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AbstractBackground In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls.Patients and Methods In this substudy of the international multicenter case–control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18–49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status.Results 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20–12.42), in participants without antihypertensives (4.86; 1.07–22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47–36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37–17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged.Conclusions Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Purpose: Hyperkyphosis, accentuated curvature of the thoracic spine, is often attributed to osteoporosis, yet its underlying pathophysiology is not well understood. Bone turnover markers (BTM) reflect the dynamic process of bone formation and resorption. This study examined the association between serum BTM levels and kyphosis in community-dwelling older adults. Methods: Between 2003 and 2006, 760 men and women in the Rancho Bernardo Study age 60 and older had blood drawn and kyphosis measured. Fasting serum was assayed for N-telopeptide (NTX) and procollagen type 1 n-terminal propeptide (P1NP), markers of bone resorption and formation, respectively. Participants requiring two or more 1.7 cm blocks under their head to achieve a neutral supine position were classified as having accentuated kyphosis. Analyses were stratified by sex and use of estrogen therapy (ET). Odds of accentuated kyphosis were calculated for each standard deviation increase in log-transformed BTM. Results: Mean age was 75 years. Overall, 51% of 341 non-ET using women, 41% of 111 ET-using women, and 75% of 308 men had accentuated kyphosis. In adjusted models, higher P1NP and NTX were associated with decreased odds of accentuated kyphosis in non-ET using women (P1NP: OR = 0.78 [95% CI, 0.58–0.92]; NTX: OR = 0.68 [95% CI, 0.54–0.86]), but not in men or ET-using women (p > 0.05). Conclusions: The selective association of higher bone turnover with reduced odds of accentuated kyphosis in non-ET using women suggests that elevated BTM were associated with a lower likelihood of hyperkyphosis only in the low estrogen/high BTM environment characteristic of postmenopausal women who are not using ET. Keywords: Kyphosis, Hyperkyphosis, Bone turnover, Bone remodeling, P1NP, NTX

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Objective: To describe the nutritional status in patients with screen-detected celiac disease (CD).Methods: Nutritional status was assessed by serum tests and anthropometric measures in 26 subjects (16 to 25 years of age) with biopsy-proven CD and 29 healthy control subjects (16 to 21 years of age) with negative tissue transglutaminase antibodies (16 to 22 years of age); all the subjects were selected from the cohort of 3654 schoolchildren.Results: Compared with control subjects, CD patients had lower median values of whole blood folic acid (91 versus 109 nmol/L; P = 0.01), serum ferritin (14 versus 27 microg/L; P = 0.028) and pre-albumin (0.21 versus 0.28 g/L; P Conclusions: One third of screen-detected adolescent CD subjects have abnormalities in folate or iron status that call for early diagnosis and dietary treatment of the disease to prevent nutritional deficiencies. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To describe the nutritional status in patients with screen-detected celiac disease (CD).METHODS:: Nutritional status was assessed by serum tests and anthropometric measures in 26 subjects (16 to 25 years of age) with biopsy-proven CD and 29 healthy control subjects (16 to 21 years of age) with negative tissue transglutaminase antibodies (16 to 22 years of age); all the subjects were selected from the cohort of 3654 schoolchildren.RESULTS:: Compared with control subjects, CD patients had lower median values of whole blood folic acid (91 versus 109 nmol/L; P = 0.01), serum ferritin (14 versus 27 μg/L; P = 0.028) and pre-albumin (0.21 versus 0.28 g/L; P ≤ 0.001) and higher transferrin receptor (1.3 versus 1.1; P = 0.008) and serum transferrin receptor-ferritin index (1.2 versus 0.7; P = 0.006). Folic acid concentration was subnormal in 31% of the CD subjects (versus 14% of the controls) and iron status (transferrin receptor-ferritin index) was subnormal in 30% (versus 14%). Body mass index was not different in females of the CD and control groups (22 versus 22 kg/m) or in the males of the respective groups (25 versus 24 kg/m). Females with CD were shorter than the controls (mean 162 versus 167 cm; P = 0.018), but no difference was found in males. No association was found between the nutritional status and the markers of mucosal injury (villous-crypt measures), but titer of transglutaminase was associated with whole blood folic acid (r = −0.5; P = 0.016) and with transferrin receptor-ferritin index (r = 0.4, P = 0.05).CONCLUSIONS:: One third of screen-detected adolescent CD subjects have abnormalities in folate or iron status that call for early diagnosis and dietary treatment of the disease to prevent nutritional deficiencies. [ABSTRACT FROM AUTHOR]

Background: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls., Patients and Methods: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status., Results: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged., Conclusions: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Introduction: Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders., Methods: Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia., Results: A late increase of lactate about three times the basal level was seen 10-30 min after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease., Discussion: Our results suggest that follow-up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases.

