Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients.

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH(2)O pressure). The second months' alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable. There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd 8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9- -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4) versus sham (-0.3), and difference -1.2 (95% CI -2.0- -0.4), but no change in objective sleepiness. In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.     

Sex differences in the rate dependence of the T wave descending limb

OBJECTIVE: The interval from the peak to the end of the T wave (TpTe) has been proposed to reflect the heterogeneity of action potential durations within the ventricular wall. Several studies have previously described TpTe to be independent of heart rate, which contradicts the in vitro observation of marked changes in transmural repolarisation heterogeneity due to cycle length changes. Because of this inconsistency, we investigated heart rate related changes of TpTe interval. METHODS: During 24-h recordings (SEER MC, Marquette GE) in healthy young women (n=25, 26+/-7 years) and men (n=25, 27+/-8 years), a 10-s 12-lead ECG was obtained every 30 s. Recordings were repeated after 1 day, 1 week, and 1 month and results in each subject were pooled together and grouped for women and men. The QT and QT(peak) intervals were obtained automatically using QT Guard software (Marquette) and TpTe was computed as the difference between QT and QT(peak). In each subject TpTe values were averaged over 10-ms RR interval bands from 550 to 1150 ms. RESULTS: In both sexes, TpTe interval showed marked rate dependence with prolongation at long RR intervals. TpTe intervals in men were significantly longer over the entire range of investigated RR intervals (P=1.4x10(-25)). However, whereas the difference between sexes was marked at short cycle length (RR interval bin 540-550 ms: women 87+/-5 vs. men 95+/-9, P=5.1x10(-4)) it decreased at long cycle lengths (RR interval bin 1140-1150 ms: women 99+/-5 vs. men 106+/-6, P=9.3x10(-4)). CONCLUSION: There is a marked rate dependence of TpTe interval, which differs between women and men. The finding is consistent with the TpTe interval being an approximate surrogate of the intraventricular repolarisation gradient. The rate dependent increase in transmural repolarisation heterogeneity might be one of the reasons for the increased propensity of torsades de pointes in women.     

Increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease

BACKGROUND: Approximately half of patients with end-stage renal disease die because of cardiac disease, and ventricular arrhythmias are the common terminal events. Increased dispersion of the repolarization phase of the myocardial action potential can predispose patients to ventricular tachycardia and fibrillation causing cardiac death. OBJECTIVE: To determine the existence of increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease. STUDY DESIGN: Case-control prospective study. PATIENTS AND METHODS: The QT dispersion and the interval between the peak of the T wave (Tp) and the end of the T wave (Te) on a surface electrocardiogram represent regional and transmyocardial dispersion in ventricular repolarization, respectively. The prehemodialysis QT dispersions and Tp-Te intervals of 94 consecutive patients with end-stage renal disease were determined and compared with those of age- and sex-matched healthy controls. RESULTS: Both the QT and the QTc dispersion were significantly higher in the end-stage renal disease group than in the control group (QT dispersion 46 +/- 17 ms [mean +/- SD] versus 26 +/- 16 ms, P < 0.001; QTc dispersion 51 +/- 20 ms versus 30 +/- 20 ms, P < 0.001). Similarly, both the corrected average Tp-Te and the corrected maximum Tp-Te intervals were significantly higher in the end-stage renal disease group than in the control group (corrected average Tp-Te interval 99 +/- 19 ms versus 87 +/- 19 ms, P = 0.023; corrected maximum Tp-Te interval 114 +/- 23 ms versus 103 +/- 23 ms, P = 0.023). CONCLUSIONS: Increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease was demonstrated. This increased dispersion may be a contributory factor in the high cardiac mortality in patients with end-stage renal disease.     

Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study.

AIMS: We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. METHODS AND RESULTS: In this randomized and cross-over trial, 23 middle-aged OSA (apnoea-hypopnoea index, 44.1 +/- 29.3 h(-1)) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8 +/- 8.8 vs. 23.4 +/- 4.1 mmHg, respectively, P = 0.036). Ten out of 23 patients [43%, (95% CI: 23-64%)] and none of the control subjects had PH at baseline (P = 0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9 +/- 8.6 to 24.0 +/- 5.8 mmHg, P < 0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. CONCLUSION: Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.     

