Renal denervation in patients who do not respond to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) reduces the morbidity and mortality in advanced heart failure (HF) in about two-thirds of the patients. Approximately one-third of the patients do not respond to CRT. The overactivity of sympathetic nervous system is associated with advanced HF and deteriorates the hemodynamic state. We tested the hypothesis that controlling sympathetic overactivity by renal denervation (RDN) could be beneficial in nonresponders for CRT. In our HeartF-RDN study (ClinalTrials.gov. NCT02638324), RDN could not reverse the progression of HF in subjects with New York Heart Association Classification (NYHA) III-IV stage symptoms.

Intravascular Renal Denervation in Renal Dialysis Patients with Uncontrolled Hypertension: A Case Series of Four Patients.

BACKGROUND Hypertension is a common complication of renal dialysis and is inadequately controlled in approximately one-third of patients. Intravascular renal denervation is an option to control sympathetic overdrive and decrease blood pressure. Four renal dialysis patients are presented with uncontrolled hypertension who were treated with intravascular renal denervation. CASE REPORT In a renal dialysis unit, patients were screened for therapy-resistant hypertension, which was defined as an outpatient blood pressure >160/100 mmHg and a blood pressure by interdialytic ambulatory blood pressure monitoring (ABPM) >130/80 mmHg. Four patients were identified with a mean ABPM of 175/95 mmHg. The four patients included a 24-year-old man with neurogenic bladder undergoing hemodialysis; a 55-year-old woman with a history of type 1 diabetes mellitus undergoing peritoneal dialysis; a 56-year-old woman with a history of autosomal dominant polycystic kidney disease (ADPKD) undergoing peritoneal dialysis; and a 72-year-old man with a history of ADPKD undergoing hemodialysis Following intravascular renal denervation, one patient had antihypertensive medicines withdrawn at 12 months, and he remained normotensive up to renal transplantation at 24 months. In two patients, ABPM did not decrease until renal transplantation was performed. The fourth patient was not a candidate for renal transplantation, and he was also a non-responder for intravascular renal denervation. None of the patients experienced hypotension or other adverse events following intravascular renal denervation. CONCLUSIONS A case series of four patients showed that, for some patients who have unresponsive hypertension while on renal dialysis, intravascular renal denervation is a safe procedure.

Renal sympathetic denervation in treating drug-resistant hypertension in a patient on hemodialysis.

A 26-year-old man had an end-stage renal disease because of a neurogenic urinary bladder with a vesicourinary reflux. The first kidney transplant was lost in consequence of chronic allograft nephropathy. Immunosuppressive medication was withdrawn and transplantectomy was performed in November 2010. After transplantectomy, his blood pressure (BP) slowly increased up to 200/100 mmHg. Antihypertensive medication was intensified and a fluid overload was excluded with body composition bioimpedance measurements. Forty-eight-hour ambulatory BP was 180/109 mmHg in the daytime and 178/108 mmHg in the night-time. Bilateral renal denervation (RDN) was performed with a single electrode Symplicity catheter on May 2013. The effect of RDN became evident at the 6 months visit, and all the antihypertensive medicines were withdrawn at 12 months. Fifteen months after RDN, 48-h ambulatory BP was 120/63 mmHg in the daytime and 108/60 mmHg in the night-time. The patient was without antihypertensive medication until retransplantation in May 2015.

Impaired negative chronotropic response to adenosine in patients with inappropriate sinus tachycardia.

