Cardiac Intervals Research Articles

The Impact of Beta-blockade on Right Ventricular Function in Mitral Regurgitation

Although mitral regurgitation (MR) results in left ventricular (LV) volume overload, right ventricular (RV) function may also be impaired. We investigated the influence of short-term beta-blockade on RV function in patients with moderate-severe MR. Twenty-six patients were randomised in a cross-over design to receive two weeks of beta-blockade or placebo. Echocardiography was performed at baseline and at the end of the treatment periods. Measurements included: RV ejection fraction (RVEF) tricuspid annular motion and Tei index. No differences in mean RVEF (64.0 ± 6.0 v 67.0 ± 8.0%, p=0.3), tricuspid annular motion (13.5 ± 3.0 v 14.7 ± 2.9 cm/s, p=0.5), or median Tei index (0.61 (0.54, 0.88) v 0.59 (0.54, 0.74), p=0.8) were observed between placebo and metoprolol, despite significantly longer cardiac time intervals. Tei index under both conditions was significantly reduced. Short-term treatment with a beta-blocker did not influence RV function in these patients. Interestingly, the RV Tei index was high suggesting significant RV dysfunction despite normal RVEF.

Automated Estimation of Fetal Cardiac Timing Events From Doppler Ultrasound Signal Using Hybrid Models

In this paper, a new noninvasive method is proposed for automated estimation of fetal cardiac intervals from Doppler Ultrasound (DUS) signal. This method is based on a novel combination of empirical mode decomposition (EMD) and hybrid support vector machines-hidden Markov models (SVM/HMM). EMD was used for feature extraction by decomposing the DUS signal into different components (IMFs), one of which is linked to the cardiac valve motions, i.e. opening (o) and closing (c) of the Aortic (A) and Mitral (M) valves. The noninvasive fetal electrocardiogram (fECG) was used as a reference for the segmentation of the IMF into cardiac cycles. The hybrid SVM/HMM was then applied to identify the cardiac events, based on the amplitude and timing of the IMF peaks as well as the sequence of the events. The estimated timings were verified using pulsed doppler images. Results show that this automated method can continuously evaluate beat-to-beat valve motion timings and identify more than 91% of total events which is higher than previous methods. Moreover, the changes of the cardiac intervals were analyzed for three fetal age groups: 16-29, 30-35, and 36-41 weeks. The time intervals from Q-wave of fECG to Ac (Systolic Time Interval, STI), Ac to Mo (Isovolumic Relaxation Time, IRT), Q-wave to Ao (Preejection Period, PEP) and Ao to Ac (Ventricular Ejection Time, VET) were found to change significantly ( ) across these age groups. In particular, STI, IRT, and PEP of the fetuses with 36-41 week were significantly ( ) different from other age groups. These findings can be used as sensitive markers for evaluating the fetal cardiac performance.

Fetal cardiac tissue doppler: Effect of the doppler angle on time intervals

Material and methods: Pulsed Tissue Doppler measurements were performed in the right subvalvular ventricular myocardium and measured cardiac time intervals were used to calculate TD-Tei Index. We retrospectively examined 215 fetal cardiac tissue doppler measurements with regard to the doppler insonation angle using the intraventricular septum as reference. In 196 cases (91%) we were able to measure the angle of insonation.

A study about the clinical significance of cardiac QTc interval for predicting the mortality and prognostic of acute organophosphate poisoning

A study about the clinical significance of cardiac QTc interval for predicting the mortality and prognostic of acute organophosphate poisoning

Development and application of an automated extraction algorithm for fetal magnetocardiography – normal data and arrhythmia detection

