Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans.

OBJECTIVES: This study investigated the efficacy and tolerability of low energy shocks for termination of atrial fibrillation in patients, using an endocardial electrode configuration that embraced both atria. BACKGROUND: In animals, low energy biphasic shocks delivered between electrodes in the coronary sinus and right atrium have effectively terminated atrial fibrillation. If human defibrillation thresholds are sufficiently low, atrial defibrillation could be achieved in conscious patients using an implanted device. METHODS: Twenty-two consecutive patients with stable atrial fibrillation were studied during electrophysiologic testing. Biphasic R wave synchronous shocks were delivered between large surface area electrodes in the coronary sinus and high right atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to a maximum of 400 V. Patients were conscious at the start of the study and were asked to report on symptoms but were sedated later if shocks were not tolerated. RESULTS: Cardioversion was achieved in all 19 patients who completed the study, with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia or mechanical complications occurred. CONCLUSIONS: The delivery of biphasic R wave synchronous shocks between the high right atrium and coronary sinus can terminate atrial fibrillation with very low energies. General anaesthesia is not required, and a minority of fully conscious patients are able to tolerate this method of cardioversion.

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.

Usefulness of signal-averaged electrocardiogram in idiopathic dilated cardiomyopathy for identifying patients with ventricular arrhythmias.

In idiopathic dilated cardiomyopathy (IDC), the relation between the signal-averaged electrocardiogram and ventricular tachycardia (VT) remains unclear. In this study, conventional time domain and frequency domain analyses (2-dimensional, spectral temporal mapping and spectral turbulence analysis) of the signal-averaged electrocardiogram were performed in 64 patients with IDC. Eight patients had a history of symptomatic sustained VT and an additional 24 had nonsustained VT recorded during ambulatory electrocardiography. Conventional time domain analysis, using the 25 and 40 Hz filter, and spectral temporal mapping, detected late potentials within the terminal QRS in 8 (13%), 14 (22%) and 18 (28%) patients, respectively. Late potentials were seen more often in patients with than without VT, and in patients with sustained versus nonsustained VT, but these differences were not significant. The predictive accuracy of these techniques in detecting either form of VT were: sensitivity, 22, 25 and 31%; specificity, 97, 81 and 75%; and overall predictive value, 59, 53 and 50%, respectively. Two-dimensional frequency domain analysis of the signal-averaged electrocardiogram revealed a higher energy and area ratio in patients with than without VT (entire QRS), and in patients with sustained versus nonsustained VT (entire QRS and terminal QRS). Spectral turbulence analysis was abnormal in 24 patients (39%), but no differences were observed between patients with and without VT. During follow-up (mean duration 18 +/- 14 months), 5 patients had arrhythmic events (3 died suddenly, 1 had aborted sudden death and 1 developed sustained VT).(ABSTRACT TRUNCATED AT 250 WORDS)

DDD pacing in hypertrophic cardiomyopathy: a multicentre clinical experience.

BACKGROUND: DDD pacing has been advocated as an effective treatment for drug refractory obstructive hypertrophic cardiomyopathy. This study reports the outcome of pacing in 56 patients with refractory symptoms referred to four tertiary centres. METHODS: Core data on symptoms, drug burden, and left ventricular outflow tract gradient were recorded. Patients underwent a temporary pacing study with optimisation of the atrioventricular (AV) delay for greatest gradient reduction without haemodynamic compromise. Patients were assessed after implantation in terms of changes in symptoms, drug load, and outflow tract gradient. RESULTS: 56 patients underwent pacing assessment. The mean (SD) left ventricular outflow tract gradient before pacing was 78 (31) mm Hg. At temporary study the mean (SD) left ventricular outflow tract gradient was 38 (24) mm Hg with a median (range) optimised sensed AV delay of 65 (25-125) ms. Fifty three patients were implanted and followed up for a mean (SD) of 11 (11) months. The median (range) programmed sensed AV delay was 60 (31-200) ms. Left ventricular outflow tract gradient at follow up was 36 (25) mm Hg. Forty four patients had improved functional class. Although a correlation (r = 0.69) was shown between acute and chronic left ventricular outflow tract gradient reduction, there was no correlation between magnitude of gradient reduction and functional improvement, and no appreciable change in pharmacological burden. CONCLUSION: This series confirms symptomatic improvement after DDD pacing in hypertrophic cardiomyopathy. There remains, however, a discrepancy between perceived symptomatic benefit and modest objective improvement. Furthermore, the optimal outcome has been achieved only with continued pharmacological treatment. Current methods of temporary evaluation do not predict functional outcome which seems to be independent of the magnitude of gradient reduction.

