI. Freedom from reintervention was 100% in 1 year. Freedom from serious adverse events was 86% in mean 5.5 years of observation. The main reason for reintervention was infective endocarditis (IE) (1.6% patients/year). Increased risk of IE was associated with severe PS before valve implantation and the suboptimal result of TPVI. The incidence of IE seems to be lower in patients treated permanently with antiplatelet therapy (1.8% vs. 0.9% patients/year, NS). Conclusions: TPVI is a safe and effective method of treatment in patients with RVOT dysfunction after surgical correction of CHD. To achieve a good outcome, precise patient selection and rigorous IE prevention are necessary.

Ablation of atrial tachyarrhythmias late after surgical correction of tetralogy of Fallot: long-term follow-up.

BACKGROUND: After the surgical correction of tetralogy of Fallot, surgical scars and natural obstacles form pathways capable of supporting an atrial tachyarrhythmia (AT). Radiofrequency (RF) ablation is effective, although the few studies published on this topic had relatively short follow-up periods. AIM: The aims of the study were to evaluate the acute and long-term effects of RF ablation of AT and examine the charac-teristics of arrhythmia recurrence. METHODS: Tetralogy of Fallot patients (n = 16, age 44.7 ± 10.7 years) referred for ablation of ATs, appearing 25.7 ± 9.6 years after repair, were studied. RESULTS: Twenty-five ATs were ablated, including 16 cavo-tricuspid isthmus atrial flutters (CTI-AFLs) and nine intraatrial reentrant tachycardia (IART). In one patient with paroxysmal atrial fibrillation (PAF), pulmonary vein isolation was also performed. Ten patients had permanent, and six had paroxysmal arrhythmia prior to the first ablation. Four patients had PAF. Regardless of the type of first ablated arrhythmia, all 16 patients required CTI-AFL ablation. The effectiveness of the first RF ablation reached 88%. The acute efficacy of RF ablation was 100% for CTI-AFL and 78% for IART. Long-term follow-up was possible in 15 out of 16 patients (mean follow-up 68.8 ± 36.6 months). Four patients were free of sustained arrhythmia, nine (60%) had AF. After the last RF ablation, an episode suggestive of CTI-AFL/IART was documented only in one patient. CONCLUSIONS: Ablation of CTI-AFL/IART in tetralogy of Fallot patients is safe and effective. AF was observed in most patients during the long-term follow-up. Regardless of the type of the first ablated arrhythmia, all patients required CTI-AFL ablation.

A unique case of systemic thromboembolism in a patient with arrhythmogenic right ventricular cardiomyopathy.

We report a case of a 37-year-old woman with arrhythmogenic right ventricular cardiomyopathy (ARVC), after implantation of a cardioverter-defibrillator (ICD), who was admitted to our hospital because of focal infarctions in the right kidney and in the spleen. Echocardiography showed thrombi on the ICD electrode and the presence of patent foramen ovale. Patent foramen ovale was successfully closed by septal occluder. To our knowledge it is the first ever case report of paradoxical thromboembolism in a patient with ARVC.

Isolated ventricular noncompaction mimicking arrhythmogenic right ventricular cardiomyopathy--a study of nine patients.

BACKGROUND: Isolated ventricular noncompaction is considered to predominantly affect the left ventricle. It is characterized by increased left ventricular wall thickness and deep intertrabecular recesses with to-and-fro blood flow that remains in continuity with the ventricular flow. Aim of the study was to present a group of patients with isolated noncompaction of both ventricles mimicking arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Reported group consisted of 9 pts initially diagnosed with ARVC (mean age 37.9 y, 7 male), who underwent basic clinical evaluation. CMR was performed in 8 pts, cardiac catheterization in 2 pts and endomyocardial biopsy in 2 pts. Mean age at presentation of first symptoms was 23.5 y (5-44 y). Heart failure symptoms were observed in 4 pts, atrial fibrillation in 3 pts, ventricular tachycardia in 2 pts (polymorphic--in 2 pts) and syncope in 3 pts. Final diagnosis of noncompaction was established according to generally accepted criteria. RESULTS: Morphologic and/or functional changes in the right ventricle were seen in 9 pts (100%): enlargement and hypertrabeculation of the right ventricle in all pts, global hypokinesis in 4 pts, focal wall motion abnormalities and/or bulges typical for ARVC in 5 pts. Two pts had significant tricuspid regurgitation. Endomyocardial biopsy (2 pts) showed abnormal thick endocardium, interstitial fibrosis, myocardial damage and lymphocyte infiltration. CONCLUSIONS: 1) Noncompaction of ventricular myocardium should be considered during the evaluation of right ventricular cardiomyopathies with excessive trabeculation. 2) In problematic cases Task Force criteria for ARVC should be used to improve the accuracy of assessment.

