Rapid access arrhythmia clinic for the diagnosis and management of new arrhythmias presenting in the community: a prospective, descriptive study.

OBJECTIVE: To investigate whether a rapid access approach is useful for the evaluation of patients with symptoms suggestive of a new cardiac arrhythmia. DESIGN: Prospective, descriptive study. SETTING: Secondary care based rapid access arrhythmia clinic in West London, UK. PARTICIPANTS: Patients referred by their general practitioner or the emergency department with symptoms suggestive of a new cardiac arrhythmia. MAIN OUTCOME MEASURES: Number of patients with a newly diagnosed significant arrhythmia. Number of patients with diagnosed atrial fibrillation. Number of eligible, moderate, and high risk patients treated with warfarin. RESULTS: Over a 25 month period 984 referrals were assessed. The mean age was 55 years (range 20-90 years) and 56% were women. The median time from referral to assessment was one day. A significant cardiac arrhythmia was newly diagnosed in 40% of patients referred to the RAAC. The most common arrhythmia was atrial fibrillation, with 203 new cases (21%). Of these, 74% of eligible patients over 65 were treated with warfarin. Other arrhythmias diagnosed were supraventricular tachycardias (127 (13%)), conduction disorders (43 (4%)), and non-sustained ventricular tachycardia (21 (2%)). Vasovagal syncope was diagnosed for 53 patients (5%). The most frequent diagnosis was symptomatic ventricular and supraventricular extrasystoles (355 (36%)). CONCLUSION: A rapid access arrhythmia clinic is an innovative approach to the diagnosis and management of new cardiac arrhythmias in the community. It provides a rapid diagnosis, stratifies risk, and leads to prompt initiation of effective treatment for this population.

Catheter ablation for hemodynamically unstable monomorphic ventricular tachycardia.

INTRODUCTION: Hemodynamic collapse precludes extensive catheter mapping to identify focal target regions in many patients with ventricular tachycardia (VT) associated with heart disease. This study tested the feasibility of catheter ablation of poorly tolerated VTs by targeting a region identified during sinus rhythm. METHODS AND RESULTS: Ablation was attempted in five patients, ages 44 to 59 years, with left ventricular ejection fractions of 0.15 to 0.20 and poorly tolerated VT causing multiple implantable defibrillator therapies (6 to 30 episodes/month). VT was due to prior infarction in three patients and nonischemic cardiomyopathy in two. Target regions were sought that met the following criteria: (1) evidence of slow conduction from fractionated sinus rhythm electrograms and stimulus-QRS delays during pace mapping, and (2) evidence that the region contains the reentrant circuit exit from pace mapping. In 4 of 5 patients, a target region was identified and radiofrequency lesions applied. Ablation abolished all recurrences of VT in 3 of 4 patients during follow-up of 14 to 22 months. There were no complications. CONCLUSION: Ablation of poorly tolerated VT is feasible in some patients by mapping during sinus rhythm and performing ablation over a region of identifiable scar that contains abnormal conduction and a presumptive VT exit.

Differential nitric oxide synthase activity in ischemic and idiopathic dilated cardiomyopathy.

We measured plasma nitrite and interleukin 1beta levels in patients with idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, and in normal controls. Nitrite levels were abnormally high in both ischemic and idiopathic dilated cardiomyopathy, suggesting increased nitric oxide activity in these conditions.

Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence.

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation.

Angiographic characteristics of infarct-related and non-infarct-related stenoses in patients in whom stable angina progressed to acute myocardial infarction.

