Oscillatory behavior of P wave duration and PR interval in experimental congestive heart failure: a preliminary study.

OBJECTIVE: The relationship between the autonomic nervous system (ANS) modulation of the sinus node and heart rate variability has been extensively investigated. The current study sought to evaluate, in an animal experimental model of pacing-induced tachycardia congestive heart failure (CHF), a possible ANS influence on the P wave duration and PR interval oscillations. APPROACH: Short-term (5 min) time and frequency domain analysis has been obtained in six dogs for the following electrocardiographic intervals: P wave duration (P), from the onset to peak of P wave (P p), from the onset of P wave to the q onset (PR) and from the end of P wave to the onset of q wave (P e R). Direct vagal nerve activity (VNA), stellate ganglion nerve activity (SGNA) and electrocardiogram (ECG) intervals have been evaluated contextually by implantation of three bipolar recording leads. MAIN RESULTS: At the baseline, multiple regression analysis pointed out that VNA was strongly positively associated with the standard deviation of PP and P e R intervals (r 2:0.997, p < 0.05). The same variable was also positively associated with high-frequency (HF) of P expressed in normalized units, of P p, and of P e R (b: 0.001) (r 2: 0.993; p < 0.05). During CHF, most of the time and frequency domain variability significantly decreased from 20% to 50% in comparison to the baseline values (p < 0.05) and SGNA correlated inversely with the low frequency (LF) obtained from P e R (p < 0.05) and PR (p < 0.05) (r 2:0.899, p < 0.05). LF components, expressed in absolute and normalized power, obtained from all studied intervals, were reduced significantly during CHF. Any difference between the RR and PP spectral components was observed. SIGNIFICANCE: The data showed a significant relationship between ANS and atrial ECG variables, independent of the cycle duration. In particular, the oscillations were vagal mediated at the baseline, while sympathetic mediated during CHF. Whereas P wave variability might have a clinical utility in CHF management, it needs to be addressed in specific studies.

P wave analysis and left ventricular systolic function in chronic heart failure. Possible insights form the P wave - PP interval spectral coherence.

BACKGROUND: Chronic increase in left ventricular filling pressure represents one of the most important mechanism underlying the structural, as well as the electrical, atrial chamber remodeling leading to atrial fibrillation. The present pilot pathophysiological study sought to investigate possible relationship between short-period cross-spectral coherence of P-Q, R-R and P-P intervals and echocardiographic indices of left ventricular and atrial function. METHODS: Electrocardiographic single lead short-term cross-spectral analysis on P-Q and P-P intervals was performed in 31 patients with chronic heart failure (CHF). Twenty age and therapy matched hypertensive patients acted as control group. The interval between the beginning of P wave and its peak (Ppeak) was also analyzed. RESULTS: Patients with CHF showed a significant lower PQ → PP and Ppeak → PP coherence (P<0.001) than the counterpart. At multivariate analysis only Ppeak → PP was independently associated to LVEF (r2:0.312; b:60; ß:0.559; P<0.0001) and atrial volume (r2:-0.160; b:-0.15; ß:-0.400, P<0.05). CONCLUSIONS: Ppeak → PP coherence might be a simple marker of left ventricular and atrial function. Whether this index could be a useful noninvasive marker of increased left ventricular filling pressure and, possibly, of atrial fibrillation risk or not, it needs to be tested in larger prospective studies.

Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH.

BACKGROUND: Conventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%. RESULTS: In a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb). FISH analysis could be performed on six cases and showed that rearrangements were translocation derivatives, indistinguishable from a normal karyotype as they involved a similar band pattern and size. Five were inherited from a parent with a balanced translocation, whereas two were apparently de novo. Genes spanning the rearrangements could be associated with some phenotypic features in three cases (case 3: DOCK8; case 4: GATA3, AKR1C4; case 6: AS/PWS deletion, CHRNA7), and in two, likely disease genes were present (case 5: NR2F2, TP63, IGF1R; case 7: CDON). Three of our cases were prenatal diagnoses with an apparently normal karyotype. CONCLUSIONS: Large complex rearrangements of up to 18 Mb, involving chromosomal regions with similar size and band appearance may be overlooked by conventional karyotyping. Array-CGH allows a precise chromosomal diagnosis and recurrence risk definition, further confirming this analysis as a first tier approach to clarify molecular bases of ID/DD and/or MCA. In prenatal tests, array-CGH is confirmed as an important tool to avoid false negative results due to karyotype intrinsic limit of detection.

