Retinal micro-vascular and aortic macro-vascular changes in postmenopausal women with primary hyperparathyroidism.

Aim of the study was to evaluate the micro and macro-vascular changes in patients with primary hyperparathyroidism (PHPT) compared to controls. 30 postmenopausal PHPT women (15 hypertensive and 15 normotensive) and 30 normotensive controls underwent biochemical evaluation of mineral metabolism and measurements of arterial stiffness by 24 hour ambulatory blood pressure monitoring. Retinal microcirculation was imaged by a Retinal Vessel Analyzer. PHPT patients also underwent bone mineral density measurements and kidney ultrasound. PHPT patients had higher mean calcium and parathyroid hormone values compared to controls. Evaluating macro-vascular compartment, we found higher values of 24 hours-systolic, diastolic blood pressure, aortic pulse wave velocity (aPWV) and aortic augmentation index (Aix) in hypertensive PHPT, but not in normotensive PHPT compared to controls. The eye examination showed narrowing arterial and venular diameters of retinal vessels in both hypertensive and normotensive PHPT compared to controls. In hypertensive PHPT, 24 hours systolic blood pressure was associated only with parathyroid hormone (PTH) levels (beta = 0.36, p = 0.04). aPWV was associated with retinal diameter (beta = -0.69, p = 0.003), but not with PTH. Retinal artery diameter was associated with PTH (beta = -0.6, p = 0.008). In the normotensive PHPT, only PTH was associated with retinal artery diameter (beta = -0.60, p = 0.01) and aortic AIx (beta = 0.65, p = 0.02). In conclusion, we found macro-vascular impairment in PHPT and that micro-vascular impairment is negatively associated with PTH, regardless of hypertension in PHPT.

Reduction of arrhythmias in primary hyperparathyroidism, by parathyroidectomy, evaluated with 24-h ECG monitoring.

OBJECTIVE: Hypercalcemia may induce arrhythmias. There are no data on the prevalence of arrhythmias in primary hyperparathyroidism (PHPT) in daily life. Aim of the study was to investigate both the prevalence of arrhythmias in patients with PHPT compared to controls and the impact of parathyroidectomy, evaluated by 24-h electrocardiogram (ECG) monitoring. DESIGN: This is a randomized study. METHODS: Twenty-six postmenopausal women with PHPT and 26 controls were enrolled. PHPT patients were randomized to two groups: 13 underwent parathyroidectomy (Group A) and 13 were followed up conservatively (Group B). After 6 months, patients were studied again. Each patient underwent mineral metabolism biochemical evaluation, bone mineral density measurement, standard ECG and 24-h ECG monitoring. RESULTS: PHPT patients showed higher calcium and parathyroid hormone compared to controls and a higher prevalence of both supraventricular (SVBPs) and ventricular premature beats (VPBs) during 24-h ECG monitoring. Groups A and B showed no differences in mean baseline biochemical values and ECG parameters. Mean value of QTc in PHPT groups was in the normal range at baseline, but significantly shorter than controls. A negative correlation was found between QTc and ionized calcium levels (r = -0.48, P < 0.05). After parathyroidectomy, Group A had a significant reduction in SVPBs and VPBs compared to baseline and restored normal QTc. Group B showed no significant changes after a 6-month period. CONCLUSIONS: The increased prevalence of SVPBs and VPBs is significantly reduced by parathyroidectomy, and it is mainly related to the short QTc caused by hypercalcemia.

Comparisons of microvascular and macrovascular changes in aldosteronism-related hypertension and essential hypertension.

Case-control observational study to evaluate the microvascular and macrovascular changes in patients with hypertension secondary to primary aldosteronism (PA), essential hypertension (EH) and healthy subjects. Measurements of arterial stiffness including augmentation index (AIx) and pulse wave velocity (PWV) were assessed using a TensioClinic arteriograph system. Retinal microcirculation was imaged by a Retinal Vessel Analyzer (RVA) and a non-midriatic camera (Topcon-TRC-NV2000). IMEDOS software analyzed the retinal artery diameter (RAD), retinal vein diameters (RVD) and arteriole-to-venule ratio (AVR) of the vessels coming off the optic disc. Thirty, 39 and 35 patients were included in the PA, EH and control group, respectively. The PA group showed higher PWV values compared only with the control group. The mean brachial and aortic AIx values did not show significant difference between groups. In the PA group, the mean RVD and AVR values were significantly lower than in the EH and control groups, whereas the parameters did not differ between the EH and control groups. In conclusion, AVR appears significantly modified in the PA group compared with the EH group and could represent an early and more reliable indicator of microvascular remodeling.

Acute effect of zoledronic acid on the risk of cardiac dysrhythmias.