BACKGROUND: In patients with coronary artery disease, angiographic and postmortem studies have shown that coronary stenoses in infarct-related arteries often have complex morphology. It is not known whether in patients with multivessel disease stenosis morphology in non-infarct-related arteries is different from those of the infarct-related arteries. METHODS AND RESULTS: In 24 consecutive patients we examined the angiographic characteristics of both the infarct-related stenoses and non-infarct-related stenoses before and after spontaneous acute myocardial infarction, by visual inspection and computerized edge detection of coronary angiograms. Before myocardial infarction, the severity of the infarct-related stenoses was <50% in 14 patients and > or =50% in 10 patients (p=not significant) and of non-infarct-related stenoses was <50% in 16 and > or=50% in 13. A significantly greater proportion of infarct-related stenoses with severity > or =50% progressed to non-Q-wave than to Q-wave myocardial infarction (71% vs 50%, p < 0.05). Before myocardial infarction, the percentage of concentric, eccentric, and irregular infarct-related stenoses was 8%, 13%, and 50%, respectively, whereas in the non-infarct-related stenoses it was 62%, 17%, and 21%, respectively (p < 0.01). A similar proportion of irregular morphology progressed to Q-wave or non-Q-wave myocardial infarction. CONCLUSIONS: In patients with stable angina who had acute myocardial infarction develop, the infarct-related and non-infarct-related stenoses on average are similar in severity but different in morphology. Nonsevere stenoses more frequently progress to Q-wave than to non-Q-wave myocardial infarction.

Ablation therapy for cardiac arrhythmias.

Ablation has become an important and, in some cases, the first-line therapy for a number of tachyarrhythmias. The feasibility of treating arrhythmias with ablation was initially demonstrated with surgical ablation techniques. Recently, catheter ablation techniques have replaced the surgical approach in nearly all cases. Catheter ablation is highly effective for the Wolff-Parkinson-White syndrome, atrioventricular nodal reentry, and atrial ectopic tachycardia. It is effective for atrial flutter, although approximately one quarter of patients treated with catheter ablation continue to require therapy for concomitant atrial fibrillation. The surgical maze procedure has proved to be feasible for preventing atrial fibrillation. The risks and long-term efficacy of catheter ablation maze procedures for atrial fibrillation need to be defined. The efficacy of ablation for ventricular tachycardia varies with the type of tachycardia. Catheter ablation is very effective for the rare idiopathic ventricular tachycardias that occur in structurally normal hearts and for bundle-branch reentry ventricular tachycardia, which occurs most frequently in patients with dilated cardiomyopathy. When performed at an experienced center, surgical ablation is an excellent option for selected patients with ventricular tachycardia due to prior myocardial infarction who have a discrete aneurysm but otherwise well-preserved ventricular function. Catheter ablation shows promise for this arrhythmia, but it can be offered only to those patients who have relatively slow tachycardias that allow catheter mapping. Substantial advances in mapping and ablation technology will continue to occur, allowing nonpharmacologic control of cardiac arrhythmias to be achieved in an ever greater number of patients.

Effects of inhibition of nitric oxide synthesis in patients with coronary artery disease and stable angina.

AIMS: Inhibition of nitric oxide synthesis causes a decrease in the basal diameter of normal distal epicardial coronary arteries in normal subjects. The effects of inhibition of nitric oxide in atheromatous coronary arteries is unknown. This study assessed the effects of the inhibition of nitric oxide synthesis in epicardial coronary arteries in patients with coronary artery disease. METHODS AND RESULTS: The effects of an intracoronary infusion of NG-monomethyl-L-arginine (LNMMA, an inhibitor of nitric oxide synthesis), were studied in 13 patients with chronic stable angina and coronary artery disease. The diameter of angiographically normal proximal and distal segments and coronary stenoses was measured by quantitative angiography. In response to an LNMMA infusion of 16 mumol min-1 for 4 min there was a significant reduction (P < 0.01) in the luminal diameter of the distal segments of diseased arteries (from 1.32 +/- 0.07 to 1.17 +/- 0.06 mm) and at the site of stenosis (from 1.15 +/- 0.22 to 1.06 +/- 0.20 mm), but no change (P = NS) in the luminal diameter of the proximal segments (from 3.16 +/- 0.12 to 3.08 +/- 0.14 mm) of diseased arteries. CONCLUSIONS: The average effect of inhibition of basal nitric oxide synthesis in epicardial coronary arteries in patients with stable angina and coronary artery disease was only distal constriction. Coronary stenoses constricted at the highest LNMMA concentration.