Current standard methods of monitoring fetal heart function are mainly based on echocardiography, which provides indirect information (through mechanical assessment) of the fetal heart rhythm. Fetal magnetocardiography (fMCG) allows a reliable quantification of the temporal structure of fetal heart signals. However, its application in clinical studies is difficult because extracting the fetal heart signal for most current applications requires user intervention. To overcome this limitation, we developed a completely automated extraction algorithm. The fMCG recordings were acquired using a 156-channel biomagnetic system. To perform an automated analysis, a combination of orthogonal projection and independent component analysis was used. fMCG recordings from 69 healthy uncomplicated singleton pregnancies with normally developing fetuses were included in the study. The normal values achieved by the automated algorithm were comparable to previously published data. The majority of the cardiac time intervals were positively correlated with gestational age (GA). The ST segment, T wave and QT interval did not show any correlation. The automated detection of fetal heart signals was possible beginning at a GA of 19 weeks. This automated analysis of fMCG recordings might be an objective and easily applicable approach for clinicians to analyze fetal heart signals.

Analysis of loci from genome-wide association studies of many complex traits for association with late-onset Alzheimer's disease (LOAD) identifies potentially pleiotropic variants

While the majority of genome-wide association studies (GWAS) have focused on agnostic or “hypothesis-free” testing of associations with genomic variants, few studies have focused on variants with prior genome-wide associations to major complex diseases and traits to identify potential pleiotropic effects and common pathologic mechanisms between different diseases. As part of custom genotyping in the replication phase of a major LOAD GWAS meta-analysis, we genotyped and analyzed 1,099 autosomal SNPs from a catalog of GWAS associations in 8,042 cases and 9,387 controls in order to identify potentially pleiotropic effects of these variants on LOAD risk. We selected GWAS hits from the NHGRI GWAS Catalog (downloaded 07/01/11) for paneling on the Illumina iSelect custom microarray, excluding those in known CNVs or non-autosomal (n=97), associations of P>5.0×10 -8 (n=2,547), previous association with AD (n=21), or identification in a non-Caucasian sample (n=850), leaving 1,099 variants. After genotyping, 974 GWAS SNPs and 17,429 Caucasian subjects from the USA, Canada, and 9 countries in Europe passed QC. We performed logistic regression on LOAD risk modeling genetic effects additively with covariate adjustment for population substructure, sex, and age. Analyses were stratified by country of origin, and resulting country-specific associations were meta-analyzed. Nine GWAS SNPs demonstrated statistically significant associations after Bonferroni correction (P<5×10 -5) and limited evidence of heterogeneity (P>0.05). These variants were associated with chronic kidney disease (P =1.65×10 -7), cardiac QT interval (P =2.85×10 -6), HIV-1 non-progression (P =5.99×10 -6), rheumatoid arthritis (P =3.40×10 -5), glycated hemoglobin levels (P =3.53×10 -5), and plasma eosinophil count (P =4.20×10 -5). Three variants in the MHC region associated with LOAD also had previous associations with chronic lymphocytic leukemia (P =2.75×10 -5), HIV-1 non-progression (P =3.07×10 -5), and ankylosing spondylitis (P =3.21×10 -5). Testing association of 974 SNPs with LOAD identified potential pleiotropic effects of at least nine SNPs, including variants previously associated with heart disease and multiple autoimmune diseases. While some of these conditions share some common pathologic characteristics with LOAD, further analyses of these SNPs in other studies is necessary to replicate and confirm these potentially pleiotropic effects.

Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study

Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers. In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI). Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations. Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.

Predicting Drug‐Induced QT Prolongation and Torsades de Pointes: A Review of Preclinical Endpoint Measures

Compound-induced prolongation of the cardiac QT interval is a major concern in drug development and this unit discusses approaches that can predict QT effects prior to undertaking clinical trials. The majority of compounds that prolong the QT interval block the cardiac rapid delayed rectifier potassium current, IKr (hERG). Described in this overview are different ways to measure hERG, from recent advances in automated electrophysiology to the quantification of channel protein trafficking and binding. The contribution of other cardiac ion channels to hERG data interpretation is also discussed. In addition, endpoint measures of the integrated activity of cardiac ion channels at the single-cell, tissue, and whole-animal level, including for example the well-established action potential to the more recent beat-to-beat variability, transmural dispersion of repolarization, and field potential duration, are described in the context of their ability to predict QT prolongation and torsadogenicity in humans.

