Hypertension is associated with narrower retinal arteriolar calibre in persons with and without coronary artery disease.

The aims of this study were to investigate independent associations between hypertension and retinal vessel calibre in a high cardiovascular risk cohort and to determine whether these associations also exist in patients without coronary artery disease (CAD). The Australian Heart Eye Study is an observational study that surveyed 1680 participants presenting to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Hypertension was defined as systolic >140 mm Hg, diastolic >90 mm Hg or treated (use of antihypertensive medications). Retinal arteriolar and venular calibres were measured from retinal photographs. CAD was quantified using severity (Gensini) and extent scores. Subanalyses were performed for people with and without CAD and for men and women. A total of 1114 participants had complete data on hypertension, coronary vessel evaluation and retinal vessel measurements and were included in cross-sectional analyses. Among persons with CAD, those with hypertension (compared with without) had narrower retinal arteriolar calibre (mean arteriolar calibre difference 2.1 µm, P=0.02), adjusting for age, sex, ethnicity, body mass index, smoking status and fellow vessel calibre. This association was also present among persons without CAD (mean difference 5.0 µm, P=0.04). Stratification by sex indicated that women with hypertension had marginally narrower retinal arterioles compared with normotensive women (multivariable-adjusted P=0.04). No significant association between hypertension and retinal arteriolar calibre was observed in men (P=0.13). No significant differences in retinal venular calibre were observed (P>0.05). In conclusion, in both subjects with and without CAD, hypertension was independently associated with narrower retinal arterioles.

Mammary artery to saphenous vein composite T grafts for coronary artery bypass: late follow-up.

AIM: Composite arterial grafts using a T configuration from the left internal mammary artery (LIMA) are commonly used for coronary artery surgery. Little data exist regarding the use of saphenous vein (SV) in composite grafts from the LIMA. This study aimed to determine whether LIMA patency was reduced by the attachment of a SV T graft. METHODS: Patients (N.=166) who underwent coronary bypass surgery using the LIMA for SV graft inflow were identified from a database. Post discharge angiography was performed for investigation of symptoms or evidence of myocardial ischemia. Follow-up identified episodes of angiography, re-intervention and death. RESULTS: Complete follow-up was obtained in 165 patients, mean 6 years (0-16 years). The mean patient age was 70 years and 43 patients underwent concomitant procedures. In 25 patients who underwent post discharge angiography, the LIMA and T anastomoses were widely patent in 14 patients. The SV graft was occluded at the T anastomosis in 8 patients and the distal limb of the LIMA was occluded in 2 patients. In no patients were the vein and LIMA both occluded. CONCLUSION: The use of the LIMA for SV graft inflow does not appear to compromise the LIMA graft even when SV graft occlusion occurs.

Optimisation of coronary angiography exposures requires a multifactorial approach and careful procedural definition.

OBJECTIVE: This study investigates the factors associated with higher doses for both single-plane and biplane procedures and establishes centre-specific 75th percentile levels. METHODS: 602 patients undergoing coronary angiography in a large hospital at Sydney were recruited to the study, and causal agents for high radiation doses were investigated: gender, procedural complexity, severity of coronary artery disease, presence of coronary bypass grafts, entry approach (radial or femoral), level of operator experience; and a single-plane or a biplane imaging system was employed. RESULTS: The 75th percentile levels were calculated. The results demonstrated that, for both systems, higher exposures were associated with patients who were male (p<0.001), had coronary vessel disease (p<0.001) and had a history of coronary bypass grafts (p<0.001). In addition, for biplane systems, procedural complexity (p<0.001), types of entry approach (p<0.001) and levels of operator experience (p<0.001) significantly impacted upon the dose. Biplane examinations recorded higher doses than single-plane procedures (p<0.001) and the inclusion of left-sided ventriculography contributed to the overall dose by up to 10%. CONCLUSION: The 75th percentile levels in this study represent the tentative reference levels and are 48.9, 44.2 and 56 Gy cm(2) for all exposures, single-plane- and biplane-specific exposures, respectively, and compare favourably with the diagnostic reference level values established elsewhere internationally, with only the UK and Irish data being lower. ADVANCES IN KNOWLEDGE: Specific agents have been identified for dose-reducing strategies and the importance of operator training is highlighted. The assumption that biplane procedures may reduce the patient dose should be treated with caution.

Randomized double-blind trial of sotalol versus lignocaine in out-of-hospital refractory cardiac arrest due to ventricular tachyarrhythmia.

