Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p < 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p < 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p < 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p < 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p < 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated

Disturbi del ritmo sonno-veglia nella Distrofia Miotonica di tipo 1: macrostruttura e microstruttura del sonno

La Distrofia Miotonica di tipo 1 (DM1), malattia genetica a trasmissione autosomica dominante, è la più comune forma di distrofia muscolare a esordio in età adulta. Tra i numerosi sintomi che ne configurano il quadro clinico, troviamo l’eccessiva sonnolenza diurna (ESD) e la fatica, e frequente è la comorbidità con disturbi respiratori in sonno (DRS) e movimenti periodici degli arti inferiori (PLMS). Lo studio degli aspetti sonno-correlati in questa popolazione clinica ha finora privilegiato la caratterizzazione della sintomatologia e delle comorbidità, mentre le analisi di tipo quantitativo hanno valutato la macrostruttura, evidenziando un incremento del REM, con rilievo di addormentamenti in sonno REM (SOREM), a suggerire un possibile fenotipo simil-narcolettico. Nessuno studio, invece, ha valutato i parametri riguardanti la microstruttura del sonno secondo il modello del cyclic alternating pattern (CAP), un ritmo di instabilità endogeno, periodico e spontaneo, proprio del sonno NREM che, attraverso eventi transitori ed ordinati di attivazione elettroencefalografica ed autonomica, partecipa all’organizzazione dinamica del sonno e presenta importanti risvolti neurofisiologici e cognitivi. Scopo del nostro studio è stato valutare i parametri macrostrutturali e microstrutturali (secondo il modello del CAP) del sonno notturno in una popolazione di pazienti con DM1, nonché la presenza di comorbidità quali disturbi respiratori in sonno e movimenti periodici degli arti inferiori. Abbiamo inoltre studiato i correlati sintomatologici della patologia (fatica ed eccessiva sonnolenza diurna) attraverso questionari standardizzati e, per quanto riguarda la sonnolenza diurna, metodiche oggettive (test delle latenze multiple del sonno, MSLT). Abbiamo incluso otto pazienti con diagnosi di DM1 e dieci controlli sani, che sono stati sottoposti a polisonnografia notturna in laboratorio. Le registrazioni così ottenute sono state analizzate secondo i parametri standardizzati per la valutazione della macrostruttura e della microstruttura del sonno, della potenza della banda delta, così come degli eventi respiratori e muscolari. Tutti i soggetti arruolati nello studio sono stati inoltre sottoposti all’MSLT per la valutazione della latenza di sonno e della latenza del primo sonno REM (FRL). Per la valutazione soggettiva di sonnolenza e fatica sono state adottate rispettivamente la Epworth Sleepiness Scale (ESS) e la Fatigue Severity Scale (FSS). Da un punto di vista macrostrutturale, i pazienti presentavano un incremento della percentuale di sonno REM rispetto al tempo totale di sonno (TST) (26,4±9,4% vs 17,3±4,4%; p=0,034) e una corrispondente riduzione della durata e della percentuale di N2 (39,9±9,2% vs 56,9±4,5%; p<0,001). Inoltre, pur non raggiungendo la significatività statistica, i pazienti mostravano un aumento della percentuale di N3 e una riduzione del TST e della FRL, che in tre pazienti soddisfaceva i criteri per SOREM. L’analisi della potenza della banda delta applicata allo stadio N3 indica una minor efficienza della slow wave activity (SWA) in questo stadio di sonno (33,3±15,3 μV2 nei pazienti e 67,0±30,5 μV2 nei controlli, per la banda 0,5-4,0 Hz; p<0,001). Da un punto di vista microstrutturale, il sonno dei pazienti appariva più instabile, con un incremento del CAP rate rispetto ai controlli (52,6±5,4% vs 42,7±10,9%; p=0,043), senza ulteriori differenze statisticamente significative per gli altri parametri microstrutturali esaminati. Due pazienti presentavano un indice di apnea-ipopnea (AHI) patologico (11,6 e 11,0), indicativo di una sindrome delle apnee notturne di grado lieve. Due pazienti mostravano indici di movimenti periodici degli arti inferiori (PLMS Index) nettamente patologici (44,6 e 36,6). La latenza media di sonno all’MSLT è stata significativamente inferiore nei pazienti rispetto ai controlli (8,9±3,1 minuti vs 14,4±2,9 minuti; p=0,004). Quattro pazienti hanno riportato una latenza media inferiore a 8 minuti, indicativa di ESD. Due pazienti mostravano un SOREM in una sola prova, mentre altri tre pazienti hanno presentato un SOREM in due delle cinque prove dell’MSLT; nessuno dei controlli ha presentato SOREM. L’andamento della latenza media nelle diverse prove dell’MSLT rivela nei pazienti un nadir nella prima prova; ciò potrebbe essere correlato a una compromissione dei meccanismi implicati nella regolazione del processo circadiano. Per quanto riguarda le scale soggettive, due pazienti presentavano un punteggio di ESS superiore a 10; un paziente ha ottenuto alla FSS un punteggio superiore a 4. I risultati del nostro studio confermano quanto già riportato in letteratura circa la macrostruttura del sonno nei pazienti DM1, che presenta un pattern peculiare con incremento della pressione del sonno REM. L’incremento del sonno REM, il rilievo clinico di ESD e quello strumentale di SOREM configurano un fenotipo simil-narcolettico, seppur con una propria specificità legata alla tendenza all’incremento del sonno profondo e all’aumento dell’instabilità del sonno valutata attraverso l’analisi del CAP. In conclusione, i dati del nostro lavoro evidenziano un’alterazione dell’organizzazione del sonno notturno nei pazienti DM1 che riguarda il processo omeostatico S (riduzione della SWA, aumento del CAP rate, tendenza all’aumento di N3), il processo circadiano C (alterato andamento della latenza di sonno nelle diverse prove dell’MSLT) e anche il processo ultradiano (incrementata pressione del sonno REM con riduzione della sua latenza). I nostri dati sono in linea con le numerose evidenze che vogliono alla base delle diverse alterazioni del sonno nella DM1 (compresi l’aumento dell’instabilità e l’eccessiva sonnolenza diurna), un’alterazione di meccanismi a livello centrale, legata alla compromissione dei sistemi neurotrasmettitoriali, in particolare quelli relativi alla serotonina e all’orexina