Quantifying heart rate dynamics using different approaches of symbolic dynamics

The analysis of symbolic dynamics applied to physiological time series is able to retrieve information about dynamical properties of the underlying system that cannot be gained with standard methods like e.g. spectral analysis. Different approaches for the transformation of the original time series to the symbolic time series have been proposed. Yet the differences between the approaches are unknown. In this study three different transformation methods are investigated: (1) symbolization according to the deviation from the average time series, (2) symbolization according to several equidistant levels between the minimum and maximum of the time series, (3) binary symbolization of the first derivative of the time series. Furthermore, permutation entropy was used to quantify the symbolic series. Each method was applied to the cardiac interbeat interval series RR i and its difference ΔRR I of 17 healthy subjects obtained during head-up tilt testing. The symbolic dynamics of each method is analyzed by means of the occurrence of short sequences (“words”) of length 3. The occurrence of words is grouped according to words without variations of the symbols (0V%), words with one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%). Linear regression analysis showed that for method 1 0V%, 1V%, 2LV% and 2UV% changed with increasing tilt angle. For method 2 0V%, 2LV% and 2UV% changed with increasing tilt angle and method 3 showed changes for 0V% and 1V%. Furthermore, also the permutation entropy decreased with increasing tilt angle. In conclusion, all methods are capable of reflecting changes of the cardiac autonomic nervous system during head-up tilt. All methods show that even the analysis of very short symbolic sequences is capable of tracking changes of the cardiac autonomic regulation during head-up tilt testing.

Cardiorespiratory coupling of sympathetic outflow in humans: a comparison of respiratory and cardiac modulation of sympathetic nerve activity to skin and muscle

What is the central question of this study?Muscle sympathetic nerve activity (MSNA) is well known to be modulated by the arterial baroreceptors and respiration, but what are the magnitudes of cardiac and respiratory modulation of skin sympathetic nerve activity (SSNA), which primarily subserves thermoregulation?What is the main finding and what is its importance?Using direct microelectrode recordings of MSNA and SSNA in awake humans, we show that the magnitude of respiratory modulation of SSNA is identical to that of MSNA, the primary difference between the two sources of sympathetic outflow being the greater cardiac modulation of MSNA. This emphasises the role of the baroreceptors in entraining sympathetic outflow to muscle. It is well known that microelectrode recordings of skin sympathetic nerve activity (SSNA) in awake human subjects reveal spontaneous bursts of activity with no overt modulation by changes in blood pressure or respiration, in contrast to the clear cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA). However, cross-correlation analysis has revealed that, like individual muscle vasoconstrictor neurones, the firing of individual cutaneous vasoconstrictor neurones is temporally coupled to both the cardiac and respiratory rhythms during cold-induced cutaneous vasoconstriction, and the same is true of single sudomotor neurones during heat-induced sweating. Here, we used cross-correlation analysis to determine whether SSNA exhibits cardiac and respiratory modulation in thermoneutral conditions and to compare respiratory and cardiac modulation of SSNA with that of MSNA. Oligounitary recordings of spontaneous SSNA (n = 20) and MSNA (n = 18) were obtained during quiet, unrestrained breathing. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Respiratory and cardiac modulation of SSNA and MSNA were quantified by fitting polynomial equations to the cross-correlation histograms constructed between the sympathetic spikes and respiration or ECG. The amplitude of the respiratory modulation (52.5 ± 3.4%) of SSNA was not significantly different from the amplitude of the cardiac modulation (46.6 ± 3.2%). Both were comparable to the respiratory modulation of MSNA (47.7 ± 4.2%), while cardiac modulation of MSNA was significantly higher (89.8 ± 1.5%). We conclude that SSNA and MSNA share similar levels of respiratory modulation, the primary difference between the two sources of sympathetic outflow being the marked cardiac modulation of MSNA provided by the baroreceptors.

ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel

Many studies have provided convincing evidence for hERG as an important diagnostic and prognostic factor in human cancers, as well as a useful target for antineoplastic therapy. Our previous study also revealed that knockdown of herg gene expression by shRNA interference inhibited the growth of neuroblastoma cells in vitro and in vivo. In the experiment, a novel 4-amino piperidine analog, ZC88, was examined for its effect on hERG potassium channels and its antitumor potency was observed in vitro and in vivo. The results showed that ZC88 could block hERG1 and hERG1b channels expressed in Xenopus oocytes in a concentration-dependent manner. ZC88 displayed significant antiproliferative activity in several tumor cell lines and the tumor cells with higher expression of hERG presented higher sensitivity to ZC88. The mitotic progression of tumor cells was markedly suppressed in the presence of ZC88 through arresting cells in G0/G1 phase. ZC88 significantly inhibited the tumor growth in nude mice at a dosage with slight influence on the cardiac QT interval. The antitumor effect of ZC88 was correlated at least partly with its blockage of hERG channels, which implicated a positive role of hERG potassium channel in tumor cell proliferation.

Cardiac vectors in the healthy human fetus: developmental changes assessed by magnetocardiography and realistic approximations of the volume conductor

This study sought to characterize the developmental changes of three measures used to describe the morphology of the fetal cardiac vector: QRS peak-amplitude, QRS duration and QRS time-amplitude integral. To achieve this objective, we rely on a recently developed methodology for fetal cardiac vector estimation, using multichannel fetal magnetocardiographic (fMCG) recordings and realistic approximations of the volume conductors obtained from free-hand ultrasound imaging. fMCG recordings and 3D ultrasound images were obtained from 23 healthy, uncomplicated pregnancies for a total of 77 recordings performed at gestational ages between 22 and 37 weeks. We report the developmental changes of the cardiac vector parameters with respect to gestational age and estimated fetal weight, as well as their dependence on the estimated ventricular mass derived from cardiac dimensions measured with M-mode ultrasound. The normative values can be used along with the cardiac time intervals reported by previous fMCG studies to assist future clinical studies investigating conditions that affect fetal cardiac function.

Mechanisms of causal interaction between short-term RR interval and systolic arterial pressure oscillations during orthostatic challenge

The transition from the supine to the upright position requires a reorganization of the mechanisms of cardiovascular control that, if not properly accomplished, may lead to neurally mediated syncope. We investigated how the patterns of causality between systolic arterial pressure (SAP) and cardiac RR interval were modified by prolonged head-up tilt using a novel nonlinear approach based on corrected conditional entropy (CCE) compared with the standard approach exploiting the cross-correlation function (CCF). Measures of coupling strength and delay of the causal interactions from SAP to RR and from RR to SAP were obtained in 10 patients with recurrent, neurally mediated syncope (RNMS) and 10 healthy control (CO) subjects in the resting supine position (su) and after head-up tilting during early (et; ~2 min) and late (lt; ~15 min or before presyncope) epochs of upright posture. Main results were that 1) the coupling strength from SAP to RR increased significantly from su to et in both groups; by contrast, upon lt, the coupling strength was kept high in CO subjects and dropped to low values in RNMS patients; 2) in RNMS patients, the delay from SAP to RR was higher than in healthy controls and increased moving from et to lt. Although these trends were evident using the CCE approach, statistical significance was not attained using the CCF approach. These results indicate the necessity of dissecting causality between RR and SAP to properly assess directional mechanisms from the closed-loop cardiovascular regulation and suggest a weakened and slowed baroreflex as a major mechanism involved in the cardiovascular impairment associated to neurally mediated syncope.