Altered resistive vessel function after coronary angioplasty is not due to reduced production of nitric oxide.

BACKGROUND: The coronary vasodilator reserve with dipyridamole may be impaired immediately after successful angioplasty due to reduced endothelial production or release of nitric oxide. As the vasodilator response to exogenous nitrates is enhanced by endothelium removal or inhibition of nitric oxide synthesis, an increased vasodilator response to nitrovasodilators, such as nitroprusside, should occur. METHODS: The coronary vasodilator reserve (maximal/basel coronary blood flow) with intravenous dipyridamole (0.56 mg/min for 4 min) was measured by Doppler catheterization before and after angioplasty in 10 patients with single-vessel coronary disease. At peak dipyridamole effect, incremental doses of nitroprusside (4-50 micrograms/min) were given intracoronary until systolic blood pressure fell by > or = 5 mmHg. RESULTS: Before angioplasty, the coronary blood flow increased from 19.7 +/- 6.1 (mean +/- s.d.) at basal to 30.1 +/- 11.9 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.62 +/- 0.39 (range 1.20 - 1.96). After angioplasty, the coronary blood flow increased from 32.4 +/- 13.2 at basal to 53.4 +/- 23.3 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.77 +/- 0.64 (range 1.7-2.42). Sodium nitroprusside had no additional effect on coronary flow (49.5 +/- 20.4 and 52.2 +/- 18.0 ml/min) before and after a fall in systolic blood pressure, respectively. CONCLUSIONS: The vasodilator response to dipyridamole was markedly impaired immediately after successful angioplasty, and was not augmented by intracoronary nitroprusside. Thus, a reduced production or release of nitric oxide in the coronary circulation does not seem to be responsible for the impaired vasodilator response after angioplasty.

Myocardial beta adrenoceptor density in primary and secondary left ventricular hypertrophy.

OBJECTIVES: Myocardial beta-adrenoceptor density has been found to be reduced in hypertrophic cardiomyopathy, even when systolic function is preserved. Our purpose in the current study was to investigate whether beta-adrenoceptor down-regulation was unique to hypertrophic cardiomyopathy, or is also present in secondary myocardial hypertrophy. METHODS: Myocardial beta-adrenoceptor density was measured in 11 patients with hypertrophic cardiomyopathy, eight patients with left ventricular hypertrophy secondary to arterial hypertension or aortic valve disease and 18 normal control subjects, using positron emission tomography with 11C-CGP-12177 as the myocardial beta-adrenoceptor ligand. RESULTS: Reflecting the natural incidence of the conditions, the age of the hypertrophic cardiomyopathy patients was 37 (10) [mean (SD), range 20-51] years and that of the secondary hypertrophy patients 64 (18), [range 26-80] years; P < 0.01. The controls' ages were 50 (13), [range 21-65] years; however, since beta-adrenoceptor density is known to be influenced by age, the controls' data was split into groups matched to the hypertrophic cardiomyopathy and secondary hypertrophy patient sets. For the hypertrophic cardiomyopathy patients, mean left ventricular beta-adrenoceptor was 7.70 (1.86) pmol.g-1 compared to 10.17 (2.44) pmol.g-1 for a matched set of 15 controls; P < 0.01. In secondary left ventricular hypertrophy, beta-adrenoceptor was 6.35 (1.70) pmol.g-1 compared to 9.16 (2.00) pmol.g-1 for a matched set of 10 controls; P < 0.01. Plasma noradrenaline was 5.5 (2.2) nmol.l-1 in hypertrophic cardiomyopathy and 2.5 (1.0) nmol.l-1 for the matched controls; P < 0.01. The results for adrenaline were 2.2 (1.1) vs 0.4 (0.3) nmol.l-1 respectively; P < 0.001. For the secondary hypertrophy patients, the corresponding figures were 2.5 (1.2) vs 2.5 (1.0) nmol.l-1 for noradrenaline for patients and controls respectively (P = ns); and for adrenaline 0.2 (0.1) and 0.3 (0.2) nmol.l-1 respectively, P = ns. On multiple regression analysis, no relationships could be demonstrated amongst plasma catecholamines, beta-adrenoceptor, myocardial blood flow and echocardiographic E/A ratio and fractional shortening. CONCLUSION: Myocardial beta-adrenoceptor density appears to be comparably decreased in both primary and secondary left ventricular hypertrophy in the presence of preserved left ventricular systolic function.

