Guy A. Haywood

Assessment of heart rate variability in hypertrophic cardiomyopathy. Association with clinical and prognostic features.

BackgroundAltered vascular responses during exercise and disturbed responses to autonomic function testing have been documented in hypertrophic cardiomyopathy (HCM) and are associated with markers of an adverse prognosis. Reduced heart rate variability (HRV) and baroreflex sensitivity are predictors of increased risk of sudden death after myocardial infarction, but the value of these parameters in 11CM is unknown. Methods and ResultsTo determine the clinical significance of HRV and its relation to markers of electrical and hemodynamic instability in 1CM, the 24-hour Holter recordings of 104 patients in sinus rhythm and off medication were analyzed. Five nonspectral measures of HRV were computed. The frequency components ofHRVwere calculated by fast Fourier transformation of the RR time intervals; the areas under the low (0.04 to 0.15 Hz) and high (0.15 to 0.4 Hz) frequency portions of the spectrum were measured as indices of autonomic and specific vagal influences on HRV, respectively. Spectral and nonspectral measures were compared with clinical, echo/Doppler, and Holter variables. ANCOVA was performed to allow for the effect of age on differences between variables. Spectral and nonspectral measures of HRV were correlated (r>.65; Ps.001), indicating that the different time-domain and frequency parameters reflected similar measures ofHRY. Global measures ofHRV including the standard deviation of the mean ofRR intervals (SDRR) and the standard deviation of 5-minute mean RR intervals (SDANN) were increased in patients with an adverse family history of 1CM (173±67 vs 131±38 milliseconds, P=.001, and 158±66 vs 116+36 milliseconds, P=.004, respectively). In patients with exertional chest pain, global nonspectral measures were reduced compared with asymptomatic patients (118±31 vs 152±53 milliseconds, P=.006, and 105±30 vs 136±52 milliseconds, P=.014, respectively). Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (PNN5O) and the high frequency peak on spectral analysis were less in patients with supraventricular arrhythmias on Holter monitoring (7.2±8 vs 16±13%, P=.012, and 21±+10 vs 28±+13 milliseconds, P=.048, respectively). Similarly, both global and specific vagal measures of HRV were less in the 27 patients with nonsustained ventricular tachycardia on Holter (PNN5O, 7.7±9 vs 15±_13 milliseconds, P=.048, and high frequency component, 19±9 vs 28±+13 milliseconds, P=.05. During follow-up, 10 patients, 9 of whom were aged less than 33 years, experienced catastrophic events; 6 were resuscitated from ventricular fibrillation and 4 died suddenly. Indices of HRV were similar in these 10 patients to indices in the 94 survivors. ConclusionsTime-domain and spectral measures of BRV yield similar information about the specific autonomic influences on the heart. Global and specific vagal influences on HRV were reduced in patients with symptoms and arrhythmias and global HRV is increased in patients with an adverse family history of HCM, but these indices do not add to the predictive accuracy of established risk factors.

Impaired immediate vasoconstrictor responses in patients with recurrent neurally mediated syncope

Immediate responses to head-up tilt were determined in 78 consecutive patients with unexplained syncope undergoing 45-minute tilt tests at 60 degrees. Thirty-four patients developed neurally mediated syncope (mean time to syncope 18 minutes), 40 tolerated the full duration of tilt, and 4 were unable to complete the study but did not develop syncope. Blood pressure, heart rate, forearm blood flow and forearm vascular resistance were measured at baseline and after 2 and 5 minutes of tilt. Syncopal and nonsyncopal patients were well-matched for age and baseline hemodynamic parameters. There was no difference between the groups in heart rate or blood pressure at 2 minutes, but there was a small but significant difference in percent reduction in mean arterial pressure at 5 minutes. After 2 and 5 minutes of tilt, mean forearm blood flow was 2.4 and 2.6 ml/min/100 ml, respectively, in syncopal patients compared with 1.6 (p < 0.05) and 1.7 ml/min/100 ml (p < 0.01), respectively, in patients who tolerated 45 minutes of tilt. In syncopal patients, forearm vascular resistance was 51.0 and 44.0 at 2 and 5 minutes, respectively, whereas in nonsyncopal patients, it was 82.4 (p < 0.02) and 73.1 (p < 0.001), respectively. These differences remained consistent when only data for patients developing syncope after > 15 minutes were included in the analysis. Patients with neurally mediated syncope have clearly demonstrable abnormalities in vascular control immediately after assumption of the upright posture. The results shed new light on the pathophysiology of neurally mediated syncope.

