Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment.

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment.

Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.

Over 10 years with an implantable cardioverter-defibrillator - a long term follow-up of 60 patients.

BACKGROUND: Transvenous implantable cardioverter-defibrillators (ICD) have been implanted in Poland since 1995. As the method spreads it is important to consider its long-term benefits and disadvantages. AIM: To assess survival, efficacy and complication rate in ICD patients, who received the device more than ten years earlier. METHODS: Retrospective analysis of 60 ICD patients implanted between 1995-1999. RESULTS: There were 42 (70%) males, mean age 50.6 ± 16.4 years. In 59 patients ICD was implanted for sudden cardiac death (SCD) secondary prevention. Thirty eight patients (34 M, 63.3%) had coronary artery disease (CAD). The CAD was diagnosed in 89.5% of males and 10.5% of females (p〈 0.0001). Mean follow-up time was 75.4 ± 34.7 months. During this time 22 patients died (37%, 19 M, 3 F). Three deaths were SCD. Mean one-year mortality was 6.7%. Deaths were more frequent among males: 45.2% vs 16.7%, p〈 0.005. In CAD mortality was higher than in non-CAD patients (50% vs 13.6%, p〈 0.005). Appropriate ICD discharges in the ventricular fibrillation (VF) zone occurred in 35 (58%) patients, and in ventricular tachycardia (VT) zone - in 26 (43%) patients. Mean intervention rate per year was 3.7 for VF and 0.6 for VT. Complications occurred in 27 (45%) patients and 5 (8%) of them had no ICD intervention during follow-up. In 5 patients more than one complication was diagnosed. There were inappropriate discharges in 15 (25%) patients, 11 (18%) had electrical storm, and ICD-related infections were noted in 3 (5%) patients. During the perioperative period, lead revisions were done in 4 patients; in 3 with discharges induced by T-wave oversensing and in one with lead dislocation. Four cases of lead failure occurred during follow-up, requiring new lead implantation. In 4 patients, electrical storm (3 patients) and supraventricular tachycardia with ICD discharges (1 patient) were treated with radiofrequency ablation. Only 10 (17%) patients did not demonstrate any ICD interventions or ICD-related complications. CONCLUSIONS: 1. ICD interventions caused by malignant ventricular arrhythmias occurred in 75% patients with the device implanted more than 10 years earlier. 2. Almost a half of the analysed population suffered from complications and side effects related to implanted ICD and they were present in 8% of subjects without ICD intervention. Neither ICD interventions nor device-related adverse events were recorded in 17% of patients.

Success rate of transvenous left ventricular lead implantation for cardiac resynchronisation therapy - recent experience of a single centre.

BACKGROUND: Implantation of a left ventricular (LV) lead for cardiac resynchronisation therapy (CRT) may be challenging. Wider use of various implantation techniques increases the success rate of CRT. AIM: Short-term analysis of the success rate of transvenous LV lead implantation for CRT. METHODS: All CRT procedures performed in 2009 with first-time LV lead implantation attempt were analysed in terms of efficacy, total number of procedures, procedure and fluoroscopy time, complications, and reinterventions. Final LV lead location and the number of tested sites were analysed. Complex procedures were defined and described. RESULTS: We studied 122 patients aged 67.6 +/- 10.6 years (98 males/80%) selected for CRT. The CRT implantation was an upgrade procedure in 17 patients. Fifty-six (46%) patients had coronary artery disease and 111 (91%) patients were in NYHA class III. The mean LV ejection fraction was 27% (range 10-35%). The implantation success rate was 97.5%. There were 87 (73%) CRT-D systems implanted and 32 (27%) CRT-P systems. Mean procedure time was 118 +/- 41 min, and fluoroscopy time was 15.9 +/- 12.1 min. An optimal location of the LV lead was achieved in 107 (90%) patients. More than one LV lead sites were tested in 42 (35.3%) patients. Complex procedures were performed in 4 (3.4%) patients. Early LV lead reintervention (< 30 days) was necessary in 10 (8.4%) patients (11 procedures), and epicardial lead placement was performed in one patient. The LV lead location in the antero-lateral branch demonstrated the lowest reintervention rate (1/22, 4.5%) v. other sites (great cardiac vein: 1/8, 12.5%, lateral branches: 9/86, 10.5%, p = NS). The LV lead-related reinterventions and initial procedure failure were associated with the upgrade procedures. No serious periprocedural complications were recorded. In one patient, the CRT system was explanted due to pocket infection. One patent died three months after CRT implantation due to progressive end-stage congestive heart failure. CONCLUSIONS: 1. In a tertiary centre, CRT implantation success rate is high and implantation procedures are safe. 2. Achieved LV lead location is optimal in a vast majority of patients. 3. We noted a significant rate of early reinterventions related to LV lead dislodgement. 4. The LV lead implantation failure and reinterventions occurred more frequently in subjects with upgrade- to-CRT procedures. A similar trend was also noted in patients after cardiac surgery. 5. In selected cases, advanced techniques must be used to achieve successful CRT implantation.