Angiotensin II and contraction of isolated myocytes from human, guinea pig, and infarcted rat hearts.

The effects of angiotensin II on myocardial contractility were assessed in isolated cardiac myocyte preparations, using video microscopy with a computerized edge-detection system. Angiotensin II (1 nM-10 microM) did not affect the contraction of rat (n = 10), guinea pig (n = 11), or human ventricular myocytes (n = 8) or of human atrial myocytes (n = 12). Isoproterenol or raised extracellular calcium increased the contraction amplitude of the cardiac myocytes to a maximum of between 150 and 560% above basal, and there were corresponding increases in the velocities of contraction and relaxation. In rat and guinea pig ventricular myocytes 1 microM angiotensin II did not affect the inotropic response to isoproterenol. Seven days after left coronary artery ligation in seven rats, the basal contraction amplitude was reduced in myocytes from the infarcted region (4.0 +/- 1.9%) compared with the noninfarcted region (5.0 +/- 2.8%, P = 0.03) and with myocytes from six sham-operated hearts (5.0 +/- 2.8%, P = 0.03). There was a switch in myosin isoform expression from the V1 to the V3 isoform in myocytes from both the infarcted and noninfarcted regions. Angiotensin II (1 nM-10 microM) had no significant effect on the contraction characteristics of myocytes from the infarcted rat hearts. In conclusion, angiotensin II had no significant inotropic effect on isolated cardiac myocyte preparations from guinea pig ventricle, normal and infarcted rat ventricle, human ventricle, and human atrium.

Variable coronary vasomotor responses to acetylcholine in patients with normal coronary arteriograms: evidence for localised endothelial dysfunction.

OBJECTIVE: The vasomotor responses of the epicardial coronary arteries to acetylcholine were examined in patients with normal coronary arteries and chest pain. DESIGN: Quantitative angiography was used to measure minimum lumen diameter of proximal and distal coronary artery segments at baseline, during intracoronary infusion of acetylcholine (10(-7) - 10(-3) mol/l), and following an intracoronary bolus (2 mg) of isosorbide dinitrate. PATIENTS: Coronary arteriograms were obtained in 15 patients (mean (SEM) age 48 (10) years) with normal coronary arteries and chest pain. MAIN RESULTS: In response to the low concentrations of acetylcholine (10(-7) - 10(-6) mol/1) 20 (61%) distal and 11 (41%) proximal segments showed dilatation (group 1), whereas 13 (39%) distal segments and 14 (52%) proximal segments showed constriction (group 2) (P < 0.05 v group 1). In group 1, the maximum dilatation induced by acetylcholine in the proximal and distal segments was 7.83 (1.19)% and 11.6 (2.2)% respectively. In group 2, the maximum constriction at higher concentration was 16.55 (3.3)% and 33.11 (11.63)% in the proximal and distal segments respectively. The two different patterns of the vasomotor response coexisted in eight (53%) of the 15 patients. Intracoronary isosorbide dinitrate caused a greater increase in the coronary luminal diameter of distal segments than in proximal segments in group 1 (25.63 (5.16)% v 12.43 (3.48)%, P < 0.01) but not in group 2 (12.65 (2.53)% v 10.82 (3.33)%. CONCLUSIONS: Constriction and dilatation may occur in proximal and distal coronary artery segments, suggesting local areas of endothelial dysfunction, in response to acetylcholine in patients with chest pain and angiographically normal coronary arteries.