INTRODUCTION: Adenosine is an endogenous nucleoside that has an important role in the diagnosis and treatment of several cardiac arrhythmias. However, its effects on inappropriate sinus tachycardia (IST) are not well established. METHODS AND RESULTS: In this study, the response to intravenous adenosine (0.1 to 0.15 mg/kg) was studied in 18 patients (age 46+/-15 years) with IST. In a subset of patients (n = 5), the direct effects of adenosine were assessed during pharmacologic beta-adrenergic and cholinergic blockade. Atrial cycle length (ACL) was measured before adenosine injection, at the time of the greatest cycle length prolongation, and during the maximum rebound acceleration of heart rate. Eighteen subjects (age 46+/-11 years) with normal sinus rhythm undergoing clinically indicated electrophysiologic study served as controls. Adenosine did not terminate IST in any patient. The maximum dose of adenosine prolonged the sinus interval significantly, from 780+/-128 msec to 985+/-225 msec (P < 0.001) in the control subjects. In contrast, adenosine caused no significant lengthening of atrial cycle length (527+/-69 msec vs 590+/-148 msec; P = NS) in the patients with IST. Similar difference in the response to adenosine was seen during the pharmacologic autonomic blockade. The reflex increase of the sinus rate (rebound effect) was greater in the control subjects than in the patients with IST (21.2%+/-9.7% vs 8.5%+/-8.8%; P < 0.001). CONCLUSION: The usual negative chronotropic effect of adenosine was impaired in the patients with IST. This may have important diagnostic implications and provide new insight into the mechanism(s) of IST.

Naltrexone suppresses ethanol intake in 6-hydroxydopamine-treated rats.

BACKGROUND: The suppressive effect of opioid antagonists, such as naltrexone, on ethanol intake has been suggested to be based on the interference with ethanol-induced stimulation of dopamine release in the nucleus accumbens. The aim of this study was to determine whether reduction of dopamine innervation to the nucleus accumbens with the neurotoxin 6-hydroxydopamine (6-OHDA) alters naltrexone-induced suppression of ethanol consumption. Because the mesolimbic dopaminergic neurons have also been implicated in ethanol reinforcement, the effects of 6-OHDA on the maintenance and acquisition of ethanol intake were also studied. METHODS: To damage accumbal terminals of the mesolimbic dopamine neurons, alcohol-preferring Alko Alcohol (AA) rats were given bilateral injections of 6-OHDA or vehicle into the nucleus accumbens after pretreatment with desipramine and pargyline. The effect of the lesion on the acquisition or maintenance of ethanol self-administration was studied in animals having continual access to ethanol solution (10% v/v) and water. Subsequently the effect of naltrexone on ethanol consumption was determined. RESULTS: Naltrexone (0.03-3.0 mg/kg subcutaneously) suppressed ethanol consumption in a dose-dependent manner both in 6-OHDA-treated and control animals given a daily 90-min access to ethanol solution. When the rats had continual access to ethanol, there was a clear day-to-day decline in ethanol intake during the first 5 days of the 7-day naltrexone treatment (10 mg/kg subcutaneously). 6-OHDA treatment had no effect on either the acquisition or maintenance of ethanol self-administration. Postmortem analysis of the brain dopamine content revealed approximately 92% depletion of dopamine in the nucleus accumbens of the 6-OHDA-treated rats. CONCLUSIONS: The suppressive effect of naltrexone does not depend on naltrexone's interaction with dopaminergic terminals in the nucleus accumbens. Furthermore, the role of the mesolimbic dopamine pathway is probably not central either in the acquisition or maintenance of ethanol self-administration in alcohol-preferring AA rats.

Dynamic behavior and autonomic regulation of ectopic atrial pacemakers.