Relation of ventricular repolarization to cardiac cycle length in normal subjects, hypertrophic cardiomyopathy, and patients with myocardial infarction.

BACKGROUND: Prolonged QT interval and QT dispersion have been reported to reflect an increased inhomogeneity of ventricular repolarization, which is believed to be responsible for the development of arrhythmic events in patients with long QT syndrome, coronary heart disease, and myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy (HC). HYPOTHESIS: This study was undertaken to determine whether an abnormal QT/RR dynamicity may reflect autonomic imbalance and may contribute to arrhythmogenesis in patients with heart disease. METHODS: The relation between QT, QTpeak (QTp), Tpeak-Tend (TpTe) intervals and cardiac cycle length was assessed in 70 normal subjects, 37 patients with HC, and 48 survivors of myocardial infarction (MI). A set of 10 consecutive electrocardiograms was evaluated automatically in each subject using QT Guard software (Marquette Medical Systems, Milwaukee, Wisc.). RESULTS: In patients with HC, all intervals were significantly prolonged compared with normals (p < 0.001 for QT and QTp; p < 0.04 for TpTc); in survivors of MI, this was true for the maximum QT and QTp intervals (p < 0.05). A strong linear correlation between QT, QTp, and RR intervals was observed in normals and in patients with MI and HC (r = 0.65-0.59, 0.82-0.77, 0.79-0.74, respectively, p < 0.0001). TpTe interval only showed a weak correlation with heart rate in normals (r = 0.24, p < 0.05) and was rate-independent in both patient groups (p = NS). Compared with normals, the slopes of QT/RR and QTp/RR regression lines were significantly steeper in patients with MI and HC (0.0990-0.0883, 0.1597-0.1551, 0.1653-0.1486, respectively). Regression lines were neither parallel nor identical between normals and patients (T > 1.96, Z > 3.07). There was no difference in steepness for TpTeR/RR lines between groups (0.0110, 0.0076, 0.0163, respectively). TpTe/QTp ratio was similar in normals and in patients with MI and HC (0.30 +/- 0.03, 0.31 +/- 0.07, 0.30 +/- 0.04, respectively), in the absence of any correlation between QTp and TpTe intervals, suggesting disproportional prolongation of both components of QT interval. CONCLUSION: Compared with normals, a progressive increase in QT and QTp intervals at slower heart rates in patients with MI and HC may indicate an enhanced variability of the early ventricular repolarization and may be one of the mechanisms of arrhythmogenesis.     

Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: A systematic review and meta‐analysis

Obstructive sleep apnoea (OSA) is a prevalent sleep‐related breathing disorder associated with adverse cardiovascular outcome. Endothelial dysfunction is one of the proposed mechanistic links between OSA and the increased cardiovascular risk. Treatment with continuous positive airway pressure (CPAP) may reverse this detrimental pathophysiological consequence of OSA. Most studies on the effect of CPAP on endothelial function in OSA are limited by their low sample size. The objective of this systematic review was to assess the effect CPAP therapy on endothelial function in patients with OSA. We conducted a systematic review and meta‐analysis searching literature databases up to August 2013 for randomized controlled trials (RCTs) on the effect of CPAP on endothelial function in OSA, assessed by flow‐mediated dilatation (FMD) and other validated techniques. The primary outcome for the meta‐analysis (DerSimonian/Laird random‐effects method) was the treatment effect on FMD. Eight RCTs comparing the effects of therapeutic CPAP versus subtherapeutic CPAP (or no intervention) on endothelial function involving 245 OSA patients were included in the systematic review. The studies are consistent in effect direction, showing an improvement of endothelial function by CPAP. Four RCTs involving 150 patients could be used for the meta‐analysis. Compared to the control group, CPAP therapy (range 2–24 weeks) significantly increased absolute % FMD by 3.87% (95% confidence interval: 1.93–5.80, P < 0.001). In patients with OSA, CPAP therapy improves endothelial function significantly and to a clinically important extent.     