Regional changes in angiotensin II receptor density after experimental myocardial infarction.

The plasma and cardiac renin-angiotensin systems may be activated after myocardial infarction. The myocardium may therefore be exposed to increased concentrations of angiotension II, which may contribute to myocardial injury. The purpose of this study was to identify the potential sites of action of angiotensin II in the infarcted heart. Myocardial infarction was induced in rats by left coronary artery ligation, and the hearts were removed for study after 18 h, 7 days, or 8 months. The regional ventricular angiotensin II receptor density was assessed by [125I](Sar1,Ile8)angiotensin II binding and quantitative autoradiography. The [125I](Sar1,Ile8)angiotensin II binding was unchanged at 18 h, but was increased at 7 days in the infarcted region of the left ventricle (73.2 +/- 3.2 amol/mm2, mean +/- S.E.M.) compared with the non-infarcted region (1.6 +/- 0.2 amol/mm2, P < 0.0001) and with the left ventricular myocardium of sham-operated control animals (1.3 +/- 0.1 amol/mm2, P < 0.0001). The increased [125I](Sar1,Ile8)angiotensin II binding density was still present, but diminished, at 8 months after coronary ligation (49.0 +/- 5.7 amol/mm2, P < 0.0001 v control, P = 0.0058 v 7-day infarcts). The increased binding of [125I](Sar1,Ile8)angiotensin II was antagonised by losartan, an AT1 receptor antagonist, but not by an AT2 receptor antagonist. Microautoradiography of [125I](Sar1,Ile8) angiotensin II, and assessment of collagen deposition using picrosirius staining and immunostaining demonstrated that the regional increase in AT1 receptor density in the infarcted region of myocardium was associated with fibroblast infiltration and collagen deposition. The infarct scar and the cardiac fibroblasts within it express high levels of angiotension II receptors and therefore represent potential targets for the actions of angiotensin II after myocardial infarction.

Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy.

OBJECTIVE: To assess the relation between left ventricular function and myocardial beta adrenoceptor density. METHODS: 17 patients with hypertrophic cardiomyopathy, six with and 11 without heart failure, were studied. Left ventricular function was assessed by echocardiography, and myocardial beta adrenoceptors by positron emission tomography. Patient data were compared with those obtained in normal controls. RESULTS: Myocardial beta adrenoceptor density in the 17 patients was 7.00 (SD 1.90) pmol/g v 11.50 (2.18) pmol/g in normal controls (P < 0.01). beta Adrenoceptor density in the six patients with left ventricular failure was 5.61 (0.88) pmol/g v 7.71 (1.86) pmol/g in the 11 patients with normal ventricular function (P < 0.05), and there was a significant correlation (r = 0.52; P < 0.05) between left ventricular fractional shortening and myocardial beta adrenoceptor density. A positive correlation (r = 0.51; P < 0.05) was also found between myocardial beta adrenoceptor density and the E/A transmitral flow ratio, an index of left ventricular diastolic function. CONCLUSIONS: There is myocardial beta adrenoceptor downregulation in patients with hypertrophic cardiomyopathy with or without signs of heart failure.

Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction.