Low energy internal cardioversion of atrial fibrillation resistant to transthoracic shocks.

OBJECTIVE: To investigate the efficacy of internal cardioversion using low energy shocks delivered with a biatrial electrode configuration in chronic atrial fibrillation resistant to transthoracic shocks. METHODS: Low energy internal cardioversion was attempted in 11 patients who had been in atrial fibrillation for 233 (SD 193) days and had failed to cardiovert with transthoracic shocks of 360 J in both apex-base and anterior-posterior positions. Synchronised biphasic shocks of up to 400 V (approximately 6 J) were delivered, usually with intravenous sedation only, between high surface area electrodes in the right atrium and the left atrium (coronary sinus in nine, left pulmonary artery in one, left atrium via patent foramen ovale in one). RESULTS: Sinus rhythm was restored in 8/11 patients. The mean leading edge voltage of successful shocks was 363 (46) V [4.9 (1.2) J]. Higher energy shocks induced transient bradycardia [time to first R wave 1955 (218) ms]. No proarrhythmia or other acute complications were observed. CONCLUSIONS: Low energy internal cardioversion of atrial fibrillation can restore sinus rhythm in patients in whom conventional transthoracic shocks have failed.

Risk assessment and prevention of sudden cardiac death in hypertrophic cardiomyopathy.

One of the principle aims in the assessment of the patient with hypertrophic cardiomyopathy is assessment of risk for sudden cardiac death. Conventional risk stratification is reviewed together with other non-invasive techniques such as exercise physiology; the signal averaged electrocardiogram and heart rate variability. The role of arrhythmias in the pathogenesis of sudden cardiac death in hypertrophic cardiomyopathy is reviewed together with the role of programmed ventricular stimulation. A novel electrophysiological technique is described in detail which aims to measure the electrophysiological effects of myocardial disarray and seems safer and more sensitive and specific than conventional electrophysiological techniques. Current therapeutic strategies are discussed including the role of drugs, the implantable cardioverter defibrillator, surgery and dual chamber pacing.

Arrhythmia and hypertrophic cardiomyopathy.

Atrial fibrillation is the commonest arrhythmia observed in hypertrophic cardiomyopathy, and is associated with an acute deterioration in symptoms. Digoxin is the drug of choice in established atrial fibrillation and amiodarone the drug of choice in paroxysmal atrial fibrillation and ventricular arrhythmia. Non-sustained ventricular tachycardia occurs in 20% of patients and is the single best predictor of sudden death in adults. Sustained monomorphic ventricular tachycardia occurs only rarely. The mechanism of sudden death is likely to involve initiating factors such as arrhythmia and peripheral autonomic dysfunction causing haemodynamic instability and myocardial ischaemia. Myocardial disarray may provide the arrhythmogenic substrate such that haemodynamic instability and ischaemia results in ventricular fibrillation and sudden death.

Proarrhythmic effect of adenosine in a patient with atrial flutter.

Adenosine has been proposed as a useful diagnostic agent in patients with narrow complex regular tachycardia of uncertain origin. Its effects are usually transient owing to its extremely short plasma half life and, as a consequence, it is thought to be safer than other drugs used in the acute treatment of such arrhythmias. However, adenosine had a proarrhythmic effect when administered to a patient in order to confirm the diagnosis of atrial flutter. As expected, a transient increase in atrioventricular block was seen but this was followed by a doubling of the ventricular rate and haemodynamic compromise requiring immediate DC cardioversion. It is postulated that the secondary catecholamine-mediated effects of adenosine were responsible for this phenomenon.

The arrhythmogenic substrate--diagnostic and therapeutic implications: hypertrophic cardiomyopathy.

Hypertropic cardiomyopathy provides an important model for the study of mechanisms of sudden death. Initiating factors for sudden cardiac death may include sinus tachycardia and paroxysmal supraventricular arrhythmias. The haemodynamic effects of such triggers may be modulated depending on the patients exercise haemodynamics, peripheral vasomotor control and autonomic function. Myocardial disarray provides the underlying histological substrate for the lethal ventricular arrhythmias that represent the final common pathway. Attempts at individual risk stratification for sudden cardiac death using conventional risk factors and non-invasive techniques such as Holter monitoring identify a large group of patients, many of whom will not experience sudden cardiac death. Conventional electrophysiological methods such as programmed ventricular stimulation do not add to risk stratification inducing a variety of non-sustained or non-specific ventricular arrhythmias. A novel electrophysiological technique described in this article offers more promise in this regard.