Disruption of sleep-wake continuum in myotonic dystrophy type 1: Beyond conventional sleep staging

Sleep disruption and excessive daytime sleepiness are well recognised symptoms in myotonic dystrophy type 1 (DM1), where a central dysfunction of sleep-wake regulation may play a pivotal role. Few studies evaluated sleep macrostructure in DM1, but none investigated more refined sleep variables. Eight DM1 patients (6 male, aged 20-50 years) and 10 healthy controls (7 male, aged 22-67 years) underwent nocturnal polysomnography and multiple sleep latency test. Sleep stages and events were scored according to standard criteria; sleep microstructure was analyzed through cyclic alternating pattern. Relative and absolute delta powers were computed for whole non REM and each non REM period. DM1 patients showed increased REM sleep and decreased N2. N3, although not significantly, was increased. Three patients, but no controls, had sleep-onset REM period in nocturnal sleep. DM1 patients showed slower delta power dissipation across the night, and increased sleep instability (CAP rate). Multiple sleep latency tests showed shorter sleep latencies, five patients presenting at least one sleep-onset REM period and, when including also night sleep, two sleep-onset REM periods. Our data confirm a narcoleptic-like phenotype in DM1 with a prominent REM sleep dysregulation, that may account for daytime sleepiness, together with increased sleep instability and impaired delta power dissipation that seem peculiar of the disease

