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) electrocardiogram (ECG) analysis (time and frequency domain) have been obtained in 21 healthy volunteers during the following conditions: free breathing (rest); controlled breathing (resp); the first 5 minutes of postexercise recovery phases (exercisePeak ), maximum sympathetic activation; and during the second 5 minutes of postexercise 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, and Te standard deviations (QTeSD , QTpSD , and TeSD ); variability indexes (QTeVI and QTpVI), normalized variances (QTeVN, QTpVN, and TeVN); and the ratio between short-term QTe, QTp, and Te variability RR (STVQTe/RR , STVQTp/RR, and STVTe/RR ) increased. During exerciseRecovery , QTpSD (P < .05), QTpVI (P < .05), QTeVN (P < .05), QTpVN (P < .001), TeVN (P < .05), STVQTe/RR (P < .05), STVQTp/RR (P < .001), and STVTe/RR (P < .001) were significantly higher in comparison to 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 < .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.

Hospital mortality in decompensated heart failure. A pilot study.

BACKGROUND/AIM: Heart failure is a leading cause of morbidity and mortality worldwide and it is a major cause of emergency department access for cardiovascular disease patients. Aim of this study was to identify the electrocardiographic (ECG) markers, based on short-term temporal repolarization dispersion, capable to individuate decompensated chronic heart failure (CHF) patients at high mortality risk. METHODS: We obtained the following variables from an ECG recording, monitored via mobile phone, during 5-minute recordings in decompensated CHF patients: RR, QT end (QTe), QT peak (QTp) and T peak to T end (Te) and we calculated mean, standard deviation (SD) and normalized index (N). RESULTS: In-hospital mortality occurred for 25 subjects on 101 studied (25%). Deceased patients showed higher QTeSD (p < 0.01), Te mean (p < 0.01), TeSD (p < 0.05), QTeVN (p < 0.05) than the surviving group. Logistic multivariable analysis evidenced that Te mean was a significant predictor of in-hospital mortality (odd ratio: 0.09, 95% confidence limit: 0.02-0.35, p: 0.001). At multiple regression analysis, TeSD was significantly and positively related only to the NT-pro BNP levels (r: 0.540; p < 0.001). The Te mean (AUC: 0.677 p < 0.01) and TeSD (AUC: 0.647, p: 0.05) showed significant sensitivity/specificity for the event. CONCLUSIONS: The Te mean and TeSD seem to be a promising noninvasive clinical marker able to identify patients with decompensated CHF at high risk of in-hospital mortality.

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 (>75 bpm); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS transition zone (≥V4), frontal QRS-T angle (>90°), long QTBazett; long T peak to T end interval (Tp-e). We obtained ERS in 237 outpatients, grouped according age (<40 ys, ≥40 to <60 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: <40 years old; ≥40 to <60 years old and ≥60 years old. ERS (p < 0.05), QTBazett (p < 0.001), Tp-e (p < 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 < 0.05) and Tp-e (deceased versus survivors: 117 ± 15 versus 93 ± 21 ms, p < 0.05) were significantly lower in survivors, multivariable logistic regression analysis selected only the Tp-e as significant risk factor for total mortality (odd ratio 1.06, 95% CI: 1.01-1.12, p < 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.

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 < 0.05), QTeSD (p < 0.01), QTpSD (p < 0.05), mean Te (p < 0.05), TeSD (p < 0.001) QTeVN (p < 0.05) and TeVN (p < 0.01)) were significantly higher in those CHF patients with the highest NT-proBNP (>75th percentile). In all the ECG data, only TeSD was significantly and positively related to the NT-proBNP levels (r: 0.471; p < 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 < 0.01) and mean Te (AUC: 0.680, p < 0.01), whereas for the NT-proBNP values higher than the 75th percentile, the highest accuracy was found for TeSD (AUC: 0.736, p < 0.001) and QTeSD (AUC: 0.696, p < 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).

Arrhythmic Risk in Elderly Patients Candidates to Transcatheter Aortic Valve Replacement: Predictive Role of Repolarization Temporal Dispersion.

BACKGROUND/AIM: 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). METHODS: In eighty-one elderly patients with AS we calculated several short-period RR- and QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). RESULTS: 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 (LFRRN U) (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). CONCLUSION: 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 reduction of the arrhythmic burden in this setting of patients is worthy to be investigated.

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.

Possible predictive role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients: preliminary data.

OBJECTIVES: To evaluate the predicative power of the electrical risk score (ERS), a noninvasive and inexpensive test obtained by means of a standard 12-lead electrocardiogram (ECG), in a cohort of elderly patients who had undergone transcatheter aortic valve replacement (TAVR). METHODS: Survivors and non-survivors after TAVR at 1-year follow-up were compared in respect to the pre-procedural ERS as well as a number of other clinical and instrumental variables. ERS is composed of seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS transition zone (≥ V4); frontal QRS-T angle (>90°); long QTBazett (>450 ms for men and >460 in women) or JTBazett (330 ms for men and >340 ms for women); and long Tpeak to Tend interval (Tp-e) (>89 ms). The trial was registered in ClinicalTrials.gov as NCT03145376. RESULTS: A total of 40 patients were evaluated. During the follow-up, the all-cause mortality rate was 25% (ten patients) with 15% of cardiovascular death (six patients). The ERS was the strongest predictor of all-cause (odds ratio 3.73, 95% CI: 1.44-9.66, P<0.05) or cardiovascular (odds ratio 3.95, 95% CI: 1.09-14.27, P<0.05) mortality. Receiver operating characteristic curves showed that ERS had the widest significant sensitivity-specificity area under the curve (AUC) predicting all-cause (AUC: 0.855, P<0.05) or cardiovascular mortality (AUC: 0.908, P<0.05). CONCLUSION: ERS seems to be a useful noninvasive tool able to stratify the risk of mortality in 1-year follow-up of TAVR patients. These findings, however, require larger trials to be confirmed.