Auto-titrating continuous positive airway pressure therapy in patients with chronic heart failure and obstructive sleep apnoea: a randomized placebo-controlled trial.

AIMS: Obstructive sleep apnoea (OSA) is highly prevalent in patients with chronic heart failure (CHF) and may contribute to CHF progression. We aimed to determine whether treatment of OSA with continuous positive airway pressure (CPAP) would improve subjective and objective measures of heart failure severity in patients with CHF and OSA. METHODS AND RESULTS: Twenty-six patients with stable symptomatic CHF and OSA were randomized to nocturnal auto-titrating CPAP or sham CPAP for 6 weeks each in crossover design. Study co-primary endpoints were changes in peak VO(2) and 6 min walk distance. Secondary endpoints were changes in left ventricular ejection fraction, VE/VCO(2) slope, plasma neurohormonal markers, and quality-of-life measures. Twenty-three patients completed the study protocol. Mean CPAP and sham CPAP usage were 3.5 +/- 2.5 and 3.3 +/- 2.2 h/night, respectively (P = 0.31). CPAP treatment was associated with improvements in daytime sleepiness (Epworth Sleepiness Score 7 +/- 4 vs. 8 +/- 5, P = 0.04) but not in other quality-of-life measures. There were no changes in other study endpoints. CONCLUSION: In patients with CHF and OSA, auto-titrating CPAP improves daytime sleepiness but not other subjective or objective measures of CHF severity. These data suggest that the potential therapeutic benefits of CPAP in CHF are achieved by alleviation of OSA rather than by improvement in cardiac function.     

Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment

Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) <10 events · h(-1); 39 had an AHI between 10 and 19 events · h(-1) and 96 had an AHI ≥ 20 events · h(-1). CPAP treatment was offered when AHI was ≥ 20 events · h(-1). Patients were followed up for 7 yrs and incident CVE data were recorded. The mean ± SD age of the subjects was 73.3 ± 11 yrs; mean AHI was 26 ± 16.7 events · h(-1). Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥ 20 events · h(-1); n = 68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease (AHI 10-19 events · h(-1); n = 36) and patients without OSA (AHI <10 events · h(-1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.     

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.     

Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study.

AIMS: Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT intervals. Here, we evaluate variability of QT intervals in patients with a history of drug-induced long QT syndrome (dLQTS) and TdP in absence of a mutation in any of the major LQTS genes. METHODS AND RESULTS: Twenty patients with documented TdP under drugs with QT-prolonging potential were compared with 20 matched control individuals. An observer blinded to diagnosis manually measured lead-II, RR, and QT intervals from 30 consecutive beats. BVR was determined from Poincaré plots of QT intervals as short-term variability (STV(QT) = Sigma|QT(n)(+1) - QT(n)|/[30 x radical2]). QRS interval and cycle length was comparable between study groups and controls. No difference was found in QTc between dLQTS and controls (428 +/- 25 vs. 421 +/- 34 ms, P = 0.26), whereas STV(QT) was significantly higher in dLQTS when compared with controls (8.1 +/- 3.7 vs. 3.6 +/- 1.3 ms, P = 0.001). Proarrhythmic predictive power of STV(QT) was superior to that of the QTc interval (AUC: 0.89 vs. 0.57, 95% CI: 0.79-0.99 vs. 0.39-0.75). CONCLUSION: In the absence of QTc prolongation, baseline STV(QT) characterized patients with documented drug-induced proarrhythmia. STV(QT) could prove to be a useful non-invasive, easily obtainable parameter aiding the identification of the patient at risk for potentially life threatening arrhythmia in the context of drugs with QT prolonging potential.     