Myocardial repolarization dispersion and autonomic nerve activity in a canine experimental acute myocardial infarction model.

BACKGROUND: Evidence from a canine experimental acute myocardial infarction (MI) model shows that until the seventh week after MI, the relationship between stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) progressively increases. OBJECTIVE: The purpose of this study was to evaluate how autonomic nervous system activity influences temporal myocardial repolarization dispersion at this period. METHODS: We analyzed autonomic nerve activity as well as QT and RR variability from recordings previously obtained in nine dogs. From a total of 48 short-term ECG segments, 24 recorded before and 24 recorded 7 weeks after experimentally-induced MI, we obtained three indices of temporal myocardial repolarization dispersion: QTe (from Q-wave to T-wave end), QTp (from Q-wave to T-wave peak), and Te (from T-wave peak to T-wave end) variability index (QTeVI, QTpVI, TeVI). We also performed heart rate variability power spectral analysis on the same segments. RESULTS: After MI, all the QT variables increased QTeVI (median [interquartile range]) (from -1.76[0.82] to -1.32[0.68]), QTeVI (from -1.90[1.01] to -1.45[0.78]), and TeVI (from -0.72[0.67] to -0.22[1.00]), whereas all RR spectral indices decreased (P <.001 for all). Distinct circadian rhythms in QTeVI (P <.05,) QTpVI (P <.001) and TeVI (P <.05) appeared after MI with circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI acrophase coincided with another SGNA/VNA peak. After MI, regression analysis detected a positive relationship between SGNA/VNA and TeVI (R(2): 0.077; ß: 0.278; p< 0.001). CONCLUSION: Temporal myocardial repolarization dispersion shows a circadian variation after MI reaching its peak at a time when sympathetic is highest and vagal activity lowest.

Influence of aging and chronic heart failure on temporal dispersion of myocardial repolarization.

BACKGROUND AND PURPOSE: QT and T(peak)-T(end) (Te) intervals are associated with sudden cardiac death in patients with chronic heart failure (CHF). We studied age-dependent influence on short-term temporal dispersion of these two variables in patients with postischemic CHF. METHOD: We grouped 75 CHF and 53 healthy control subjects into three age subsets: ≤ 50 years, >50 years and ≤ 65 years, and >65 years. We then calculated the following indices: QT and Te variability index (QTVI and TeVI), the ratio between the short-term variability (STV) of QT or Te, and the STV of resting rate (RR) (QT/RR STV and Te/RR STV). RESULTS: In all different age subgroups, patients with CHF showed a higher level of QTVI than age-matched control subjects (≤ 50 years: P < 0.0001; >50 years and ≤ 65 years: P < 0.05; >65 years: P < 0.05). Patients with CHF < 50 years old also had all repolarization variability indices higher than normal age-matched controls (TeVI, P < 0.05; QT/RR STV, P < 0.05; Te/RR STV, P < 0.05), whereas we did not find any difference between the two older classes of subjects. Both QTVI (r²: 0.178, P < 0.05) and TeVI (r²: 0.433, P < 0.001) were positively related to age in normal subjects, even if the first correlation was weaker than the second one. CONCLUSION: Our data showed that QTVI could be used in all ages to evaluate repolarization temporal liability, whereas the other indices are deeply influenced by age. Probably, the age-dependent increase in QTVI was more influenced by a reduction of RR variability reported in older normal subjects.