AIM: We aimed to compare the efficacy of sotalol versus lignocaine for the treatment of patients with out-of-hospital ventricular fibrillation refractory to > or = 4 defibrillatory shocks. BACKGROUND: The outcome of patients in ventricular fibrillation refractory to > or = 4 defibrillatory shocks is poor. In a previous randomized trial, sotalol was superior to lignocaine for acute termination of ventricular tachycardia not causing loss of consciousness. METHODS: Patients of the Ambulance Service of New South Wales treated by paramedics with continued ventricular fibrillation despite standard resuscitation and > or = 4 defibrillatory monophasic shocks were eligible. Drug doses were sotalol 100 mg or lignocaine 100 mg, given as i.v. boluses. A further 2 min of cardiopulmonary resuscitation was given and then defibrillation was repeated twice. If this failed, half the initial dose of the trial drug was repeated and a further > or = 2 shocks were given. RESULTS: Sixty patients were randomized to sotalol and 69 randomized to lignocaine. There was no significant difference between the two groups in the clinical characteristics of the patients or in the number of shocks received. Outcomes in the sotalol and lignocaine groups were survival to hospital admission in 7 (12%) and 16 (23%), respectively (P = 0.09), and survival to hospital discharge in 2 (3%) and 5 (7%), respectively (P = 0.33). CONCLUSIONS: Sotalol is not superior to lignocaine for treatment of ventricular fibrillation refractory to multiple shocks. The overall outcome of this group of patients is poor regardless of the pharmacological intervention (lignocaine or sotalol).

Evaluation of the role of I(KACh) in atrial fibrillation using a mouse knockout model.

OBJECTIVES: We sought to study the role of I(KACh) in atrial fibrillation (AF) and the potential electrophysiologic effects of a specific I(KACh) antagonist. BACKGROUND: I(KACh) mediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of I(KACh) in the generation of AF and the electrophysiologic effects of specific I(KACh) blockade have not been studied. METHODS: Adult wild-type (WT) and I(KACh)-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific I(KACh) antagonist. RESULTS: Atrial fibrillation lasting for a mean of 5.7+/-11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function. CONCLUSIONS: Activation of I(KACh) predisposed to AF and lack of I(KACh) prevented AF. It is likely that I(KACh) plays a crucial role in the generation of AF in mice. Specific I(KACh) blockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles.

Induction of atrial tachycardia and fibrillation in the mouse heart.

BACKGROUND: Atrial tachycardia and fibrillation in humans may be partly consequent to vagal stimulation. Induction of fibrillation in the small heart is considered to be impossible due to lack of a critical mass of > 100-200 mm2. Even with the recent progression of the technology of in vivo and in vitro mouse electrophysiological studies, few reports describe atrial tachycardia or fibrillation in mice. The purpose of this study was to attempt provocation of atrial tachyarrhythmia in mice using transvenous pacing following cholinergic stimulation. METHODS AND RESULTS: In vivo electrophysiology studies were performed in 14 normal mice. A six-lead ECG was recorded from surface limb leads, and an octapolar electrode catheter was inserted via jugular vein cutdown approach for simultaneous atrial and ventricular endocardial recording and pacing. Atrial tachycardia and fibrillation were inducible in one mouse at baseline electrophysiology study and eleven of fourteen mice after carbamyl choline injection. The mean duration of atrial tachycardia was 126 +/- 384 s. The longest episode lasted 35 min and only terminated after atropine injection. Reinduction of atrial tachycardia after administration of atropine was not possible. CONCLUSION: Despite the small mass of the normal mouse atria, sustained atrial tachycardia and fibrillation can be easily and reproducibly inducible with endocardial pacing after cholinergic agonist administration. This finding may contribute to our understanding of the classical theories of arrhythmogenesis and critical substrates necessary for sustaining microreentrant circuits. The techniques of transcatheter parasympathetic agonist-mediated atrial tachycardia induction may be valuable in further murine electrophysiological studies, especially mutant models with potential atrial arrhythmia phenotypes.

A switch mechanism for G beta gamma activation of I(KACh).

G protein-gated inwardly rectifying potassium (GIRK) channels are a family of K(+)-selective ion channels that slow the firing rate of neurons and cardiac myocytes. GIRK channels are directly bound and activated by the G protein G beta gamma subunit. As heterotetramers, they comprise the GIRK1 and the GIRK2, -3, or -4 subunits. Here we show that GIRK1 but not the GIRK4 subunit is phosphorylated when heterologously expressed. We found also that phosphatase PP2A dephosphorylation of a protein in the excised patch abrogates channel activation by G beta gamma. Experiments with the truncated molecule demonstrated that the GIRK1 C-terminal is critical for both channel phosphorylation and channel regulation by protein phosphorylation, but the critical phosphorylation sites were not located on the C terminus. These data provide evidence for a novel switch mechanism in which protein phosphorylation enables G beta gamma gating of the channel complex.

Comparison of sotalol with amiodarone for long-term treatment of spontaneous sustained ventricular tachyarrhythmia based on coronary artery disease.