Pseudoxanthoma elasticum presenting with myocardial infarction.

A 31 year old man presented with an anterior myocardial infarction. He had a history of recurrent gastrointestinal bleeding of obscure cause since childhood and peripheral vascular disease. A clinical diagnosis of the type 1 dominant form of pseudoxanthoma elasticum was supported by histological data from skin biopsy.

New algorithms to increase the initial rate response in a minute volume rate adaptive pacemaker.

BACKGROUND: Minute volume is a truly physiological sensor for rate adaptive pacing that correlates with metabolic expenditure throughout the range of physical activity. Criticism has centered on the slow initial response compared to less physiological sensors. A new algorithm, consisting of rate augmentation factor and programmable speed of response, has been incorporated in the 1206 META III pacemaker generator and was designed to improve the rate response at lower levels of exertions. Rate augmentation factor increases the programmed rate response factor by 3, 6, or 10 when set to low, medium, or high, respectively; this augmentation lasting to 50% of the maximum programmed rate. Response time can be programmed to medium or fast. METHODS: Nine patients were studied during the first 3 minutes of an exercise test (Bruce protocol) in a single blind manner. The pacemaker generator was randomly programmed with rate augmentation factor at off, low, or high and speed of response to medium or fast, giving six possible combinations. Heart rates were recorded continuously for the duration of the test and until resting heart rate was achieved during recovery. The test was repeated until all six combinations had been tested. RESULTS: During exercise significant differences appeared in response time from 30 seconds onward. Fast response and rate augmentation factor contributed to an improved rate response with greatest speed of response seen with fast response time and high rate augmentation factor. During recovery decreases in recovery time were seen with fast response time but rate augmentation factor prolonged recovery. CONCLUSIONS: Rate augmentation factor improves initial rate response in the early stages of exercise. Fast response gives an improved time to initial rate increase and shortens the duration of inappropriate postexercise tachycardia. These features improve the pattern of response of the minute ventilation sensor.

A new pacing algorithm for overdrive suppression of atrial fibrillation. Chorus Multicentre Study Group.

Constant rapid pacing may suppress arrhythmias, but it is usually poorly tolerated in the long term. We report a pilot study of a new pacing algorithm for overdrive suppression of atrial premature complexes (APCs) and atrial fibrillation (AF), which prevents postextrasystolic pauses and varies the pacing rate in response to the frequency of APCs. The algorithm was tested in a multiple crossover study for 24 hours in dual chamber pacemakers implanted in 70 patients. Comparison was made on ambulatory recordings between the number of atrial arrhythmias commencing with the algorithm active and inactive. In all cases, the algorithm functioned as designed. No patient was aware of its operation, and no malignant arrhythmias were induced. The 36 recordings that showed atrial arrhythmia were included for analysis. The effects of the algorithm were: APCs (estimated from pacemaker statistics) reduced in 18 patients, increased in 8 (P = 0.02); atrial salvos reduced in 12, increased in 4 (P = 0.041); and AF reduced in 11, increased in 8 (P = NS). In all patients with frequent AF (> 5 episodes in total), fewer episodes occurred when the algorithm was active. We conclude that the algorithm is safe and well tolerated, reduces atrial ectopic activity, and may reduce the frequency of sustained atrial fibrillation.

Ambulatory assessment of the QT interval in patients with hypertrophic cardiomyopathy: risk stratification and effect of low dose amiodarone.

This study aims to assess the dynamics of the QT interval in patients with hypertrophic cardiomyopathy (HCM). Three consecutive QT intervals and the preceding RR intervals were measured on 24 hour ambulatory electrocardiograms at 30-minute intervals in ten high risk patients with HCM (sudden cardiac death [SCD] and/or documented ventricular fibrillation), aged 29 +/- 17 years, compared with ten age and sex matched low risk patients with HCM (no syncope, no adverse family history, and no ventricular tachycardia on Holter monitoring), and ten normal subjects. Another ten patients who were on amiodarone therapy (200-mg daily) were also studied. Patients with intraventricular conduction defects were excluded. There were 4,424 pairs of QT intervals and their preceding RR intervals were measured in this study. A nonsignificant prolongation in the QT interval and a significant prolongation in QTc values (Bazett's and Fridericia's formulas) were demonstrated in patients with HCM compared with normals. There were no significant differences in the QT and QTc between high and low risk patients. The slope of regression line for the QT against RR interval was significantly different between normals and HCM (0.1583 +/- 0.040 vs. 0.2017 +/- 0.043, P < 0.05), but not between high and low risk patients. Amiodarone significantly prolonged the QT and QTc without significantly altering the slope of the regression line (0.2017 +/- 0.043 vs 0.2099 +/- 0.037, NS). Our findings support the observations that there is a prolonged QT interval in patients with HCM and that there is no significant use dependent effect of amiodarone on ventricular repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of paced electrogram fractionation in hypertrophic cardiomyopathy. A prospective study.