Dilated cardiomyopathy with profound segmental wall motion abnormalities and ventricular arrhythmia caused by the R541C mutation in the LMNA gene.

In laminopathies cardiac involvement is common with dilated cardiomyopathy associated with atrio-ventricular block and malignant ventricular arrhythmia found in vast majority of patients. However, the specific disease course can be very different even among members of the same family which makes genotype-phenotype correlations difficult. Here we describe a 19-year-old patient with the LMNA R541C mutation and compare the course of his disease with two previously reported cases of the same molecular defect. We found that our patient shared important features with the previously described other subjects: significant LV segmental contractility defects (dyskinesis of the inferior wall and akinesis of LV apex), the presence of LBBB without atrio-ventricular block on 12-lead standard ECG and ICD requirement. The important differences between our subject and previously reported cases were early presentation (first symptoms at the age of 11 years) and early, progressive LV dilatation. We conclude that the LMNA R541C mutation should be considered not only in patients with malignant ventricular arrhythmia and LV local wall motion abnormalities, but also in classic dilated cardiomyopathy with profound segmental LV contractility defects.

Causes of redo procedures in patients with an implantable cardioverter-defibrillator--long-term follow-up results.

BACKGROUND: Implantation of a cardioverter-defibrillator (ICD) is a well-established method to prevent sudden cardiac death (SCD). Due to the expanding indications for this type of treatment and increasing survival of these patients, the ICD population is growing rapidly. AIM: To assess the rate and causes of reoperations in patients with ICD over a long-term (at least 4 years) follow-up period. METHODS: Between 1995 and 2006, an ICD was implanted in 598 patients. This study included all patients with a follow-up duration of at least 4 years and only those who underwent a repeat procedure later than 6 weeks after the index ICD implantation. RESULTS: The study group consisted of 174 patients with a mean age of 51+/-18 years who were followed for a mean of 6+/-1.7 years. Coronary artery disease (CAD) was diagnosed in 92 (53%) patients, and non-ischaemic cardiomyopathy in 82 (47%) patients. Prophylactic ICD therapy was instituted in 11 (6%) patients, whereas 163 (94%) patients received ICD for secondary prophylactics. During the follow-up period, 10 deaths occurred: 6 of all deaths (60%) in patients with CAD and 4 of all deaths (40%) in the non--ischaemic group. A total of 211 redo procedures in 139 patients were performed. Indications for repeat procedures included battery depletion in 136 patients, ICD malfunction in 37 cases, infection related to the implanted system in 5 patients, problems with leads in 19 cases, an upgrade to the dual-chamber system in 5 or to the biventricular system in 3 patients, and the revision of an ICD pocket in 6 patients. CONCLUSIONS: Repeat procedures in ICD recipients are frequent. The most common cause is battery depletion and ICD replacement indicated by a manufacturer. Improvement in ICD technology is essential to increase ICD longevity and decrease the redo-procedure rates. Patients with ICD should be regularly followed in experienced centres in order to detect ICD system failure early.