Andrea Macchione

Noninvasive Diagnosis of Electroanatomic Abnormalities in Arrhythmogenic Right Ventricular Cardiomyopathy

Background—The diagnostic reliability and pathophysiologic relevance of different noninvasive diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are undefined. We tested the association between noninvasive diagnostic criteria for ARVC and the presence of low-voltage areas (LVAs) detected at electroanatomic voltage mapping (EAM). Methods and Results—Noninvasive diagnostic criteria, including ECG, signal-averaged ECG (SAECG), and cardiac magnetic resonance (CMR) criteria, were compared with the presence and location of LVAs detected at right ventricular (RV) EAM in 17 patients (9 men) aged 50±16 years with biopsy specimen-proven ARVC. LVAs were found in 15 (88%) patients. Patients with surface ECG abnormalities showed a higher degree of RV involvement than those without ECG abnormalities (number of LVAs, 1.8±0.5 versus 0.9±0.6, respectively; P<0.01). A significant association was found between SAECG abnormalities and LVAs in the RV outflow tract (P=0.03) but not between SAECG parameters and LVAs in other RV regions. Among CMR findings, RV delayed enhancement was more significantly associated with the distribution of LVAs (free wall, P<0.01; outflow tract, P<0.01; posteroinferior wall, P=0.02). Regional RV dysfunction also showed a good correlation with LVAs, with the most significant association being found with the free wall (P=0.01), whereas RV fat infiltration at CMR was not correlated with LVAs. Conclusion—In patients with ARVC, SAECG abnormalities correlate with the presence of LVAs selectively in the RV outflow tract, whereas surface ECG abnormalities are associated with a more diffuse RV involvement. Myocardial delayed enhancement is the CMR finding more strongly associated with LVAs, thus supporting the appropriateness of its inclusion among diagnostic criteria for ARVC.

Correlation between signal-averaged ECG and the histologic evaluation of the myocardial substrate in right ventricular outflow tract arrhythmias.

Background—The differential diagnosis between idiopathic and cardiomyopathy-related right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs) is crucial. Signal-averaged ECG (SAECG) abnormalities are frequent in cardiomyopathy-related RVOT-VAs, although their pathophysiologic basis and diagnostic value in this setting are undefined. We tested the association between SAECG and the myocardial substrate underlying RVOT-VAs. Methods and Results—Twenty-four consecutive patients (median age, 50 years [42–59]; 12 men) with RVOT-VAs (10 with frequent [>1000/24 hours] premature ventricular contractions, 14 with ventricular tachycardias) underwent SAECG with 40-Hz filtering and electroanatomic mapping (EAM) with EAM-guided biopsy for characterization of the RVOT-VAs substrate. A filtered averaged QRS (fQRS) was obtained and analyzed for fQRS duration, low amplitude signal duration <40 mV (LAS40), and root-mean-square voltage in the last 40 ms of the QRS (RMS40). Standard definition of EAM scar was used. EAM-guided biopsy diagnosed ARVC in 11 (46%), myocarditis in 8 (33%), and idiopathic RVOT-VAs in 5 (21%) patients. Patients with cardiomyopathy-related RVOT-VAs had ≥1 EAM scar (median, 2 [1–2]; all with RVOT scar). EAM of patients with idiopathic RVOT-VAs was normal. Patients with cardiomyopathy-related RVOT-VAs had significantly longer fQRS (106 ms [92–132] versus 83 ms [82–84], P=0.01) and LAS40 (39 ms [36–51] versus 19 ms [18–21], P=0.02), and lower RMS40 (18 µV [9–26] versus 33 µV [32–33], P=0.04). A significant linear correlation was found between the extension (cm2) of the RVOT scar and all 3 SAECG parameters (rs=0.76, P<0.001 for the fQRSd; rs=0.73, P<0.001 for the LAS40; and rs=−0.72, P<0.001 for the RMS40). Using the established 2 of 3 criteria (ie, late potentials), SAECG diagnosed cardiomyopathy-related RVOT-VAs with high positive (100%) but low negative (38%) predictive values and missed 7 of 9 (78%) patients with RVOT scar <8 cm2. Conclusions—In patients with RVOT-VAs, abnormal SAECG parameters reflect the presence of extensive cardiomyopathic involvement of the RVOT. However, a negative SAECG does not reliably rule out cardiomyopathy-related RVOT-VAs in the presence of a small RVOT scar.

Response to Letter Regarding Article, “Growth Properties of Cardiac Stem Cells Are a Novel Biomarker of Patients’ Outcome After Coronary Bypass Surgery”

We appreciate the interest of Drs Li and Shen in our study,1 which emphasizes the critical role that the insulin-like growth factor-1 (IGF-1) and IGF-1 receptor system has in defining the growth properties of human cardiac stem cells (hCSCs). We shared their view that IGF-1 positively interferes with the consequences of diabetes mellitus and dyslipidemia, and possibly with other cardiovascular pathologies. Based on our interest in IGF-1, a transgenic mouse model with cardiomyocyte-restricted overexpression of IGF-1 was developed.2 With this strategy, an increase in the number of ventricular myocytes was obtained, resulting in a significantly lower systolic and diastolic stress at the cellular level, together with an enhanced ability of the myocardium to sustain increases in pressure or volume loads. Overexpression of IGF-1 prevents the manifestation of the diabetic myopathy and is associated with a …