Cardiovascular diseases are the leading cause of mortality in both men and women, but in women these diseases manifest at a later age. After menopause, the decline in estrogen levels accelerates key atherogenic processes, including dyslipidemia, endothelial dysfunction and arterial stiffening, increasing the risk for cardiovascular events. In the healthy vasculature, estrogen has several structural and functional protective effects. The primary indication for menopausal hormone therapy is the treatment of climacteric symptoms, in particular hot flashes. With appropriate timing of estrogen treatment, it is possible to improve the ageing women's vascular health.

Objective: To compare in controlled cardiovascular autonomic function tests the effects of hormone therapy (HT) on heart rate variability (HRV) responses in postmenopausal women with and without pretreatment hot flushes., Design: A randomized placebo-controlled trial., Setting: Finland, Helsinki University Central Hospital., Population: A total of 150 recently postmenopausal and healthy women with prospectively evaluated hot flushes., Methods: Women (72 with and 78 without hot flushes) were randomized to receive estradiol alone or in combination with medroxyprogesterone acetate or placebo for 6 months. Time and frequency domain measures of HRV were assessed at baseline and after HT with short-term recordings during paced quiet and deep breathing and with active orthostatic tests, both under carefully controlled laboratory conditions to avoid confounding factors present in long-term ambulatory HRV measurements., Main Outcome Measures: Responses of time and frequency domain measures of HRV to HT., Results: At baseline HRV was similar in women with and without hot flushes. Pretreatment hot flushes did not associate with changes in time domain parameters of HRV during controlled quiet or deep breathing or active orthostatic tests after different types of HT. However, HT reduced HRV in very low frequency power in women with pretreatment hot flushes (from 371 ± 40 to 258 ± 28 ms(2) , p = 0.018). HT did not have an effect on other frequency domain measures during quiet breathing or active orthostatic tests., Conclusions: Hormone therapy did not significantly modify the HRV responses in women with or without hot flushes under controlled short-term measurements of the cardiovascular autonomic nervous system., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background:   LQT1 subtype of long QT syndrome is characterized by defective I(Ks) , which is intrinsically stronger in the epicardium than in the midmyocardial region. Electrocardiographic QT peak and QT end intervals may reflect complete repolarization of epicardium and midmyocardial region of the ventricular wall, respectively. Repolarization abnormalities in LQT1 carriers may therefore be more easily detected in the QT peak intervals., Methods:   Asymptomatic KCNQ1 mutation carriers (LQT1, n=9) and unaffected healthy controls (n=8) were studied during Valsalva manoeuvre, mental stress, handgrip and supine exercise. Global QT peak and QT end intervals derived from 25 simultaneous electrocardiographic leads were measured beat to beat with an automated method., Results:   In unaffected subjects, the percentage shortening of QT peak was greater than that of QT end during mental stress and during the recovery phases of Valsalva and supine exercise. In LQT1 carriers, the percentage shortening of the intervals was similar. At the beginning of Valsalva strain under abrupt endogenous sympathetic activation, QT peak shortened in LQT1 but not in control patients yielding increased electrocardiographic transmural dispersion of repolarization in LQT1., Conclusions:   In asymptomatic KCNQ1 mutation carriers, repolarization abnormalities are more evident in the QT peak than in the QT end interval during adrenergic adaptation, possibly related to transmural differences in the degree of I(Ks) block., (© 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objectives: During menopausal transition autonomic balance is known to shift towards sympathetic dominance, but the role of vasomotor hot flushes in this phenomenon is not understood. We compared cardiovascular autonomic responsiveness between women with and without hot flushes., Study Design and Main Outcome Measures: One hundred fifty recently postmenopausal healthy women with varying degree of hot flushes (none, mild, moderate, severe) underwent comprehensive cardiovascular autonomic nervous testing (controlled and deep breathing, active orthostatic test, Valsalva manoeuvre and handgrip test) assessing both sympathetic and parasympathetic activity. The responses of heart rate, heart rate variability and blood pressure in these tests were evaluated., Results: Responses in heart rate showed differences between the study groups only in the Valsalva manoeuvre where the tachycardia ratio in all symptomatic women was lower (p=0.041) than in women without hot flushes. Neither change in the heart rate variability analyses nor the blood pressure responses were affected by hot flush status. However, there was a non-significantly higher maximum systolic (140 (112-182)mmHg vs. 135 (102-208)mmHg) and diastolic blood pressure (94 (72-112)mmHg vs. 90 (66-122)mmHg) following the handgrip test in women without hot flushes vs. all the symptomatic women., Conclusions: Menopausal hot flushes seem to be associated with a possibly increased sympathetic preponderance without an effect on parasympathetic activity in cardiovascular autonomic responses. This may imply a potentially negative impact on cardiovascular health in women experiencing hot flushes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Background: Blood pressure (BP) is one of the most powerful determinants of cardiovascular risk in women. This risk may differ between post-menopausal women with and without vasomotor hot flushes, possibly indicating different vascular responses to hormone therapy (HT). Thus, we compared in a clinical trial the effect of HT on ambulatory BP in normotensive, recently post-menopausal women with or without severe hot flushes., Methods: A total of 147 women recorded prospectively their hot flushes for 2 weeks; 70 women were symptomatic (>or=7 moderate/severe hot flush episodes/day), whereas 77 women were defined as asymptomatic (