PP078. The influence of maternal position on gestational hemodynamics

Cardiovascular profiling is useful for gestational hemodynamic studies. Conflicting results of cardiac output evolution from third trimester pregnancy to term are frequently reported. To stress the effect of maternal position in the assessment of maternal cardiac and arterial parameters during normal pregnancy. Impedance cardiography measurements were executed during 16 normal pregnancies using a standard protocol with known reproducibility. Gestational evolution of stroke volume, cardiac output, cardiac cycle time intervals, aortic flow parameters and total peripheral vascular resistance was measured in supine, standing and sitting positions. SAS procedure MIXED for linear mixed models was used for each parameter separately. Evolution of stroke volume and cardiac output in supine position differed from standing (p<0.01) and sitting positions (p<0.05). Next to this, pre-ejection period, left ventricular ejection time index, systolic time ratio and total peripheral vascular resistance also showed a different evolution between supine and standing positions (p<0.05); no differences were observed between standing and sitting positions (p⩾0.19). Next to the frequently reported cardiac output, gestational evolutions of other pre-load dependent parameters are influenced by maternal position. This study shows the importance of a standardized protocol for the measurement of cardiovascular parameters in pregnancy.

Prognostic Value of Cardiac Time Intervals by Tissue Doppler Imaging M-Mode in Patients With Acute ST-Segment–Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

Color tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to estimate all cardiac time intervals from 1 cardiac cycle and thereby obtain the myocardial performance index (MPI). However, the prognostic value of the cardiac time intervals and the MPI assessed by color tissue Doppler imaging M-mode through the mitral leaflet in patients with ST-segment-elevation myocardial infarction (MI) is unknown. In total, 391 patients were admitted with an ST-segment-elevation MI, treated with primary percutaneous coronary intervention, and examined by echocardiography a median of 2 days after the ST-segment-elevation MI. Outcome was assessed according to death (n=33), hospitalization with heart failure (n=53), or new MI (n=25). Follow-up time was a median of 25 months. The population was stratified according to tertiles of the MPI. The risk of new MI, being admitted with congestive heart failure or death, increased with increasing tertile of MPI, being ≈3 times as high for the third tertile compared with the first tertile (hazard ratio, 2.8; 95% confidence interval, 1.7-4.7; P<0.001). MPI provided independent prognostic information in a multivariable Cox regression model adjusted for age, sex, previous MI, peak troponin, and systolic and diastolic echocardiographic parameters, with a hazard ratio of 1.24 (P=0.005) for the combined end point per each 0.1 increase in MPI. MPI assessed by tissue Doppler imaging M-mode is a simple and reproducible measure that provides independent prognostic information, regardless of rhythm, incremental to conventional and novel echocardiographic parameters of systolic and diastolic function in patients with ST-segment-elevation MI treated with primary percutaneous coronary intervention.

Prescription of drugs with potential adverse effects on cardiac conduction in Parkinson's disease

BackgroundEpidemiological studies report an association of ventricular arrhythmias with medication through prolongation of the cardiac QT interval. This has implications in the management of Parkinson's disease, as commonly prescribed drugs for non-motor symptoms and comorbidities have QT prolonging potential. ObjectivesTo review prescribed medication in Parkinson's disease patients, in particular the use of drugs that may prolong the cardiac QT interval, in relation to other risk factors for QT prolongation. MethodsMedication prescription and doses, presence of underlying cardiac disease, patient age, and sex were recorded in a cross-sectional sample of 360 current PD patients attending two district and one regional specialist hospital-based movement disorder clinics. ResultsWe sampled 360 consecutive patients with PD, median age 66.5 years (interquartile range 58.5–74.8) and median disease duration 4.2 years (interquartile range 1.2–8.0 years). 125 (34.7%) were taking one or more drugs with definite potential to prolong QT, including domperidone in 91 (25.2%), citalopram or escitalopram in 47 (13.1%), and concurrent antibiotics in 5 (1.3%). Cofactors increasing the risk for QT interval prolongation were: age over 60 years 71.7%, female sex 46.9%, and presence of cardiac disease 19.2%. In patients with combined risk factors, the rate of prescription of at least one definite QT prolonging drug was between 34.5 and 42.1%. ConclusionsCombination therapy and comorbidity relevant to cardiac QT prolongation are common in patients with Parkinson's disease. Strategies to reduce the proportion of patients at risk from iatrogenic adverse cardiac events are warranted.