There have been recent concerns regarding the risk of serious adverse events, such as cardiac dysrhythmia and atrial fibrillation (AF), associated with bisphosphonate use in osteoporosis. This open-label, non-randomized, crossover pilot study evaluated short-term effects of zoledronic acid and placebo on the occurrence of cardiac dysrhythmias and prodysrhythmic profile in postmenopausal women with osteoporosis and low risk of cardiac dysrhythmias. Fifteen postmenopausal women (mean age 70.7 ± 6.9 years) with osteoporosis received placebo infusion on day 1 and zoledronic acid 5 mg on day 7. Standard 12-lead resting EKG measured QT parameters at baseline and up to 24 h after infusion. Continuous 24-h EKG assessed dysrhythmic events and heart rate variability (HRV) for 24 h after infusion. There were no statistically significant differences in resting EKG parameters between placebo and zoledronic acid: QTc (404.28 ± 9.28 and 410.63 ± 18.43 ms), no significant differences in mean serum electrolytes at baseline and after infusion, and no significant association between QT/QTc parameters and serum electrolytes before and after each infusion (QTc: 401.83 ± 17.73 for zoledronic acid and 404.65 ± 16.79 for placebo). There was no significant difference in HRV parameters between placebo and zoledronic acid, and no dysrhythmias were recorded at rest or with 24 h EKG monitoring. Zoledronic acid does not produce dysrhythmia or prodysrhythmic effects in the short term. Among possible mechanisms proposed for cardiac dysrhythmias with zoledronic acid, no serum electrolyte or autonomous nervous system balance perturbations have been reported.

Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associating with pain, fatigue and other secondary aspects. Though not considered a diagnostic criterion for most EDS subtypes, cardiovascular involvement is a well-known complication in EDS. A case-control study was carried out on 28 adults with JHS/EDS-HT diagnosed according to current criteria, compared to 29 healthy subjects evaluating resting electrocardiographic (ECG), 24-h ECG and resting heart ultrasound data. Results obtained in the ECG studies showed a moderate excess in duration of the PR interval and P wave, an excess of heart conduction and rate abnormalities and an increased rate of mitral and tricuspid valve insufficiency often complicating with "true" mitral valve prolapse in the ecocardiographic study. These variable ECG subclinical anomalies reported in our sample may represent the resting surrogate of such a subnormal cardiovascular response to postural changes that are known to be present in patients with JHS/EDS-HT. Our findings indicate the usefulness of a full cardiologic evaluation of adults with JHS/EDS-HT for the correct management.

Electrical and Myocardial Remodeling in Primary Aldosteronism.

OBJECTIVE AND DESIGN: Primary aldosteronism (PA) represents the most common cause of secondary hypertension. A higher risk of cardiovascular events has been reported in patients with PA than in otherwise similar patients with essential hypertension (EH). So far, only a few studies investigated the electrocardiographic changes in PA patients compared to EH patients. METHODS: To investigate the electrocardiographic changes and heart remodeling in PA, we enrolled 61 consecutive patients, 30 with PA [12 with aldosterone-producing adrenal cortical adenoma (APA) and 18 with bilateral adrenal hyperplasia-idiopathic adrenal hyperplasia] and 30 with EH. In all subjects, electrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram. RESULTS: No significant differences in age, sex, body mass index, and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patients with PA respect to EH (p < 0.003 and <0.002, respectively). A first degree atrio-ventricular block was present in 16% of the patients with PA and only in 3.2% of those with EH. In PA patients, the interventricular septum thickness (IVST) correlated with PR duration (r = 0.51; p < 0.03). Left ventricular hypertrophy was present in 53% of the patients with PA and in 26% of the patients with EH (χ(2), p < 0.03). CONCLUSION: In this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.

Lack of the QTc physiologic decrease during cardiac stress test in patients with type 2 diabetes treated with secretagogues.

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test.

Progressive loss in circulating volume during haemodialysis can be monitored by time voltage integral area of QRS complex: pilot study.

INTRODUCTION: Time voltage area of QRS is a parameter that showed a close association with modifications in endoventricular volume. The aim of the study was to investigate the efficacy of this parameter in identifying progressive reduction in circulating blood volume (BV) during haemodialytic treatment (HT). MATERIAL AND METHODS: Thirteen uraemic patients were studied. XYX like leads were monitored before, during and after HT. Summation of areas of each QRS complex was named QRS total area (TA). RESULTS: Increase in QRS TA and decrease in BV were found after vs. before HT. Progressive increase in QRS TA is strongly linked to a progressive reduction of BV during HT. CONCLUSIONS: THESE FINDINGS ENCOURAGE USE OF ECG MONITORING DURING HT WITH A DUAL PURPOSE: rhythm and haemodynamic control. In fact, excessive or insufficient subtractions of water, with consequent hypotensive or cardiorespiratory crisis, are the most frequent complications in these patients.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test.