Background: Menopausal hot flushes may be a marker for a difference in vascular function. We studied the associations between hot flushes of varying severity and ambulatory blood pressure (BP) and heart rate (HR)., Methods: A total of 147 women with onset of menopause within the preceding 6-36 months reported no hot flushes (n = 23) or mild (n = 33), moderate (n = 30), or severe (n = 61). Ambulatory BP and HR were registered for 24 hours. The variables, analyzed separately for day-time and night-time, were compared among the four study groups., Results: Hot flushes failed to show any relationship to mean day- or night-time BP, nocturnal dipping of BP, or HR. However, severe night-time hot flushes were accompanied by elevations in systolic BP (4.1 +/- 10.5 mmHg, P = 0.061), diastolic BP (3.1 +/- 6.8 mmHg, P = 0.032), and heart rate (3.0 +/- 7.2 beats/minute, P = 0.043)., Conclusion: Hot flushes are not associated with ambulatory BP or heart rate in normotensive, recently post-menopausal women, although severe night-time hot flush episodes are followed by significant elevations in BP and heart rate. The latter may be of clinical significance.

Objective: To compare the vascular responses to hormone therapy in women with and without hot flushes., Methods: We randomly assigned 143 healthy, recently postmenopausal women (mean age 52.4+/-0.2 years, time since menopause 19.5+/-0.9 months) with intolerable hot flushes (more than seven moderate/severe episodes per day) or tolerable hot flushes (fewer than three mild episodes per day) to receive 1 mg of transdermal estradiol gel, oral estradiol (2 mg) with and without daily medroxyprogesterone acetate, or placebo for 6 months. Vascular function was assessed by pulse-wave analysis and endothelial function testing with nitroglycerin and salbutamol challenges., Results: Hot flushes did not affect the changes in arterial or aortic stiffness or endothelial function in response to various forms of hormone therapy. However, in women with tolerable hot flushes, oral estradiol caused a decrease of 13.2% (P=.028) in the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) after nitroglycerin. In addition, the time to the reflected wave (dependent on pulse-wave velocity) after nitroglycerin was decreased by 8.4% (P=.018). These effects were not seen in women with intolerable hot flushes or with the other treatment regimens., Conclusion: Women without troublesome hot flushes are susceptible to unfavorable vascular effects after oral estrogen treatment, resulting in less compliant vasculature., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00668603., Level of Evidence: I.

Objective: Observational studies indicate that postmenopausal hormone therapy (HT) prevents cardiovascular disease, but randomized clinical trials have not confirmed this effect. Hot flushes were more likely to be present in women starting HT in observational studies, whereas these symptoms were mild or absent among women attending randomized clinical trials. We hypothesized that vascular function may differ in women with and without vasomotor hot flushes., Methods: One hundred forty-three recently postmenopausal women showing a broad range of variation in hot flushes were studied with radial artery tonometry. Pulse wave analyses were assessed at baseline and after nitroglycerin and salbutamol challenges. Wilcoxon signed rank test was used for paired comparisons after challenges with nitroglycerin and salbutamol., Results: Neither baseline arterial stiffness nor endothelial function differed between women without or with mild, moderate, or severe hot flushes. However, after nitroglycerin challenge, the time to the onset of the reflected wave (dependent on pulse wave velocity) was 9.5% longer (P=.014), and the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) was 13.9% longer (P=.025) in women with severe hot flushes as compared with asymptomatic women., Conclusion: Women with severe vasomotor hot flushes show greater vascular responsiveness to nitroglycerin than women without hot flushes. This may partially explain the conflicting data between observational and randomized HT studies., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00668603, Level of Evidence: II.