Aortic regurgitation and unusual diastolic mitral regurgitation.

In patients with infective endocarditis affecting the aortic valve, a secondary involvement of subaortic structures may occur in a mechanism of direct extension or as a result of an infected jet of aortic regurgitation striking the ventricular surfaces of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet (AML). We present a 29-year-old male with infective endocarditis of the bicuspid aortic valve, who developed a secondary infection of the subaortic tissues complicated by a perforation of the AML. Echocardiographic examination revealed not only systolic, but also diastolic mitral regurgitation.

Economic evaluation of screening for familiar form of arrhythmogenic right ventricular cardiomyopathy in Poland.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease associated with fibrofatty tissue replacement in heart muscle leading to arrhythmia, heart failure or sudden death (SCD) often being the first manifestation in probands. At least 50% of cases of ARVC are inherited. AIM: To evaluate costs and cost-effectiveness of diagnosis of the disease in asymptomatic relatives in Poland. METHODS: 239 asymptomatic subjects (mean age 35 years, 120 male) belonging to 42 families affected with ARVC were examined between May 2003 and May 2005. The costs of outpatient visits and additional diagnostic tests were included. Payer perspective was used. RESULTS: In all individuals ECG and transthoracic echocardiography were performed. Magnetic resonance imaging and signal-averaged ECG were performed in 35 patients suspected of having ARVC. The diagnostic criteria for ARVC were fulfilled in 29 patients and 57 subjects were recognised borderline. Total costs of screening amounted to 71 090 PLN (approximately 20,000 euro). The average cost per one case of detected ARVC was 2451 PLN (approximately 680 euro). CONCLUSIONS: Costs of early detection of ARVC in individuals with a family history of the disease in Polish settings are low. Due the avilability of primary prevention of SCD the family screening in asymptomatic subjects is a cost-effective procedure.

Thromboembolic complications in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

AIMS: Incidence and clinical presentation of thromboembolic complications in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) were analysed. In reports on ARVD/C, thromboembolism is rarely mentioned. The possible risk factors are: right ventricle (RV) dilatation, aneurysms, and wall motion abnormalities. METHODS AND RESULTS: A group of 126 patients (89 male, 37 female, aged 43.6+/-14.3) with ARVD/C was retrospectively analysed for the presence of thromboembolic complications. The mean follow-up period was 99+/-64 months. Thromboembolic complications, i.e. pulmonary embolism (n=2), RV outflow tract thrombosis with severe RV failure (n=1), and cerebrovascular accident associated with atrial fibrillation (n=2) were observed in 4% of the patients. Spontaneous echogenic contrast was observed in seven patients with severe damage to RV. In four of them supraventricular arrhythmias resulting in heart failure were reported. Annual incidence of thromboembolic complications was 0.5/100 patients. CONCLUSIONS: (i) ARVD/C may be complicated by thrombosis. Annual incidence of such complications is significantly lower than reported for left ventricle failure. (ii) Anticoagulation should be used in ARVD/C patients with large, hypokinetic RV and slow blood flow. (iii) Patients with severe forms of ARVD/C, thrombus formation in the RV and/or spontaneous echocardiographic contrast are at higher risk of a poor outcome.