Long-term effect of continuous positive airway pressure on BP in patients with hypertension and sleep apnea

OBJECTIVE: To analyze the long-term effect of continuous positive airway pressure (CPAP) on ambulatory BP in patients with obstructive sleep apnea (OSA) and hypertension, and to identify subgroups of patients for whom CPAP could be more effective. METHODS: We conducted a prospective, long-term follow-up trial (24 months) in 55 patients with OSA and hypertension (mean CPAP use, 5.3 +/- 1.9 h/d [+/- SD]). Twenty-four-hour ambulatory BP monitoring (ABPM) was measured at baseline and after intervention with CPAP on an intention-to-treat basis. In addition, the correlation between the changes in 24-h mean arterial pressure (24hMAP) and CPAP compliance, OSA severity, and baseline ABPM was assessed. RESULTS: At the end of follow-up, a significant decrease was shown only in diastolic BP (- 2.2 mm Hg; 95% confidence interval [CI], - 4.2 to - 0.1; p = 0.03) but not in 24hMAP or other ABPM parameters. However, a correlation between changes in 24hMAP and baseline systolic BP (r = - 0.43, p = 0.001), diastolic BP (r = - 0.38, p = 0.004), and hours of use of CPAP (r = - 0.30, p = 0.02) was observed. A significant decrease in the 24hMAP was achieved in a subgroup of patients with incompletely controlled hypertension at entry (- 4.4 mm Hg; 95% CI, - 7.9 to - 0.9 mm Hg; p = 0.01), as well as in those with CPAP compliance > 5.3 h/d (- 5.3 mm Hg; 95% CI, - 9.5 to - 1.2 mm Hg; p = 0.01). Linear regression analysis showed that baseline systolic BP and hours of CPAP were independent predictors of reductions in BP with CPAP. CONCLUSION: Long-term CPAP reduced BP modestly in the whole sample. However, patients with higher BP at entry and good CPAP compliance achieved significant reductions in BP.     

The role of the expiratory phase in obstructive sleep apnoea.

The role of the expiratory phase in obstructive sleep apnoea (OSA) is not well known. The aim of our study was to verify the contribution of expiratory narrowing to apnoea in a group of OSA patients by evaluating the effects of short-term treatment with continuous positive airway pressure (CPAP), intermittent positive pressure ventilation (IPPV) and bi-level positive airway pressure (BIPAP). We studied a selected group of 10 OSA patients whose therapeutic pressure level of CPAP was at least 10 cm H2O. During CPAP therapy the mean apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) decreased from 64.8 to 6.3 (P < 0.001) and from 58.5 to 6.1 (P < 0.001), respectively and mean nadir SAO2 increased from 62.0 to 91.6 (P < 0.001). None of the patients reached optimal setting (elimination of snoring, reduction of apnoeas and non-apnoeic desaturation events at least to 15 or less per hour of sleep and maintenance of oxygen saturation approximately 90%) during IPPV and two patients did not tolerate final IPAP pressure levels. When a critical level of EPAP (BIPAP) was applied in the same night to these patients, optimal setting was reached in all subjects. During BIPAP, mean AHI decreased from 64.8 to 7.4 (P < 0.001); ODI decreased from 58.5 to 7.6 (P < 0.001) and nadir SAO2 increased from 62.0 to 91.2 (P < 0.001). Our study confirms the essential role of a critical level of EPAP in successful ventilatory treatment in OSA, thereby indicating, in agreement with few previous studies, the critical role of end of expiratory occlusion in OSA pathogenesis.     

Is myocardial repolarization duration associated with repolarization heterogeneity?

Background

Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate‐corrected J‐to‐T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe).

Methods

A retrospective cohort study was performed at a single urban tertiary ED from July 2011–September 2012. Inclusion criteria included all consecutive ED patients with ECG based on QTc and QRS intervals. Automated measurements of all intervals were performed. The association of JTpkc with the dependent variable TpTe was assessed after adjustment for QRS and RR interval durations with a multiple linear regression model. A secondary analysis included a similar adjusted assessment of the association of JTpkc with QT dispersion, QTd. Finally, we constructed two multiple regression models to assess the association of clinical causative factors of TdP with TpTe and JTpkc.