Time- and frequency-domain analysis of repolarization phase during recovery from exercise in healthy subjects

Background/aim: Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system and controlled breathing on different myocardial repolarization markers in healthy subjects. Method: Myocardial repolarization dispersion markers from short period (5-minutes) ECG analysis (time and frequency domain) have been obtained in 21 healthy volunteers during these conditions: free breathing (rest); controlled breathing (resp); the first 5-minutes of post-exercise recovery phases (exercisePeak); maximum sympathetic activation, and during the second five minutes of post-exercise recovery phases (exerciseRecovery), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp) and T peak - T end intervals (Te). Results: During the exercisePeak major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, Te standard deviations (QTeSD, QTpSD, TeSD), variability indexes (QTeVI, QTpVI), normalized variances (QTeVN, QTpVN, TeVN), the ratio between short term QTe, QTp, Te variability RR (STVQTe/RR, STVQTp/RR and STVTe/RR increased. During exerciserecovery QTpSD (p&lt;0.05), QTpVI (p&lt;0.05), QTeVN (p&lt;0.05), QTpVN (p&lt;0.001), TeVN (p&lt;0.05), STVQTe/RR (p&lt;0.05), STVQTp/RR (p&lt;0.001) and STVTe/RR (p&lt;0.001) were significantly higher in comparison with the rest. The slope between QTe (0.24±0.06) or QTp (0.17±0.06) and RR were significantly higher than Te (0.07±0.06, p&lt;0.001). Conclusion: Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects whereas they do not alter any spectral components

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure

Background/objectives: The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. Method: We used 5 minutes ECG recordings to assess the mean, standard deviation (SD) and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. Results: QTpSD (p&lt;0.01), TeSD (p&lt;0.01), QTpVN (p&lt;0.01) and TeVN (p&lt;0.01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: 0.015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%) and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p:0.041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: 0.010) and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p:0.012). Conclusion: In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162) This article is protected by copyright. All rights reserved. Keywords: Chronic heart failure; QT; QTVI; Tpeak-Tend; mortality; permanent atrial fibrillation; temporal dispersion of repolarization phase

Age, gender and drug therapy influences on Tpeak-tend interval and on electrical risk score

Background and objectives: Electrical risk score (ERS) has been proposed as easy, inexpensive test to stratify of sudden cardiac death (SCD) risk in subjects with normal left ventricular function. Potentially, aging, gender and drugs can influence ERS affecting two on six electrical markers, particularly, those based on the repolarization. Aim of this study was to establish aging, gender and drug therapy possible influences on ERS and mortality in elderly patients. Method: 237 consecutive, low SCD risk-outpatients with asymptomatic and treated cardiovascular risk factors were analyzed. Six simple ECG markers composed ERS: heart rate (N75 bpm); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS transition zone (≥V4), frontal QRS-T angle (N90°), long QTBazett; long T peak to T end interval (Tp-e). We obtained ERS in 237 outpatients, grouped according age (b40 ys, ≥40 to b60 ys and ≥60 ys), gender and drug therapy with or without possible influence on the repolarization phase. Results: Two-hundred-thirty-seven patients were grouped respectively in the following age classes: b40 years old; ≥40 to b60 years old and ≥60 years old. ERS (p b 0.05), QTBazett (p b 0.001), Tp-e (p b 0.001) were higher in older subjects independently from gender, drug therapy and cardiovascular comorbidity. After two years we reported a 7.3% of mortality in the older groups; age (deceased versus survivors: 80 ± 4 versus 73 ± 7 years, p b 0.05) and Tp-e (deceased versus survivors: 117 ± 15 versus 93 ± 21 ms, p b 0.05) were significantly lower in survivors,multivariable logistic regression analysis selected only the Tp-e as significant risk factor for totalmortality (odd ratio 1.06, 95% CI: 1.01–1.12, p b 0.05). Conclusion: Aging was associated to the ERS and repolarization phase derangement. Tp-e should be considered a marker of total mortality rather than SCD in the over sixty years old patients