BACKGROUND: Heart rate (HR) variability reflects the neural regulation of normal pacemaker tissue, but the autonomic nervous regulation of abnormal atrial foci originating outside the sinus node has not been well characterized. We compared the HR variability of tachycardias originating from the ectopic foci and the sinus node. METHODS AND RESULTS: R-R-interval variability was analyzed from 24-hour Holter recordings in 12 patients with incessant ectopic atrial tachycardia (average HR 107+/-14 bpm), 12 subjects with sinus tachycardia (average HR 106+/-9 bpm), and 24 age- and sex-matched subjects with normal sinus rhythm (average HR 72+/-8 bpm). Time- and frequency-domain HR variability measures, along with approximate entropy, short- and long-term correlation properties of R-R intervals (exponents alpha(1) and alpha(2)), and power-law scaling (exponent beta), were analyzed. Time- and frequency-domain measures of HR variability did not differ between subjects with ectopic and sinus tachycardia. Fractal scaling exponents and approximate entropy were similar in sinus tachycardia and normal sinus rhythm, but the short-term scaling exponent alpha(1) was significantly lower in ectopic atrial tachycardia (0.71+/-0.16) than in sinus tachycardia (1.16+/-0.13; P<0.001) or normal sinus rhythm (1.19+/-0.11; P<0.001). Abrupt prolongations in R-R intervals due to exit blocks from the ectopic foci or instability in beat-to-beat R-R dynamics were the major reasons for altered short-term HR behavior during ectopic tachycardias. CONCLUSIONS: HR variability obtained by time- and frequency-domain methods does not differ between ectopic and sinus tachycardias, which suggests that abnormal atrial foci are under similar long-term autonomic regulation as normal pacemaker tissue. Short-term R-R-interval dynamics are altered toward more random behavior in ectopic tachycardia, which may result from a specific autonomic disturbance or an intrinsic abnormality of ectopic atrial pacemakers.

Prevalence and natural course of ectopic atrial tachycardia.

AIMS: The purpose of this study was to calculate the prevalence of ectopic atrial tachycardia in a population of young asymptomatic males and to assess its natural course both in asymptomatic subjects and in symptomatic hospital patients. METHODS AND RESULTS: 12-lead electrocardiograms (ECG) of 3554 consecutive males applying for a pilot's licence were analysed. ECGs of symptomatic arrhythmia patients at two university hospitals were also analysed. A repeat ECG was taken in cases of ectopic atrial tachycardia to assess the natural course of this arrhythmia. Twelve out of 3554 asymptomatic subjects (prevalence 0.34%) and 17 out of 3700 symptomatic arrhythmia patients (prevalence 0.46%) had ECG evidence of ectopic atrial tachycardia. A repeat ECG was obtained after a mean follow-up of 8+/-3 years in asymptomatic subjects and 7+/-3 years in symptomatic patients. After the follow-up, seven (26%) out of 27 patients were still in a similar ectopic atrial rhythm, 10 (37%) showed a change in P wave morphology and 10 (37%) were in sinus rhythm. Heart rate was significantly slower (mean rate 81+/-19 vs 109+/-17 beats. min-1) in the repeat ECGs. CONCLUSION: Asymptomatic ectopic atrial tachycardia is not an uncommon finding in a population of young males. The majority of patients show slowing of heart rate in the course of time, either with restoration of sinus rhythm or with a change in P wave morphology, suggesting that the ectopic foci undergo gradual degeneration with time.

QT interval and arrhythmic risk assessment after myocardial infarction.

To assess ventricular repolarization features as predictors of ventricular tachyarrhythmias (VT) in patients with previous myocardial infarction, we performed a dynamic study of QT interval from 24-hour electrocardiographic data. QT rate dependence was enhanced in patients with VT when compared with patients without VT.

Dosimetric verification of the dynamic intensity-modulated radiation therapy of 92 patients.