BACKGROUND: The ability of the coronary vascular bed to dilate and thus increase blood flow to the myocardium may be impaired in coronary artery disease, even in regions of myocardium supplied by an angiographically normal coronary artery. If this kind of vasomotor dysfunction was present or accentuated after acute myocardial infarction, it might influence the extent of ischemia and necrosis in areas not directly injured by the infarction. METHODS: We studied 13 patients (mean [+/- SD] age, 62 +/- 11 years) with single-vessel coronary artery disease after they had received thrombolytic therapy for myocardial infarction. Using positron-emission tomography (PET) with oxygen-15-labeled water, we measured regional myocardial blood flow under basal conditions and after the intravenous administration of dipyridamole (0.5 mg per kg of body weight over a period of four minutes) 8 +/- 3 days after infarction in all 13 patients (1-week study) and 6 +/- 2 months after infarction in 9 of the 13 (6-month study). On both occasions we measured blood flow both in the infarcted region and in a region of myocardium that was remote from the infarcted region and supplied by a normal artery. RESULTS: At the one-week PET study, the coronary vasodilator response (the ratio of the myocardial blood flow after the administration of dipyridamole to basal blood flow) was 1.12 +/- 0.50 in the infarct-related artery and 1.53 +/- 0.36 in the remote region (P = 0.015). At the six-month study, the coronary vasodilator response was 1.42 +/- 0.37 in the infarcted region and 2.19 +/- 0.69 in the remote region (P = 0.004 for the comparison with the infarcted region; P = 0.011 for the comparison with the remote region at the one-week study). The value in remote myocardium remained lower than that in similar regions in 10 control patients, who had single-vessel coronary artery disease but no evidence of myocardial infarction (3.17 +/- 0.72; P = 0.009). CONCLUSIONS: After acute myocardial infarction, there is a severe vasodilator abnormality involving not only resistance vessels in infarcted myocardium, but also those in myocardium perfused by normal coronary vessels. This dysfunction may affect the extent of myocardial ischemia and necrosis after coronary occlusion.

Ventricular tachycardia: an unusual pacemaker-mediated tachycardia.

A 74 year old man had recurrent ventricular tachycardia, which was well controlled with amiodarone, and complete heart block for which a VVI permanent pacing system had previously been implanted. After an elective increase in the programmed pacemaker rate from 70 to 82 beats/min, there was recurrence of frequent episodes of ventricular tachycardia. Each episode of tachycardia was initiated by a fusion beat consisting of a ventricular extrasystole and a paced beat. When the pacemaker rate was reprogrammed to 70 beats/min the episodes of tachycardia ceased abruptly. It is proposed that the fusion of a ventricular extrasystole with a pacemaker beat may have induced ventricular tachycardia, even though neither of these beats occurring separately was sufficient to cause this.

Phorbol ester enhances activation of adenylate cyclase in bovine aortic endothelial cells.

Endothelial cells possess beta-adrenoceptors linked to adenylate cyclase which may regulate several aspects of endothelial cell function. The potential for this second messenger system to be modulated by protein kinase C activity was investigated. Bovine aortic endothelial cells (BAECs) were cultured in the absence or presence of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. Basal and forskolin-, sodium fluoride (NaF)-, and isoproterenol-stimulated adenylate cyclase activity was measured in homogenates from BAECs. beta-adrenoceptor density on membranes from BAECs was measured by 125I-iodocyanopindolol binding. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of immunoprecipitated proteins was used to identify phosphorylated proteins. Pretreatment of BAECs with 100 nM PMA for 30 min increased basal adenylate cyclase activity above control levels, and also increased enzyme activity stimulated by forskolin, NaF, or isoproterenol. Pretreatment of BAECs for 60 min with 100 nM staurosporine, an inhibitor of protein kinase C, prevented the enhancement of adenylate cyclase activity caused by PMA. Treatment of BAECs with PMA did not trigger phosphorylation of the inhibitory guanine nucleotide-binding protein, and there was no change in BAEC beta-adrenoceptor density following PMA pretreatment. Exposure of BAECs to ATP or bradykinin did not mimic the effects of phorbol ester. In conclusion, activation of protein kinase C by PMA enhanced adenylate cyclase activity in BAECs. However, ATP and bradykinin which activate endothelial cell surface receptors linked to phospholipase C did not mimic this effect.