Results

Eight hundred seventy‐four cases were included: 186 with QTc <500 ms, 118 with QTc ≥500 and QRS ≥120 ms, and 570 with QTc ≥500 and QRS <120 ms. The coefficient for association of JTpkc with TpTe was ?0.10 (95%CI ?0.15 to ?0.05), and for JTpkc with QTd was 0.03 (95% CI ?0.01 to 0.06). Clinical causative TdP factors were associated more with JTpkc than TpTe.

Conclusion

Repolarization duration as measured by JTpkc is not positively associated with dispersion of repolarization as measured by TpTe or QTd. Dispersion of repolarization may not be a critical mechanistic link between QTc prolongation and TdP.

     

Short-term repeatability of electrocardiographic Tpeak–Tend and QT intervals

Background

The electrocardiographic (ECG) Tpeak–Tend interval (TpTe) is associated with arrhythmias and sudden cardiac death. TpTe offers a supplementary measure for the QT interval (QT), yet its repeatability has not been established.

Purpose

Evaluate short-term repeatability of TpTe and QT.

Methods

Four ECGs were obtained on sixty participants. The sources of variation, intra-class correlation coefficient (ICC) – an index of reproducibility – and minimal detectable change (MDC) were estimated for TpTe and QT. The impact of repeated measurements on repeatability was estimated for a hypothetical clinical trial designed to detect drug-induced prolongation of TpTe and QT.

Results

We used heart rate-adjusted QT [(QT)a] but TpTe in the study group was rate-invariant. The ICC [95% confidence interval (CI)] was 0.77 (0.69, 0.85) for TpTe, 0.75 (0.65, 0.85) for QT and 0.60 (0.47, 0.73) for (QT)a. The MDC (ms) was 21, 32 and 26 for TpTe, QT and (QT)a respectively.

Conclusion

TpTe has excellent repeatability supporting its use as a supplement to QT in observational and clinical studies.     

Circadian and Gender Effects on Repolarization in Healthy Adults: A Study Using Harmonic Regression Analysis

Background: Sudden cardiac death and myocardial infarction have a circadian variation with a peak incidence in the early morning hours. Increased dispersion of repolarization facilitates the development of conduction delay necessary to induce sustained arrhythmia. Both QT‐dispersion and T‐wave peak to T‐wave end (TpTe) have been proposed as markers of dispersion of myocardial repolarization. Methods: Forty healthy adults (20 women), age 35–67 years old, with normal EKGs, echocardiograms, stress tests, and tilt‐table tests were analyzed during a 27‐hour hospital stay. EKGs were done at eight different time points. QT‐intervals, QT‐dispersion, and TpTe were measured at each time point. Harmonic regression was used to model circadian periodicity, P < 0.05 was considered significant. Results: The composite QT‐interval was longer in women than in men (416 ± 17 msec vs 411 ± 20 msec, respectively, P = 0.006). The QT‐dispersion among all leads was greater in men than women (37 ± 13 msec vs 30 ± 11 msec, respectively, P < 0.0001); a similar difference was found in the precordial leads. Harmonic regression showed that QT‐dispersion had a significant circadian variation, primarily in men. In men, the maximum QT‐dispersion occurred at 6 AM (45 ± 15 msec). TpTe also had a significant circadian variation that was not affected by gender in the majority of leads. Conclusions: A circadian variation exists in the dispersion of myocardial repolarization, as measured by both TpTe and QT‐dispersion. Men and women have a different circadian variation pattern. Further studies regarding the mechanisms and clinical implications are needed. Ann Noninvasive Electrocardiol 2010;15(1):3–10     

QT dispersion and late potentials during doxorubicin therapy for non-Hodgkin's lymphoma