PURPOSE: To verify that optimized dose distributions provided by an intensity-modulated radiation therapy (IMRT) system are delivered accurately to human patients. METHODS AND MATERIALS: Anthropomorphic phantoms are used to measure IMRT doses. Four types of verification are developed for: I) system commissioning with beams optimized to irradiate simulated targets in phantoms, II) plans with patient-optimized beams directed to phantoms simulating the patient, III) patient-phantom hybrid plans with patient-optimized beams calculated in phantom without further optimization, and IV) in vivo measurements. Phantoms containing dosimeters are irradiated with patient-optimized beams. Films are scanned and data were analyzed with software. Percent difference between verified and planned maximum target doses is defined as "dose discrepancy" (deltavp). The frequency distribution of type II deltavp from 204 verification films of 92 IMRT patients is fit to a Gaussian. Measurements made in vivo yield discrepancies specified as deltaivp, also fit to a Gaussian. RESULTS AND DISCUSSION: Verification methods revealed three systematic errors in plans that were corrected prior to treatment. Values of [deltavp] for verification type I are <2%. Type II verification discrepancies are characterized by a Gaussian fit with a peak 0.2% from the centroid, and 158 [deltavp] <5%. The 46 values of [deltavp] >5% arise from differences between phantom and patient geometry, and from simulation, calculation, and other errors. Values of [deltavp] for verification III are less than half of the values of [deltavp] for verification II. A Gaussian fit of deltaivp from verification IV shows more discrepancy than the fit of deltavp, attributed to dose gradients in detectors, and exacerbated by immobilization uncertainty. CONCLUSIONS: Dosimetric verification is a critical step in the quality assurance (QA) of IMRT. Hybrid Verification III is suggested as a preliminary quality standard for IMRT.

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Abnormalities in beat-to-beat dynamics of heart rate before the spontaneous onset of life-threatening ventricular tachyarrhythmias in patients with prior myocardial infarction.

BACKGROUND: Beat-to-beat analysis of RR intervals can reveal patterns of heart-rate dynamics, which are not easily detected by summary measures of heart-rate variability. This study was designed to test the hypothesis that alterations in RR-interval dynamics occur before the spontaneous onset of ventricular tachyarrhythmias (VT). METHODS AND RESULTS: Ambulatory ECG recordings from 15 patients with prior myocardial infarction (MI) who had spontaneous episodes of sustained VT during the recording and VT inducible by programmed electrical stimulation (VT group) were analyzed by plotting each RR interval of a sinus beat as a function of the previous one (Poincaré plot). Poincaré plots were also generated for 30 post-MI patients who had no history of spontaneous VT events and no inducible VT (MI control subjects) and for 30 age-matched subjects without heart disease (normal control subjects). The MI control subjects and VT group were matched with respect to age and severity of underlying heart disease. All the healthy subjects and MI control subjects showed fan-shaped Poincaré plots characterized by an increased next-interval difference for long RR intervals relative to short ones. All the VT patients had abnormal plots: 9 with a complex pattern, 3 ball-shaped, and 3 torpedo-shaped. Quantitative analysis of the Poincare plots showed the SD of the long-term RR-interval variability (SD2) to be smaller in all VT patients (52+/-14 ms; range, 31 to 75 ms) than in MI control subjects (110+/-24 ms; range, 78 to 179 ms, P<.001) or the normal control subjects (123+/-38 ms, P<.001), but the SD of the instantaneous beat-to-beat variability (SD1) did not differ between the groups. The complex plots were caused by periods of alternating sinus intervals, resulting in an increased SD1/SD2 ratio in the VT group. This ratio increased during the 1-hour preceding the onset of 27 spontaneous VT episodes (0.43+/-0.20) compared with the 24-hour average ratio (0.33+/-0.19) (P<.01). CONCLUSIONS: Reduced long-term RR-interval variability, associated with episodes of beta-to-beat sinus alternans, is a highly specific sign of a propensity for spontaneous onset of VT, suggesting that abnormal beat-to-beat heart-rate dynamics may reflect a transient electrical instability favoring the onset of VT in patients conditioned by structurally abnormal hearts.

No difference in cardiac innervation of diabetic patients with painful and asymptomatic coronary artery disease.