AIM: To compare the efficacy of sotalol versus amiodarone for long-term treatment of ventricular tachyarrhythmias. METHODS: Patients (n=75) with spontaneous, sustained ventricular tachyarrhythmias secondary to remote myocardial infarction were studied. After intravenous electrophysiological testing, both sotalol and amiodarone were predicted to be ineffective in 50 (67%) patients. Five patients were excluded. Forty-five patients were randomized to receive sotalol (n=22) or amiodarone (n=23) for maintenance therapy. The primary outcome variable was the time to first recurrence of sustained ventricular tachyarrhythmia. RESULTS: At 36 months. 75% of those allocated sotalol remained free of ventricular tachyarrhythmia compared with 38% of those allocated amiodarone (P=0.05). On multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for patients on amiodarone was 5.9 times higher (P=0.008) than that for patients on sotalol. CONCLUSION: Sotalol is superior to amiodarone for long-term treatment of ventricular tachyarrhythmia secondary to coronary artery disease when both drugs have been predicted to be ineffective at intravenous electrophysiological testing. Randomized trials in larger numbers of patients with ventricular tachyarrhythmia need to be performed comparing the two agents directly.

Comparison of the long-term efficacy of implantable defibrillators and sotalol for documented spontaneous sustained ventricular tachyarrhythmias secondary to coronary artery disease.

BACKGROUND: The relative efficacy of antitachycardia pacing implantable cardioverter defibrillators (ATPICD) and sotalol in the treatment of ventricular tachyarrhythmias is controversial. AIM: To compare the mortality in patients treated with ATPICD and sotalol for documented spontaneous sustained ventricular tachyarrhythmias occurring late after previous myocardial infarction. METHODS: In this non-randomised retrospective study of 139 consecutive patients all patients had inducible ventricular tachycardia at baseline electrophysiological studies. Before the availability of ATPICD, 22 patients were treated with sotalol as part of a randomised study comparing the efficacy of sotalol to amiodarone. After ATPICD became available sotalol was used in 49 patients in whom intravenous testing predicted sotalol to be effective and ATPICD were implanted in 68 patients in whom sotalol was predicted to be ineffective at electrophysiological testing. Thus, 68 patients were treated with an ATPICD and 71 with sotalol. RESULTS: The two groups were well-matched for age, type of presenting arrhythmia, severity of coronary artery disease and ventricular function. At 36 months Kaplan-Meier estimates of mortality from ventricular tachyarrhythmia were 0% with ATPICD and 15% with sotalol (p=0.03). Kaplan-Meier estimates of total mortality at 36 months were 12% with ATPICD and 25% with sotalol (p=0.09). Multivariate analysis showed hazard ratio of 7.9 (p=0.06) for death from ventricular tachyarrhythmia in patients treated with sotalol compared to ATPICD. CONCLUSIONS: While no difference in total mortality was demonstrated, treatment with ATPICD is probably superior to sotalol for preventing deaths due to ventricular tachyarrhythmia.

Risk to patients from radiation associated with radiofrequency ablation for supraventricular tachycardia.

BACKGROUND: Radiofrequency ablation may be associated with prolonged fluoroscopy times. Previous studies have calculated radiation risks by measuring the radiation dose at a limited number (6) of body sites. This is an inherently inaccurate measure. Our study aimed to quantify more precisely patient-related radiation risks associated with radiofrequency ablation for supraventricular tachycardia. METHODS AND RESULTS: Nine female patients having radiofrequency ablation for supraventricular tachycardia were studied. The radiation dose was determined at 41 body sites in each patient with the use of thermoluminescent dosimeters and was correlated with that measured simultaneously with a Diamentor dose-area product meter. The estimated mean organ doses (mGy) per 60 minutes of fluoroscopy were: lungs 30.8; bone marrow 4.3; left breast 5.1; right breast 3. 5; and thyroid 2.4. From the average organ doses, the estimated mean total lifetime excess risk of a fatal malignancy was 294 per million cases (0.03%) per 60 minutes of fluoroscopy. The risk calculation from the Diamentor dose-area product and thermoluminescent dosimeters were similar, suggesting that radiation dose was measured accurately. The estimated risk of radiation-induced malignancy increased with increasing body mass index (P=0.03). CONCLUSIONS: Prolonged fluoroscopy during radiofrequency ablation may potentially cause a small increase in the lifetime risk of fatal malignancy, with lung malignancy being most likely. This risk is small only with the use of techniques and x-ray equipment optimized to keep radiation as low as possible. The risk is increased in obese patients.

Efficacy and safety of a new protocol for continuous infusion of midazolam and fentanyl and its effects on patient distress during electrophysiological studies.