OBJECTIVE: To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). METHODS: Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. RESULTS: Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. CONCLUSIONS: PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Arrhythmias in primary hyperparathyroidism evaluated by exercise test.

BACKGROUND: Hypercalcemia induces arrhythmias and shortening of QT. The aim of this study was to investigate risk factors for occurrence of arrhythmias in patients with primary hyperparathyroidism (PHPT) during bicycle ergometer exercise test (ET). METHODS: Thirty PHPT postmenopausal women (mean age, 60·9 ± 8·0 years) and 30, sex and age-matched, controls underwent ET, echocardiogram and mineral metabolism biochemical evaluation. The following stages were considered during ET: rest, peak exercise, recovery (early recovery, 2 and 10 min after peak exercise). QT was corrected with Bazett's formula (QTc). RESULTS: Compared with controls, PHPT patients showed an increased occurrence of ventricular premature beats (VPBs) during ET (26·6% vs. 6·6%, P = 0·03). Being affected by PHPT predicted the onset of VPBs at peak exercise (P = 0·04) and recovery (P = 0·03), as shown by logistic regression analysis. In PHPT patients, serum calcium level was a predictor of VPBs at peak exercise (P = 0·05). QTc in patients with PHPT was in the normal range. Serum calcium level showed a negative correlation with QTc (P = 0·01) in whole sample. Compared with controls, PHTP patients had QTc significantly shorter for every stage of ET, except at peak exercise. Physiological reduction of QTc interval from rest to peak exercise was not seen in patients with PHPT, QTc at rest being the only predictor of QTc in every stage, as shown by multivariate regression analysis. CONCLUSIONS: In patients with PHPT, an increased occurrence of VPBs and a different QTc adaptation during ET were observed and may represent risk factors for major arrhythmias.

Dopamine receptor subtypes in the human coronary vessels of healthy subjects.

OBJECTIVE: Dopamine D(1)-D(5) receptors subtypes were studied in human coronary vessels of healthy subjects to assess their localization and their expression. METHODS: Samples of intraparenchymal and extraparenchymal branches of human coronary arteries and veins were harvested from four normal native hearts explanted from four young brain dead heart donors in case of orthoptic transplant, not carried out for technical reasons. In all the samples morphological, biochemical, immunochemical, and morphometrical studies were performed including quantitative analysis of images and evaluation of data. RESULTS: Microanatomical section showed healthy coronary vessels, which expressed all dopamine receptors (from D(1) to D(5)) with a different pattern of distribution between the different layers, in the intra and in the extraparenchymal branches.D(1) and D(5) (with a prevalence D(1) over D(5)) were distributed in the adventitia and to a lesser extent in the outer media but they were absent in arterioles, capillaries and venules. Endothelial and the middle layer showed D(2), D(3) and D(4) receptors, with a greater expression of D(2). Immunoblot analysis of dopamine monoclonal antibodies and dopamine receptors showed a different migration band for each receptor: D(1) (45 KDa); D(2) (43 KDa); D(3) (42 kDa); D(4) (40-42 KDa); D(5) (38-40 KDa) CONCLUSION: These findings demonstrate the presence of all dopamine receptor subtypes in the wall of human coronary vessels of healthy subjects. Dopamine D(1) and D(2) receptor subtypes are the most expressed, suggesting their prominent role in the coronary vasoactivity.

A study on QT interval in patients affected with inflammatory bowel disease without cardiac involvement.

Cardiac involvement has been studied quite extensively in patients affected by inflammatory bowel disease but, as of now, there is no data regarding QT alterations which are well known to be linked to the risk of dangerous arrhythmias. In this study, QT parameters were digitally measured on standard 12-lead ECG in a population of 20 patients affected by inflammatory bowel disease (IBD), with no prior (recent or old) history of cardiac disease and no evidence of electrolyte imbalance. Eighteen healthy subjects formed the control group. The results obtained using non-parametric statistics (Wilcoxon-Mann-Whitney test) showed that heart rate corrected QT interval (QTc) and QTc dispersion (QTc d) values were both significantly higher in IBD patients than in the control group. QTc rank sum values in patients affected by inflammatory bowel disease were 469 versus 311 in healthy subjects (Z = 1.939, p = 0.0263). QTc d rank sum values were 460 in IBD patients versus 320 in controls (Z = 1.686 with p = 0.0459). Regardless of the cause of these QT alterations, it appears evident that accurate monitoring of QT parameters is required in these patients who often experience electrolyte disturbances and who may, in some cases, be undergoing treatment with potentially cardiotoxic drugs such as infliximab.