OBJECTIVE: To test the hypothesis that diabetic autonomic neuropathy interfering with sensory impulses from the heart by sympathetic denervation is the major cause of the high prevalence of asymptomatic coronary artery disease (CAD) in diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated cardiac sympathetic innervation in a population-based group of 10 asymptomatic diabetic patients with angiographically proven CAD and in an age- and sex-matched group of 10 diabetic patients with symptomatic CAD using [123I]metaiodobenzylguanide (MIBG) scintigraphy. Exercise electrocardiography and myocardial perfusion imaging by 201Tl were used to detect myocardial ischemia, and standard cardiovascular tests were used to diagnose autonomic nervous dysfunction. RESULTS: Thallium scintigraphy revealed perfusion defects in all 10 symptomatic patients and in 9 of the asymptomatic patients. MIBG accumulation defects were found in all cases with painless and with painful disease. In the asymptomatic group, the denervation area exceeded the ischemic area in six cases and areas with total MIBG accumulation defects were seen in four cases. In one case, the MIBG defect was not in the ischemic region. In the symptomatic group, the denervation area exceeded the area of the ischemic region in all cases and areas of total denervation were seen in six cases. The autonomic nervous function tests were abnormal in two asymptomatic and three symptomatic patients with CAD. CONCLUSIONS: Cardiac sympathetic denervation is common in both patients with painful CAD and patients with asymptomatic CAD regardless of diabetic autonomic neuropathy. This finding supports the view that sympathetic innervation of the heart is highly sensitive to ischemia and this profound effect of ischemia masks the potential effects of autonomic neuropathy on sympathetic innervation. Mechanisms leading to the lack of ischemic pain in diabetic patients with CAD are complex and are not solely explained by autonomic neuropathy.

Significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with previous myocardial infarction.

OBJECTIVE: To study the significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with a remote myocardial infarction. SETTING: Tertiary referral cardiac centre. METHODS: Angiographic filling of the infarct related artery was assessed in a consecutive series of 85 patients with different susceptibilities to ventricular tachyarrhythmias after previous (> 3 months) Q wave myocardial infarction: 30 patients had a history of cardiac arrest (n = 16) or sustained ventricular tachycardia (n = 14), and sustained ventricular tachyarrhythmia was inducible in these by programmed electrical stimulation (arrhythmia group); 47 patients had no clinical arrhythmic events and no inducible ventricular tachyarrhythmias during programmed ventricular stimulation (control group). Eight patients without a history of any arrhythmic events were inducible into ventricular tachycardia. RESULTS: The patients in the arrhythmia group were older (63 (SD 8) years) than the control patients (59 (6) years, P < 0.05), and had larger left ventricular volumes in cineangiography (P < 0.01), but ejection fraction, severity of left ventricular wall motion abnormalities, previous thrombolytic therapy, and time from previous infarction did not differ between the groups. Patients with susceptibility to ventricular tachyarrhythmias more often had a totally occluded infarct related artery on angiography (77%) than patients without arrhythmia susceptibility (21%) (P < 0.001), and complete collateral filling of the infarct artery in cases without complete anterograde filling was less common in the arrhythmia group than in the control group (P < 0.001). Patients without a history of malignant arrhythmia but with inducible ventricular tachyarrhythmia also had no or poor perfusion of the infarct artery more often than the patients without inducible arrhythmia (P < 0.001). Logistic multiple regression showed that no or poor anterograde or collateral filling of the infarct related artery was the most powerful predictor of susceptibility to ventricular tachyarrhythmias (P < 0.001). Left ventricular size and function were not independently related to arrhythmic susceptibility. CONCLUSIONS: No or poor angiographic filling of the infarct related artery is closely associated with susceptibility to ventricular tachyarrhythmias late after acute myocardial infarction, suggesting that perfusion of the infarct artery will modify favourably the electrophysiological substrate of the infarct scar independently of the myocardial salvage achieved by early reperfusion.