OBJECTIVES: To investigate effects of doxorubicin therapy on cardiac electrophysiology, with special emphasis on QT dispersion and late potentials, in lymphoma patients. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult non-Hodgkin's lymphoma patients who received doxorubicin to a cumulative dose of 400-500 mg m-2. MAIN OUTCOME MEASURES: Standard 12-lead electrocardiogram (ECG) and signal-averaged ECG (SAECG) recordings were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m-2. RESULTS: Heart rate-corrected QT interval (QTc) increased from 402 +/- 4 to 416 +/- 5 ms (P = 0.002) during the study period. QT dispersion (variability in QT interval duration amongst the different leads of the standard 12-lead ECG) increased from 24.1 +/- 2.5 to 35.0 +/- 2.8 ms (P = 0.041) and QTc dispersion increased from 26.5 +/- 2.5 to 39.0 +/- 3.5 ms (P = 0.039). Five patients (18%) developed QT dispersion exceeding 50 ms. In addition, two patients (7%) developed late potentials during doxorubicin therapy. The changes in QTc duration, QT dispersion and late potentials occurred independently of the impairment of left ventricular function. CONCLUSIONS: Prolongation of QTc, increased QT dispersion and development of late potentials are indicative of doxorubicin-induced abnormal ventricular depolarization and repolarization. QT dispersion and late potentials are both known to be associated with increased risk of serious ventricular dysrhythmias and sudden death in various cardiac diseases. Thus, follow-up of these parameters might also be useful in assessing the risk of late cardiovascular events in cancer patients treated with anthracyclines.     

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.     

Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans.

OBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk. BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects. METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories. RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88). CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.     

Relation of QTc duration heterogeneity to mortality following orthotopic heart transplantation

Studies of heart failure patients have demonstrated that serial QT prolongation and abnormally prolonged QT intervals are associated with greater mortality. Serial QT interval measurements in patients who undergo orthotopic heart transplantation (OHT) may quantify the degree of myocardial repolarization heterogeneity and serve as a marker of arrhythmogenic substrate. In this study, the mean survival for those with "stable" QT(c) intervals (a change of -10 to 10 ms/year) was 124 +/- 8 months versus 63 +/- 25 months in those with annual QT(c) changes of >10 ms (p = 0.009). Ventricular repolarization heterogeneity may serve as a marker of identifying high-risk patients after OHT.     

In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine.

OBJECTIVES/BACKGROUND: Previous in vitro studies have suggested full repolarization of the epicardium coincides with the peak of the T wave (T(peak)) and that of the M cells coincides with the end of the T wave (T(end)). However, in vivo validation of the theory is lacking. METHODS: Monophasic action potentials (MAPs) were recorded using the CARTO mapping system from 51 +/- 10 epicardial sites and 64 +/- 9 endocardial sites of the left ventricle in 10 pigs and from 41 +/- 4 epicardial sites and 53 +/- 2 endocardial sites of the right ventricle in two of the 10 pigs. End of repolarization (EOR) times over the epicardium (EOR(epi)), endocardium (EOR(endo)), and over both (EOR(total)) were obtained. QT(peak) and QT(end) intervals were measured from simultaneously recorded 12-lead ECG. RESULTS: Minimal and maximal EOR(total) were observed in the left ventricle in all pigs. Minimal EOR(total) was on the epicardium in five pigs, and maximal EOR(total) was on the endocardium in nine pigs. Minimal, mean, and maximal QT(peak) intervals all were significantly smaller than maximal EOR(epi) (322 +/- 23 ms, P <.01). No significant difference was found between maximal QT(end) interval (338 +/- 30 ms) and maximal EOR(endo) (339 +/- 24 ms, difference = 1 +/- 19 ms, P =.92), between maximal QT(end) interval and maximal EOR(total) (341 +/- 24 ms, difference = 2 +/- 18 ms, P =.69), or between minimal QT(peak) interval (283 +/- 28 ms) and minimal EOR(total) (282 +/- 20 ms, difference = 0 +/- 15 ms, P =.95). CONCLUSIONS: In in vivo pig models, T(peak) does not coincide with full repolarization of the epicardium but coincides well with the earliest EOR, whereas the T(end) corresponds with the latest EOR. These findings suggest that not only the transmural gradients but also the apicobasal repolarization gradients contribute to genesis of the T wave.