Analysis of extrema of heartbeat time series in exercise test.

The heartbeat time series of the electrocardiogram recorded during exercise test clearly reflects the physiological control mechanism of the autonomic nervous system on heart rate. This series shows both decreasing and increasing trends and variability of the variance. We analyse the series of intervals between two consecutive extrema, i.e. the durations of accelerations or decelerations of heart rate. We compute the distribution of the length of these intervals and their mean in a model of stationary independent variables, where they are independent of the variables' distribution. We use the mean length as discriminant statistics to compare stress and recovery phases. Data analysis performed over the heartbeat series of 14 healthy subjects shows significant difference between stress and recovery.

The loss of entropy circadian rhythm in sinusal R-R intervals of type 1 diabetic pregnant women suggests an indeterministic chaos in cardiac pacing (minimum delirium cordis syndrome). A newly identifiable type of silent cardiac dysautonomia?

OBJECTIVE: The scope of this study is to detect whether or not the entropy (E) circadian rhythm (CR) is maintained preserved in sinusal R-R intervals (SRRI), its loss being the expression of a transition to an indeterministic chaos in heart rate variability (HRV). METHODS: The E of SRRI was estimated in 14 type I diabetic pregnant women (DPW) in the first trimester of an apparently uncomplicated gestation (7 patients - mean age = 30.3 +/- 4.1 y - without clinical and laboratory evidence of cardiac autonomic neuropathy, and 7 patients - mean age = 30.7 +/- 3.6 y - with positive tests for a cardiac dysautonomia). The E CR was studied via the single cosinor method, and summarized via the population-mean cosinor method. RESULTS: The E CR was found not to be preserved in both the investigated type I DPW, despite the occurrence of the SRRI CR. CONCLUSIONS: The loss of the E CR confirms that in type I DPW there is a transition to an indeterministic disorder in HRV due to the lack of an autocorrelated periodic chaos in cardiac pacing. Such an unphysiological neurovegetative regulation suggests a new silent cardiac dysautonomic syndrome, that we intend to call "minimum delirium cordis syndrome" (MDCS). Can the MDCS be regarded as a condition of cardiovascular risk? To answer this question, it seems justified to suggest that the study of the E CR should be added to the routine tests that are presently applied to clinical analysis of the Holter ECG, being the classic tests of linear analysis not methodologically suitable for detecting the indeterministic chaos of the MDCS.

Increased risk of cardiac death in primary hyperparathyroidism: what is a role of electrical instability?

BACKGROUND: Increased risk of death in patients with primary hyperparathyroidism (PHPT) is referred to cardiovascular complications induced by hypercalcemia. At the moment the role of bioelectrical risk and of enhanced sympathetic activity, not related to cardiovascular complications, is unknown in PHPT patients. METHODS: The study was designed to evaluate the QT parameters and sympathovagal balance in 28 PHPT uncomplicated patients compared to 29 healthy subjects (HS). Nine of 28 patients were restudied after parathyroidectomy. Standard ECG, short and 24-h ECG monitoring were performed to calculate QT parameters and Heart Rate Variability (HRV). RESULTS: QTc interval resulted shorter in PHPT patients than in HS and QTc dispersion resulted higher in PHPT patients than HS. The physiological adaptation of QT length to R-R interval was lacking in PHPT patients. Enhanced sympathetic tone was found in PTHP patients than controls. These data were confirmed after parathyroidectomy. CONCLUSION: Our findings revealed an increased risk to develop life-threatening arrhythmias in PHPT patients due to bioelectrical instability induced by hypercalcemia. Parathyroidectomy doesn't seem to reverse this abnormality.

Effect of acute hyperinsulinemia on ventricular repolarization in uncomplicated obesity.

BACKGROUND: Acute hyperinsulinemia has been shown to increase QTc interval in lean subjects, but data on obese subjects are still unclear. Aim of this study was to evaluate the effect of acute hyperinsulinemia on QTc interval and QTc dispersion in uncomplicated obesity. METHODS: We calculated QTc duration and QTc dispersion in 30 uncomplicated obese subjects (mean age 32.2 +/- 7, BMI 36.7 +/- 9.4 kg/m(2)) by measurements of 12-lead ECG recording during a euglycemic hyperinsulinemic clamp. RESULTS: Insulin infusion during the clamp did not significantly modify QTc interval and QTc dispersion in uncomplicated obese subjects (401.5 +/- 29.2 vs. 413.7 +/- 30.5; 35.4 +/- 10.5 vs. 38.7 +/- 14.5, respectively). CONCLUSIONS: Acute hyperinsulinemia seems to no significantly affect ventricular repolarization in uncomplicated obesity. Insulin resistance and the absence of diabetes and hypertension could explain, at least in part, this finding.