Assessment of autonomic function in patients with neurally mediated syncope: Augmented cardiopulmonary baroreceptor responses to graded orthostatic stress

OBJECTIVESnThe purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tilt-induced neurally mediated syncope.nnnBACKGROUNDnThe causes of individual susceptibility to orthostatic stress leading to recurrent neurally mediated syncope remain obscure. The trigger for sympathetic withdrawal and increased vagal activity is believed to be stimulation of ventricular mechanoreceptors.nnnMETHODSnSeventeen patients (mean age 50.6 years) with recurrent syncope and a positive response on a 45-min 60 degrees head-up tilt test were compared with a control group of 17 patients (mean age 47.5 years) with unexplained syncope and negative tilt test findings. Vagal activity was assessed by high pressure baroreceptor testing and by temporal and spectral analysis of heart rate variability during Holter ambulatory electrocardiographic monitoring. Cardiopulmonary baroreceptor sensitivity was assessed by measurement of forearm vascular responses to lower body negative pressure.nnnRESULTSnMean high pressure baroreceptor sensitivity was 16.4 +/- 12.2 ms/mm Hg in the group with a positive tilt test response compared with 15.1 +/- 13.0 ms/mm Hg in the control group (p = NS). There were no significant differences between the groups in any of the temporal or spectral measures of heart rate variability. The increase in forearm vascular resistance in response to lower body negative pressure was 11.5 +/- 14.2 U in patients with tilt-induced syncope and 3.5 +/- 3.2 U in the control group at -5 mm Hg, 16.8 +/- 18.6 U and 4.8 +/- 5.3 U, respectively, at -10 mm Hg and 26.4 +/- 24.3 U and 10.2 +/- 7.8 U, respectively, at -20 mm Hg (p < 0.001).nnnCONCLUSIONSnPatients with tilt-induced neurally mediated syncope have augmented cardiopulmonary baroreceptor responses to orthostatic stress. This finding sheds new light on the etiology of neurally mediated syncope.

Effects of long-term oral magnesium chloride replacement in congestive heart failure secondary to coronary artery disease.

Magnesium deficiency frequently develops in patients with congestive heart failure and may increase susceptibility to lethal arrhythmias and sudden death via multiple pathophysiologic mechanisms. The effects of peroral magnesium supplementation were investigated in a randomized, double-blind, crossover trial involving 21 patients with stable congestive heart failure secondary to coronary artery disease. All were receiving long-term loop diuretics, and had normal renal function, and low or normal serum magnesium concentrations. Subjects alternately received enteric-coated magnesium chloride (15.8 mmol magnesium per day) and placebo for 6 weeks. Magnesium therapy increased serum magnesium from 0.87 +/- 0.07 to 0.92 +/- 0.05 mmol/liter (p < 0.05), serum potassium from 4.0 +/- 0.3 to 4.3 +/- 0.4 mmol/liter (p < 0.01) and urinary magnesium excretion from 2.82 +/- 0.96 to 4.74 +/- 2.38 mmol/24 hours (p = 0.001). There was no significant change in heart rate or Doppler cardiac index, but mean arterial pressure decreased from 91 +/- 10 to 87 +/- 10 mm Hg (p < 0.05) and systemic vascular resistance from 1,698 +/- 367 to 1,613 +/- 331 dynes s cm-5 (p = 0.047). The frequency of isolated ventricular premature complexes was reduced by 23% (95% confidence interval [CI] 6 to 37%; p < 0.02), couplets by 52% (95% CI 30 to 65%; p < 0.001) and nonsustained ventricular tachycardia episodes by 24% (95% CI 15 to 49%; p < 0.01). Plasma epinephrine decreased from 447 +/- 535 to 184 +/- 106 pg/ml (p = 0.02), but there was no corresponding change in plasma norepinephrine or heart rate variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy.

BackgroundElevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure. Methods and ResultsUsing two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n=21) and compared it with sodium nitroprusside (n= 18). Patients received 30percnt; oxygen via face mask throughout the study. Adenosine at 100 μg/kg/min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41±6% versus 42±4%) and a greater and more consistent fall in transpulmonary pressure gradient (35±6% versus 9±30%, p<0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 ±0.09 to 1.89±0.161. m −2, p<0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7±2.5 to 33.4±3.4 mm Hg, p<0.05). Renal blood flow was unchanged during adenosine infusion. ConclusionsAdenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation.

Atrioventricular Wenckebach Point and Progression to Atrioventricular Block in Sinoatrial Disease.

HAYWOOD, G.A., ET AL.: Atrioventricular Wenckebach Point and Progression to Atrioventricular Block in Sinoatrial Disease. The value of measurement of the atrioventricular (AV) Wenckebach point at rest as a predictor of progression to AV block was investigated prospectively. Twenty‐four patients with sinoatrial disease without evidence of conduction disturbance on 12‐lead ECG or 24‐hour ambulatory monitoring were paced with Medtronic Activitrax II, Medtronic Legend, or Telectronics Meta MV systems in AAI or AAIR modes. Patients were monitored for symptoms and evidence of AV block on 24‐hour tapes. The mean age of the patients was 67 years (range: 42–88). There were 11 males and 13 females. The mean follow‐up time was 10.7 ± 5 months. Four patients required revision of pacing system as a result of development of AV block during follow‐up. One other patient manifested intermittent second degree AV block and remains in AAI. The AV Wenckebach points measured at 1 month post implantation in the four patients who developed AV block requiring revision of system were 140, 125, 165, and 60 (mean 123 ± 4). The mean AV Wenckebach point at first assessment in the remaining 20 patients was 153 ± 24. The mean age of those requiring revision of system was 71 ± 7 compared with 67 ± 14 in those who did not. In this small series the frequency of development of significant AV block was 17%. This is markedly higher than in other recently reported series. The study demonstrates that an AV Wenckebach point above 120/min does not confer immunity from progression to AV block.

Day Case Permanent Pacing

We have previously reported our preliminary experience of day‐case permanent pacing in the United Kingdom. The study has now been extended to 50 patients with follow‐up of 22 ± 4 months. During the study period, all patients referred for permanent pacing, either to the senior author, or as in‐hospital transfers, were considered for the study. Forty two percent of patients considered fulfilled inclusion and exclusion criteria, resulting in a total of 50 patients being randomized either to day case or conventional in‐patient management. In the first month postimplantation, one patient in each group developed a complication requiring revision of system. Only one further pacing related complication occurred over the follow‐up period, percutaneous extrusion of a fixation sleeve with spontaneously healing of the wound. This was in a day‐case patient. Mean duration of in‐patient stay was 5.7 hours in day‐case patients, compared with 70.0 hours in those managed conventionally. Postimplantation local physician consultation rates were equal in both groups. Questionnaires were used to determine the relative acceptability to patients of the two management protocols; on a ten point score of acceptability, the mean score for both groups was 8.8. The difference in cost per patient using day‐case management was approximately £430 (

Anomalous origins of left anterior descending and circumflex coronary arteries from separate orifices in the right coronary sinus

817). We conclude that day‐case permanent pacing in the United Kingdom is feasible, acceptable to patients, and has considerable economic benefits.

The role of ACE inhibitors in the treatment of arrhythmias

A case is described of a 69-year-old man with angina pectoris who was found at coronary angiography to have all three coronary arteries arising by separate orifices from the right coronary sinus. This appears to be a previously unreported anomaly. The embryological origin and mechanisms of angina in coronary arterial anomalies are discussed.