The effect of routine magnesium supplementation on fetal cardiac time intervals: a fetal magnetocardiographic study

ObjectivesMagnesium deficiency in pregnancy is frequent, and in consequence magnesium supplementation is widely used. As magnesium crosses the placental barrier and since the fetal kidney does not excrete magnesium as efficiently as the mature kidney, effects on fetal cardiac time intervals are probable, but still unknown. Study designSixty pregnant women were included in an observational study: 31 patients received oral routine magnesium supplementation. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate electrophysiological rhythm patterns with high temporal resolution. fMCG tracings were analyzed according to a predefined procedure for fetal cardiac time interval (CTI)-detection. fCTI findings (P-wave, PQ-segment, PR-interval, QRS complex, ST segment, T-wave and QTc interval) were registered. ResultsSignificant widening of the QRS-complex (p=0.004) was demonstrated in fetuses whose mothers received magnesium supplementation (240mg/day) relative to the control group. ConclusionMagnesium exposed fetuses demonstrated a prolonged ventricular arousal, but healthy neonatal outcome was found in all exposed fetuses. Although fMCG is a preclinical method and limited in its availability, the procedure could help to monitor fetuses.

Relationship between changes in pulmonary kinetics and autonomic regulation of blood flow

Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.

Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats

The prolonged seizures of status epilepticus produce chronic arrhythmogenic changes in cardiac function. This study was designed to determine if repeated, self-limiting seizures administered to kindled rats induce similar cardiac dysfunction. Multiple seizures administered to rats following hippocampal kindling resulted in cardiac QT interval prolongation and increased susceptibility to experimental arrhythmias. These data suggest that multiple, self-limiting seizures of intractable epilepsy may have cardiac effects that can contribute to sudden unexpected death in epilepsy (SUDEP).

Influence of Serotonin Transporter Gene Polymorphism (5-HTTLPR Polymorphism) on the Relation between Brain 5-HT Transporter Binding and Heart Rate Corrected Cardiac Repolarization Interval

ObjectiveSerotonin transporter gene polymorphism (5-HTTLPR polymorphism) predicts the degree of structural and functional connectivity in the brain, and less consistently the degree of vulnerability for anxiety and depressive disorders. It is less known how 5-HTTLPR polymorphism influences on the coupling between brain and neuronal cardiovascular control. The present study demonstrates the impact of 5-HTTLPR polymorphism on the relations between heart rate (HR) corrected cardiac repolarization interval (QTc interval) and the brain 5-HTT binding.Material and MethodsThirty healthy young adults (fifteen monozygotic twin pairs) (mean age 26±1.3 years, 16 females) were imagined with single-photon emission computed tomography (SPECT) using iodine-123 labeled 2β-carbomethoxy-3β-(4-iodophenyl) nortropane (nor-β-CIT). Continuous ECG recording was obtained from each participant at supine rest. Signal averaged QTc interval on continuous ECG was calculated and compared with the brain imaging results.ResultsIn the two groups [l homozygotes (n = 16, 10 females), s carriers (n = 14, 8 female)] HR and the length of QTc interval were not influenced by 5-HTTLPR polymorphism. There were no significant relations between HR and 5-HTT binding in the brain. There were significant associations between QTc interval and nor-β-CIT binding in the brain in l homozygotes, but not in s carriers (correlations for QTc interval and nor-β-CIT binding of striatum, thalamus and right temporal region were −0.8–−0.9, (p<0.0005), respectively).ConclusionThe finding of longer QTc interval with less 5-HTT binding availability in major serotonergic binding sites in l homozygotes, but not in s carriers, implicate to differentiated control of QTc interval by 5-HTTLPR polymorphism.