Objectives: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) experience exercise-related malignant arrhythmias possibly based on delayed repolarization in the diseased right ventricle (RV). Autonomic interventions might unveil repolarization abnormalities in RV., Design: We recorded 25-lead electrocardiograms from nine symptomatic ARVC patients and nine controls during rest, Valsalva maneuver, mental stress, handgrip and supine exercise. Interventricular repolarization gradient was defined as difference of QT intervals between left ventricular (LV) and RV type leads. T-wave peak to T-wave end interval (TPE) was defined as the electrocardiographic (ECG) equivalent of transmural dispersion of repolarization., Results: ARVC patients showed longer QT and TPE intervals in RV than in LV whereas control subjects showed the opposite. Valsalva strain reversed the interventricular repolarization gradient from -5+/-13 to 4+/-20 ms (p<0.02) and induced fluctuation of TPE in ARVC patients., Conclusions: ARVC patients show ECG interventricular repolarization gradient from RV to LV and increased ECG transmural dispersion of repolarization in RV. Valsalva strain induces fluctuation of interventricular repolarization gradient and of transmural dispersion of repolarization in RV possibly modifying the substrate for arrhythmias.

Objectives: In LQT1 subtype of inherited long QT syndrome, repolarization abnormalities originating from defective I(Ks) render patients vulnerable to ventricular arrhythmia during sudden sympathetic activation. Experimental studies show lower I(Ks) density and longer action potential duration in left (LV) than in right (RV) ventricle. We studied interventricular dispersion of repolarization in patients with I(Ks) defect during autonomic tests., Design: We measured interventricular (difference of QT intervals between LV and RV type leads) and transmural electrocardiographic dispersion of repolarization from 25-lead electrocardiograms in nine asymptomatic KCNQ1 mutation carriers (LQT1) and eight controls during rest, Valsalva maneuver, mental stress, sustained handgrip and supine exercise., Results: LQT1 carriers showed increased interventricular dispersion of repolarization (13+/-9 ms vs. 4+/-4 ms, p=0.03) during all tests. Valsalva strain increased the difference between the study groups. In LQT1 carriers, interventricular dispersion of repolarization correlated weakly with electrocardiographic transmural dispersion of repolarization., Conclusions: Asymptomatic KCNQ1 mutation carriers exhibit increased and by abrupt sympathetic activation augmented interventricular difference in electrocardiographic repolarization times. Interventricular and transmural repolarization dispersion behave similarly in patients with I(Ks) defect.

Background: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients., Methods: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise., Results: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals--a QT overshoot--during the recovery phases. The number of tests with a QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups., Conclusions: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.

Aims: High-intensity physical exercise and competitive sports have been traditionally avoided in long QT syndrome. However, endurance training increases vagal activity and thus may improve cardiac electrical stability in healthy subjects. We hypothesized that controlled submaximal endurance training would not adversely affect ventricular repolarization in asymptomatic carriers of a KCNQ1 gene mutation of type 1 long QT syndrome (LQT1)., Methods and Results: Previously, sedentary carriers of a missense mutation of KCNQ1 gene (LQT1, n=7) and healthy controls (n=8) exercised on a bicycle ergometer 3-4 times a week, 30 min a day at 60-75% of maximal heart rate (HR) for a maximum of 3 months. Body surface potential mapping (BSPM) was recorded and QT intervals were determined automatically from 14 channels over the left chest area. Maximal work capacity increased by 4+/-1% in LQT1 and by 14+/-2% in controls (both P<0.05), and left ventricular (LV) mass by 8+/-1% and 9+/-1%, respectively (P<0.05). Resting corrected QT interval shortened by 10+/-1% (P<0.05) and QT interval dispersion by 25+/-9% (P<0.05) in LQT1, but not significantly in controls. QT intervals at specified HRs during workload and recovery phases were not changed in either group., Conclusion: In this pilot study of asymptomatic carriers of a KNCQ1 gene mutation, submaximal endurance training did not harmfully affect arrhythmia risk markers. Confirmatory studies in a broader spectrum of LQT1 genotypes are needed before any generalization can be made.