Time‐ and frequency‐domain analysis of repolarization phase during recovery from exercise in healthy subjects

Background/aim: Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system and controlled breathing on different myocardial repolarization markers in healthy subjects. Method: Myocardial repolarization dispersion markers from short period (5-minutes) ECG analysis (time and frequency domain) have been obtained in 21 healthy volunteers during these conditions: free breathing (rest); controlled breathing (resp); the first 5-minutes of post-exercise recovery phases (exercisePeak); maximum sympathetic activation, and during the second five minutes of post-exercise recovery phases (exerciseRecovery), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp) and T peak - T end intervals (Te). Results: During the exercisePeak major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, Te standard deviations (QTeSD, QTpSD, TeSD), variability indexes (QTeVI, QTpVI), normalized variances (QTeVN, QTpVN, TeVN), the ratio between short term QTe, QTp, Te variability RR (STVQTe/RR, STVQTp/RR and STVTe/RR increased. During exerciserecovery QTpSD (p&lt;0.05), QTpVI (p&lt;0.05), QTeVN (p&lt;0.05), QTpVN (p&lt;0.001), TeVN (p&lt;0.05), STVQTe/RR (p&lt;0.05), STVQTp/RR (p&lt;0.001) and STVTe/RR (p&lt;0.001) were significantly higher in comparison with the rest. The slope between QTe (0.24±0.06) or QTp (0.17±0.06) and RR were significantly higher than Te (0.07±0.06, p&lt;0.001). Conclusion: Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects whereas they do not alter any spectral components

Short-period temporal dispersion repolarization markers predict 30-days mortality in decompensated heart failure

Background and Objectives: Electrocardiographic (ECG) markers of the temporal dispersion of the myocardial repolarization phase have been shown able to identify chronic heart failure (CHF) patients at high mortality risk. The present prospective single-center study sought to investigate in a well-characterized cohort of decompensated heart failure (HF) patients the ability of short-term myocardial temporal dispersion ECG variables in predicting the 30-day mortality, as well as their relationship with N-terminal Pro Brain Natriuretic Peptide (NT-proBNP) plasmatic values. Method:One hundred and thirteen subjects (male: 59, 67.8%) with decompensated CHF underwent 5 min of ECG recording, via a mobile phone. We obtained QT end (QTe), QT peak (QTp) and T peak to T end (Te) and calculated the mean, standard deviation (SD), and normalized index (VN). Results: Death occurred for 27 subjects (24%) within 30 days after admission. Most of the repolarization indexes (QTe mean (p &lt; 0.05), QTeSD (p &lt; 0.01), QTpSD (p &lt; 0.05), mean Te (p &lt; 0.05), TeSD (p &lt; 0.001) QTeVN (p &lt; 0.05) and TeVN (p &lt; 0.01)) were significantly higher in those CHF patients with the highest NT proBNP (&gt;75th percentile). In all the ECG data, only TeSD was significantly and positively related to the NT-proBNP levels (r: 0.471; p &lt; 0.001). In the receiver operating characteristic (ROC)analysis, the highest accuracy for 30-day mortality was found for QTeSD (area under curve, AUC: 0.705, p &lt; 0.01) and mean Te (AUC: 0.680, p &lt; 0.01), whereas for the NT-proBNP values higher thanthe 75th percentile, the highest accuracy was found for TeSD (AUC: 0.736, p &lt; 0.001) and QTeSD (AUC: 0.696, p &lt; 0.01). Conclusion: Both mean Te and TeSD could be considered as reliable markers of worsening HF and of 30-day mortality. Although larger and possibly interventional studies are needed to confirm our preliminary finding, these non-invasive and transmissible ECG parameters could be helpful in the remote monitoring of advanced HF patients and, possibly, in their clinical management. (ClinicalTrials.gov number, NCT04127162)