BACKGROUND: Increased duration of paced right ventricular (RV) electrograms in hypertrophic cardiomyopathy has been shown in 37 patients to correlate with the risk of ventricular fibrillation (VF). The changes in electrogram duration with pacing stimulus prematurity discriminated patients into three groups: VF survivors, an intermediate group with either non-sustained ventricular tachycardia (NSVT) on ambulatory monitoring or a family history of sudden death (FHSD), and those with none of these risk factors (noRF) for sudden death (SD). The consistency of these original groups has been tested prospectively in a further 64 patients. METHODS AND RESULTS: Of 64 patients with hypertrophic cardiomyopathy, 3 had documented VF, 1 had witnessed SD and is assumed to have had VF, 25 had NSVT, 21 had FHSD, and 14 had noRF. Nineteen patients had syncope. They were studied by pacing one RV site with a decremental sequence and recording high-pass filtered electrograms from three other RV sites. The delay of each fractionated potential in the electrogram was determined relative to a pacing stimulus of increasing prematurity. These measurements were repeated by pacing each ventricular site in turn. The electrograms were characterized by two parameters: the extrastimulus coupling interval (S1S2) at which delay increased by more than 0.75 ms/20 ms decrease in S1S2 interval and the change in electrogram duration between an S1S2 of 350 ms and ventricular effective refractory period. The 4 VF patients had a mean increase in electrogram duration of 16.1 ms and an increase in delay at a mean S1S2 of 368 ms. Three VF patients were within the original VF group, while only 6 of 60 non-VF patients were within this group, discriminating between VF patients and the remainder (P < .007). The 14 noRF patients had a mean change in electrogram duration of 4.5 ms and an increase in delay at a mean S1S2 of 301 ms. Eleven patients were within the original noRF group, and only 8 of the remaining 50 patients also were within the noRF group, discriminating between the noRF patients and the remainder (P < .0005). Most of the NSVT and FHSD patients were between the original VF and noRF groups, with 5 of 25 NSVT and 1 of 31 FHSD patients in the original VF group. There was no relation between syncope and electrophysiological characteristics. Programmed electrical stimulation (PES) was performed in the first 15 patients of this study. Of the total 52 patients from the original and current studies, PES identified 2 out of 6 VF patients, and there was no correlation between VF inducibility and intraventricular conduction delay. CONCLUSIONS: These data are consistent with the original VF and noRF groups. Most patients with FHSD or NSVT were between these groups. Pooled data from the original and current groups (n = 101) allow definition of a new VF group, which includes all patients with VF (n = 9), 8 of 30 patients with VT, and 3 of 31 patients with FHSD. This new group may be used as a criterion for implantable cardioverter-defibrillator implantation in a prospective trial of the technique for the prediction of SD.

Prognosis of idiopathic dilated cardiomyopathy.

Previous reports in referral populations have emphasized the poor prognosis of dilated cardiomyopathy. This study evaluated mortality and morbidity in patients presenting at a referral center between 1989 and 1993. One hundred seventy-two consecutive patients were studied. At presentation, 82 were in New York Heart Association functional class III/IV. Mean (+/- SD) left ventricular end-diastolic dimension was 69 +/- 11 mm, ejection fraction was 25 +/- 10%, VO2 max was 21 +/- 9 mL/min/kg, and sodium was 136 +/- 9 mM. Treatments included vasodilators (n = 157, 92%), anticoagulation (n = 50, 29%), amiodarone (n = 52, 30%), and cardiac defibrillator (n = 5, 3%). During the follow-up period (mean, 26 +/- 29 months), 16 patients died and 60 developed progressive heart failure; 46 (27%) required cardiac transplantation. The majority of the patients (102, 59%) were stable or improved. Established prognostic determinants (left ventricular end-diastolic dimension, ejection fraction, sodium, and arrhythmia) were of low predictive value for the development of progressive heart failure or sudden death. The 1- and 2-year probabilities of death or transplantation was 16 and 21%, respectively (death only 6 and 7%, respectively). These observations are subject to referral bias, but suggest that the majority of patients can remain stable. Any improvement in survival compared to earlier experience can be due to earlier diagnosis, availability of transplantation, and new heart failure management strategies.