Effects of perfusion of the infarct-related artery on risk markers of life-threatening arrhytmias in patients with prior myocardial infarction

Programmed electrical stimulation (PES), angiographic studies, Holter recording, 12-lead ECG and signal averaged ECG (SAECG, n=63) were performed in 109 consecutive patients with a prior Q-wave myocardial infarction (MI). Sixty-five patients (59 por cento) had TMI-class ) or 1 antegrade perfusion without significant collateral filling of the infarct related artery (IRA) (=poor persuion) and forty four (41 por cento) had either good antegrade or collateral perfusion of the IRA. The severity of corony artery disease or ejection fraction did not differ between the patients with poor or good perfusion of IRA. Heart rate variability and presence of late potentials on SAECG were also similar between the groups. but the dispersion of the QT interval was prolonged in the patients with poor perfusion of IRA (86 +/- 35 ms vs. 69 +/- 27 ms, p<0.01). The patients with poor perfusion of IRA had more often a clinical history of VT compared to those with good perfusion (68 por cento vs 9 por cento, p<0.01). Patets with good filling of the IRA after a prior MI have a low risk for VT, suggesting that preserved perfusion of the infarct scar stabilizes the electrophysiologic substrate.

Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction.

OBJECTIVES: The aim of this study was to estimate the value of QT dispersion measurement from the standard 12-lead electrocardiogram (ECG) in identifying patients susceptible to reentrant ventricular tachyarrhythmias after a previous myocardial infarction. BACKGROUND: Variability in QT interval duration on the different leads of the 12-lead ECG has been proposed as an indicator of risk for ventricular arrhythmias in different clinical settings, but the value of QT dispersion measurement in identifying patients at risk for reentrant ventricular tachyarrhythmias after myocardial infarction is not known. METHODS: The QT interval duration, QT dispersion and clinical and angiographic variables were compared between 30 healthy subjects; 40 patients with a previous myocardial infarction but no history of arrhythmic events or inducible ventricular tachycardia during programmed electrical stimulation; and 30 postinfarction patients with a history of cardiac arrest (n = 12) or sustained ventricular tachycardia (n = 18) and inducible, sustained monomorphic ventricular tachycardia by electrical stimulation. RESULTS: Dispersion of the corrected QT interval (QTc) differed significantly between the study groups and was significantly increased in patients with susceptibility to ventricular tachyarrhythmias ([mean +/- SD] 104 +/- 41 ms) compared with that in both healthy subjects (38 +/- 14 ms, p < 0.001) and postinfarction patients with no susceptibility to arrhythmias (65 +/- 31 ms, p < 0.001). Maximal QT interval duration was also prolonged in the group with arrhythmias compared with that in the other groups (p < 0.001). Multivariate analysis, including clinical and angiographic variables, QT dispersion and maximal QT interval, showed that QT dispersion was the independent factor that most effectively identified the patient groups with and without susceptibility to ventricular tachyarrhythmias (p < 0.001). CONCLUSIONS: Increased QT dispersion is related to susceptibility to reentrant ventricular tachyarrhythmias, independent of degree of left ventricular dysfunction or clinical characteristics of the patient, suggesting that the simple, noninvasive measurement of this interval from a standard 12-lead ECG makes a significant contribution to identifying patients at risk for life-threatening arrhythmias after a previous myocardial infarction.

Impaired low-frequency oscillations of heart rate in patients with prior acute myocardial infarction and life-threatening arrhythmias.