Transcranial direct current stimulation enhances soothing positive affect and vagal tone.

Transcranial Direct Current Stimulation (tDCS) is a promising tool for the treatment of depression and the dorsolateral prefrontal cortex (dlPFC) is often targeted when exploring tDCS effects on mood. However, the basic effects of tDCS on momentary emotions are inconsistent. We tested whether a single-session of anodal tDCS over the left temporal lobe (T3), topographically closer to the insular cortex than dlPFC, had effects on both vagally-mediated heart rate variability (HRV) and momentary affect in healthy participants. Thirty-four subjects underwent both sham and active tDCS in a counterbalanced random order. ECG was continuously recorded to derive both time and frequency domain HRV indexes. Before and after the tDCS protocol, participants completed momentary affect assessments. Results showed that HRV and soothing positive affectivity were both enhanced after a single-session of tDCS over T3, while negative and activating positive affect were not modulated by the stimulation. After controlling for sex, age, and levels of anxiety and depression a significant association emerged between increases in soothing positive affect and concomitant increases in vagally-mediated HRV. Deficits in soothing positive emotions have consistently been associated with psychopathology and psychotherapeutic approaches aimed to develop this type of emotionality have shown to improve psychological well-being. Thus, present exploratory results may impact future research investigating potential moderators (site of stimulation) and mediators (specificity for a determined type of momentary affect) of the effects of tDCS on psychopathological conditions such as depression.

Time- and frequency-domain analysis of beat to beat P-wave duration, PR interval and RR interval can predict asystole as form of syncope during head-up tilt.

To seek possible differences in short-period temporal RR interval, P-wave and PR interval dispersion and spectral coherence in patients with a head-up tilt test positive for vasovagal syncope with or without prolonged asystole, severe symptoms and at high risk of trauma. We retrospectively reviewed 5 min ECG and blood pressure recordings obtained at baseline, at rest and during head-up tilt in 40 patients diagnosed as having recurrent vasovagal syncope confirmed at a head-up tilt test. We analysed autoregressive spectral power for all the ECG-derived variables, focusing on temporal P-wave and PR interval dispersion indexes as well as their spectral coherence calculated on the same 5 min recordings at rest and during tilt. ECG recordings obtained during tilt before syncope showed significantly lower P → PR spectral coherence and higher RR standard deviations in patients with tilt-induced asystole than in those without (0.567 ± 0.097 versus 0.670 ± 0.127, p: 0.010 and 84 ± 36 versus 46 ± 22 ms2, p < 0.0001). Differences in the RR standard deviations persisted also on the last hundred beats (-100) (113 ± 54 versus 34 ± 17 ms2, p < 0.0001). Multiple regression analysis identified a significantly negative association between the maximum RR intervals and P → PR coherence at rest (ß: -0.3, p < 0.05) and positive association with RR-100 standard deviation during tilt-induced syncope (ß: 0.621, p < 0.001). P → PR spectral coherence could be used to assess the risk of prolonged asystole in patients with tilt-induced vasovagal syncope as well as as a possible surrogate for tilt-testing during these patients' follow-up.

Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years.

BACKGROUND: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. OBJECTIVE: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. SUBJECTS AND METHODS: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. RESULTS: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05). CONCLUSION: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity.

Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines.

INTRODUCTION: Migraine is a multifactorial neurovascular disorder characterized by recurrent episodes of disabling pain attacks, accompanied with gastrointestinal, neurological systems dysfunction. The pharmacologic treatment of migraine is classically divided in the management of the acute attack and preventive strategies. Acute treatments consist of triptan, ergot, opioid, antiemetic and NSAIDs. AREAS COVERED: This article discusses pharmacodynamics and pharmacokinetics of zolmitriptan . The data were obtained by searching the following keywords in MEDLINE: zolmitriptan, pharmacokinetics, pharmacodynamics, triptans, migraine, menstrual-related migraine, cluster headache, relatively to the period 1989 - 2012. EXPERT OPINION: Zolmitriptan has been considered effective treatment in the acute phase of migraine, menstrual-related migraine and cluster headache attacks. Pharmacokinetic parameters may vary as a consequence of gender differences, inter- and intra-subjects variability and delivery system. Zolmitriptan was developed with the aim of obtaining a lipophilic compound in order to be more rapidly absorbed and centrally active. Pharmacologically, pharmacokinetic parameters are responsible for its wide efficacy and the limited adverse effect profile.