Primary ventricular fibrillation is associated with increased paced right ventricular electrogram fractionation.

BACKGROUND: The mechanisms of spontaneous ventricular fibrillation (primary VF) in patients without structural heart disease are obscure. A new technique has shown that in patients with hypertrophic cardiomyopathy conduction of fractionated ventricular paced beats, recorded at several right ventricular sites, is prolonged in individuals who have suffered a VF arrest, and this may reveal one component of a reentrant substrate. Patients with primary VF were studied with the same methods to determine whether similar abnormalities are present in this group. METHODS AND RESULTS: Nine patients with primary VF were studied by pacing one right ventricular (RV) site by use of a constant drive train with an extrastimulus inserted every third beat and reducing the extrastimulus coupling interval (S1S2 interval) by 1 ms on each occasion while recording at three other sites. The delay of each fractionated potential in the high-pass-filtered electrograms in response to the extrastimulus was determined and used to form conduction curves of delay versus the S1S2 interval. These curves were repeated by pacing each RV site in turn and recording from the other three sites. The curves were characterized by determining the S1S2 interval at which electrogram components increased in delay by 0.75 ms/20 ms reduction in S1S2 interval and the increase in electrogram duration between a coupling interval of 350 ms and 1 ms above refractoriness. Seven control patients were studied using the same method. The mean increase in electrogram duration in VF patients was 13 ms (range, 3 to 23 ms) compared with 4 ms (range, -2 to 14 ms) in unaffected control patients. The extrastimulus coupling interval at which delay increased was 318 ms (range, 293 to 334 ms) in VF patients and 274 ms (range, 265 to 284 ms) in control patients (P < .01). There was no difference between the number of fractionated potentials in VF patients and control patients. CONCLUSIONS: In primary VF patients, the individual potentials within fractionated electrograms have increased delays when compared with control patients. This may identify one component of a reentrant arrhythmic substrate.

Femoral arterial hemostasis using a collagen plug after coronary artery stent implantation.

We have investigated the safety and efficacy of sealing the femoral arterial puncture site using purified bovine collagen in the catheter laboratory immediately after coronary stent implantation. Ten consecutive patients, mean age 64.6 years, pretreated with heparin, aspirin, and dextran underwent the insertion of a collagen plug immediately after coronary stent implantation. The mean activated clotting time was 512 seconds (range 320-999). Femoral arterial hemostasis was achieved before leaving the catheterization laboratory in nine of ten patients. Seven of these patients received additional mild groin compression with an air cushion compression device after hemostasis was successful. One of ten patients had persistent bleeding after delivery of the collagen plug and later required blood transfusion. The collagen plug may be a useful adjunct to obtaining hemostasis following coronary stent implantation, but further trials are required to test its reliability in fully anticoagulated patients.

Chest pain during daily life in patients with hypertrophic cardiomyopathy: an ambulatory electrocardiographic study.

Patients with hypertrophic cardiomyopathy frequently complain of chest pain during daily activities. ST-segment depression is described in association with sudden death and pacing, but its prevalence during ambulatory electrocardiographic monitoring is unknown. The aim of this study was to determine the relation of ambulatory ST-segment depression to clinical characteristics, risk factors for sudden death and thallium-201 perfusion in patients with hypertrophic cardiomyopathy. Continuous 48 h ambulatory electrocardiographic monitoring was performed in 113 patients (age 38 +/- 14 years) with hypertrophic cardiomyopathy. Ninety-four (83%) recordings were suitable for ST-segment analysis. A total of 109 episodes of ST-segment depression (> or = 1 mm from baseline) were recorded in 25 (27%) patients (mean 4 +/- 5). In patients < or = 30 years of age (but not > 30) there was an association between ST-segment depression and a history of exertional chest pain (seven of 12 vs one of 20; P = 0.001), and dyspnoea NYHA class II/III (seven of 15 vs one of 17; P = 0.008). There was no association between ST-segment depression and risk markers for sudden death, i.e. family history of sudden death, syncope and non-sustained ventricular tachycardia, in any group. Reversible thallium-201 defects occurred in 27 (29%) of the 94 patients with analysed recordings but were not associated with symptoms, risk factors for sudden death or ambulatory ST-segment depression. In young patients with hypertrophic cardiomyopathy, ischaemia-like ST-segment depression is common and is associated with a history of typical angina and dyspnoea. Reversible thallium-201 perfusion defects are associated with neither symptomatic status nor ambulatory ST-segment depression.