Myocardial infarction results in abnormal cardiac autonomic function, which carries an increased risk of cardiac mortality, but it is not well known whether autonomic dysfunction itself predisposes patients to life-threatening arrhythmias or whether it merely reflects the severity of underlying ischemic heart disease. To determine the significance of abnormalities of cardiovascular neural regulation on the risk for ventricular tachycardia (VT), heart rate (HR) variability in the time and frequency domain were compared in a case-control study between 30 patients with a prior myocardial infarction and a history of sustained VT (n = 18) or cardiac arrest (n = 12) (VT group) and 30 patients with a prior myocardial infarction but no arrhythmic events (control group). The patient groups were carefully matched with respect to age, sex, location, ejection fraction, number of prior infarctions, number of diseased coronary arteries, and beta-blocking medication. In all patients in the VT group, inducibility into sustained VT was achieved, but none of the control patients had inducible nonsustained or sustained VT during programmed electrical stimulation. Patients in the VT group had a significantly lower SD of the RR intervals (p < 0.01), and reduced ultra low-, very low-, and low-frequency power spectral components of HR variability (p < 0.001 for all) than controls, but the high-frequency component of HR variability did not differ significantly between groups. In multiple regression analysis, reduced very low-frequency power of HR variability was the strongest independent predictor of VT susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to determine the relation between autonomic control of heart rate and the spontaneous occurrence and inducibility of ventricular arrhythmias in patients with coronary artery disease. BACKGROUND: Low heart rate variability increases the risk of arrhythmic events. It is not known whether impaired autonomic heart rate control reflects alterations in functional factors that contribute to the initiation of spontaneous arrhythmias or whether it is the consequence of an anatomic substrate for reentrant tachyarrhythmias. METHODS: Fifty-four patients with coronary artery disease with a history of sustained ventricular tachycardia (n = 25) or cardiac arrest (n = 29) were studied by 24-h ambulatory electrocardiographic recording and by programmed electrical stimulation. Heart rate variability was compared among the patients with and without spontaneous ventricular arrhythmias and with and without inducibility of sustained ventricular tachyarrhythmias. RESULTS: Eight patients had a total of 21 episodes of sustained ventricular tachycardia on Holter recordings. Standard deviation of RR intervals and low frequency and very low frequency components of heart rate variability were significantly blunted in patients with sustained ventricular tachycardias compared with those without repetitive ventricular ectopic activity (p < 0.05, p < 0.01 and p < 0.05, respectively). However, no significant alterations were observed in heart rate variability before the onset of 21 episodes of sustained ventricular tachycardia. Heart rate variability did not differ between the patients with or without nonsustained episodes of ventricular tachycardia. In patients with frequent ventricular ectopic activity, low frequency and very low frequency power components were significantly blunted compared with those with infrequent ventricular ectopic activity (p < 0.01 and p < 0.001, respectively). Heart rate variability did not differ significantly between the patients with and without inducible sustained ventricular tachyarrhythmias. CONCLUSIONS: Impaired very low and low frequency oscillation of heart rate reflects susceptibility to the spontaneous occurrence of ventricular arrhythmias but may not reflect the instantaneous triggers for life-threatening arrhythmias or a specific marker of the arrhythmic substrate for ventricular tachyarrhythmias.

Asymptomatic coronary artery disease in diabetes: relation to common risk factors, lipoproteins, apoproteins and apo E polymorphism.

The risk factors for asymptomatic coronary artery disease (CAD) were examined in 138 diabetic patients. Following non-invasive screening examinations (exercise electrocardiography, dynamic thallium scintigraphy, 24-h electrocardiographic recording), CAD was confirmed angiographically in 21 symptom-free diabetic subjects with an ischaemic finding in at least one of the non-invasive tests. The prevalence of asymptomatic CAD in this cohort of diabetic patients was 21/132 (16%), which may be an underestimation because 6 patients refused angiography. Risk factors (age, diabetes, smoking, hypertension, serum lipoproteins, apoproteins and apo E phenotypes) were analysed according to the presence or absence of CAD. Multivariate logistic stepwise analysis did not show any definite changes of serum lipids, lipoproteins and apoproteins in type 1 (n = 72) and type 2 (n = 66) diabetic patients with or without asymptomatic CAD. The only factors associated with asymptomatic CAD were the duration of diabetes (P < 0.005) and the age of the patient (P < 0.05). These results suggest that in diabetic patients the major risk factor for premature coronary atherosclerosis is diabetes itself. Assessment of other risk factors does not seem to define any subgroup with asymptomatic CAD.