Electrophysiological studies are often distressing for patients. We devised a regime of continuous infusion of midazolam and fentanyl during electrophysiological studies without the presence of a specialist anaesthetist. The effects on key hemodynamic and respiratory variables and level of sedation were evaluated in detail in the first 775 patients. The safety of this practice was evaluated in 1,344 consecutive patients. Doses were calculated according to patients' weight and age. A mean total dose of 26 mg of midazolam and 115 mcg of fentanyl were infused. Satisfactory sedation was achieved in 97% of patients. The mean duration of procedure was 188 +/- 90 minutes. Complete amnesia of the procedure was obtained in 87% of patients. Sedation caused clinically insignificant changes in respiratory rate, oxygen saturation, end-tidal CO2 and blood pressure. There were no major complications related to sedation. Upper airway obstruction, usually minor, occurred in 42% and some restlessness in 20% of sedated patients. The assistance of a specialist anesthetist was required in 0.3% of sedated patients for management of restlessness, hypoventilation, or obstructive sleep apnea. The amount of distress experienced by sedated patients (n = 775) was significantly less compared to a previous series of nonsedated patients (n = 775) undergoing electrophysiological studies (P < 0.001). The degree of distress experienced by patients during electrophysiological studies can be reduced significantly by sedation with intravenous midazolam and fentanyl. Continuous infusion is an efficient, safe, and effective way of administering midazolam and fentanyl.

Does sotalol have reverse-use dependence during tachyarrhythmias?

This study assessed the effect of intravenous sotalol on right ventricular effective refractory period at right ventricular pacing rates of 600 and 300 ms cycle length at 3, 6, 9, and approximately 30 minutes after the dose of sotalol. Similar percent increases occurred in the ventricular effective period at the 2 heart rates at all tested times (p >0.2 in each case), and it was concluded that there is no evidence for reverse-use dependence of intravenous sotalol in its effects on right ventricular refractoriness over this range of heart rates.

Radiation exposure to patient and operator during radiofrequency ablation for supraventricular tachycardia.

BACKGROUND: Radiofrequency (RF) ablation has become the primary method of treatment for supraventricular tachycardia and often requires prolonged fluoroscopy times. AIM: To quantitate radiation exposure to patient and operator during RF ablation for supraventricular tachycardia. METHODS: Thermoluminescent dosemeters were used to monitor radiation at seven sites. Positions were: patient's thyroid, left scapula, T9 vertebra, right scapula and L4-L5 vertebra and the operator's thyroid and left hand. Monitoring was performed during 22 procedures. Of the patients studied 10 (45%) had atrioventricular junctional re-entry tachycardia (AVJRT) and 12 (55%) had accessory pathway tachycardia. RESULTS: The median fluoroscopy times (minutes) and inter-quartile ranges were 46 (39-65) for AVJRT, 55 (52-60) for left free wall accessory pathway (LFW), 107 (89-140) for septal and 166 (128-176) for RFW pathways. The mean radiation doses (mGy) to the chest wall were 50 for AVJRT, 47 for LFW, 87 for septal and 151 for RFW pathways. The mean radiation to the chest wall of the patient per case was found to be 3.9 times that reported for diagnostic cardiac catheterisation and 1.5 times that reported for angioplasty. CONCLUSIONS: Radiofrequency ablation is associated with significant irradiation of the patient and operator. All precautions should be taken to decrease this exposure. If eye irradiation is assumed to be equal to that to the thyroid, more than 45 procedures per month by a single operator (using ceiling-suspended lead glass shielding) may result in exceeding the recommended dose limit to the eye.

Cardiac electrophysiologic effects of midazolam combined with fentanyl.

Midazolam and fentanyl together produce better sedation, analgesia and amnesia than do either drug alone, but the electrophysiologic effects of the combination are unknown. Twenty patients undergoing electrophysiologic studies for clinical reasons were studied. Blood pressure, heart rate, respiratory rate, oxygen saturation, and standard variables related to atrioventricular and ventriculoatrial conduction, dual pathways, accessory pathway conduction, sinus node function, and the inducibility of tachycardia were examined before and after intravenous injections of midazolam (0.07 +/- 0.03 mg/kg) combined with fentanyl (0.8 +/- 0.4 micrograms/kg). There were no significant changes in the electrophysiologic variables or ease of inducibility of tachycardia. The drugs were well tolerated; they produced minor and clinically unimportant reductions in mean blood pressure (99 +/- 13 to 89 +/- 16 mm Hg; p < 0.001) and respiratory rate (18 +/- 4 to 16 +/- 3 breaths/min; p = 0.05). Excellent sedation was achieved. Major amnesia was reported by 95% of patients. In conclusion, midazolam combined with fentanyl provides safe and effective sedation for electrophysiologic studies without significantly affecting electrophysiologic variables or the inducibility of tachyarrhythmias.