James F. Sneddon

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

OBJECTIVES The purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tilt-induced neurally mediated syncope. BACKGROUND The 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. METHODS Seventeen 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. RESULTS Mean 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). CONCLUSIONS Patients 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.

Do patients with neurally mediated syncope have augmented vagal tone

Abstract Head-up tilt testing is now recognized as a valuable diagnostic tool for identifying patients with neurally mediated syncope. However, the causes of individual susceptibility to such orthostatic stress have not been well characterized in this patient population. At the time of syncope, there is evidence to suggest both withdrawal of sympathetic tone as well as increased vagal activity. The latter is manifest by bradycardia, increased high-frequency spectral power of heart rate variability and release of pancreatic polypeptide. 1,2 The purpose of this study was to assess the importance of resting autonomic tone assessed by temporal and spectral measures of heart rate variability and vagal reserve assessed by baroreceptor sensitivity in patients with neurally mediated syncope and in control subjects.

Effect of subcutaneous nicotine injections on EEG alpha frequency in non-smokers: a placebo-controlled pilot study

The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection and 8.5 ng/ml 10 min after the second injection. The nicotine injections produced an increase in mean dominant alpha frequency on the electroencephalogram (EEG) which was 2 Hz greater than the effect of placebo (P=0.049) and also produced a heart-rate boost which was 8 beats per minute greater than that produced by placebo (P=0.022). These effects on dominant alpha frequency and heart rate were most apparent in the 10 min following each nicotine injection. The increase in dominant alpha frequency found in non-smokers in this study was similar to that following nicotine inhalation in abstinent smokers in previous studies, and suggests that this is a primary effect of nicotine, rather than simply a reversal of withdrawal-induced EEG slowing.

Assessment of the diagnostic value of head-up tilt testing in the evaluation of syncope in hypertrophic cardiomyopathy

Abstract Syncope is a common symptom in patients with hypertrophic cardiomyopathy (HC), and in young patients is associated with an increased risk of sudden death. 1,2 The exact pathophysiologic mechanisms resulting in hemodynamic collapse are not fully understood but may involve the interaction of hemodynamic instability, myocardial ischemia and potential arrhythmic substrates. 3 Accurate diagnosis of the cause is frequently difficult and is of the utmost importance if treatment to prevent recurrence or potentially catastrophic events is to be instituted appropriately. In patients with structurally normal hearts, head-up tilt testing has been shown to be a valuable diagnostic tool for the evaluation of unexplained syncope, and 2 recent reports have suggested that this may also be so in patients with HC. 4,5 This study evaluated the usefulness of head-up tilt testing in the management of syncope in patients with HC and compared the results of tilt testing with the blood pressure response to exercise, a marker of hemodynamic instability. 6

Influence of thrombolytic therapy on the evolution of baroreflex sensitivity after myocardial infarction

Depressed baroreceptor sensitivity (BRS) has been associated with an increased risk of ventricular arrhythmias and sudden cardiac death after myocardial infarction, but the influence of thrombolytic therapy on BRS has not been examined. To determine the effect of thrombolytic therapy on the evolution of BRS after myocardial infarction, BRS was assessed at 6 days, 6 weeks, and 3 months in 76 patients, 53 (70%) of whom had received thrombolytic therapy. The mean age (57 vs 57 years), sites of infarction, and the proportion of patients taking beta-blockers (68% vs 52%) did not differ between patients who did and those who did not receive thrombolytic therapy. There was no difference in predischarge mean left ventricular ejection fractions (42% vs 46%) between the two groups of patients, but mean baseline BRS was 9.2 (0.8) msec/mm Hg in patients who were treated with thrombolysis and 5.9 (1.3) msec/mm Hg in those who were not (p = 0.03). At 6 weeks the corresponding values were 9.7 (1.1) and 11.1 (2.8) msec/mm Hg (p = 0.6) and at 3 months 9.1 (1.0) and 6.5 (1.1) msec/mm Hg (p = 0.07). At baseline 13% of patients who were treated with thrombolysis and 13% of those who were not had BRS < 3.0 msec/mm Hg, but at 3 months 9% of patients who were treated with thrombolytic agents compared with 17% of those who had BRS < 3.0 msec/mm Hg. In conclusion, early after myocardial infarction mean BRS was higher in patients treated with thrombolysis compared with nontreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and hemodynamic evaluation of the 19-mm Carpentier-Edwards supraannular aortic valve

The clinical and hemodynamic performance of the 19-mm Carpentier-Edwards supraannular aortic valve is largely unknown compared with that of the larger valves. Over 4 years we implanted the 19-mm Carpentier-Edwards supraannular aortic valve into 21 patients (20 female) with a mean age of 75 +/- 1.2 years (range, 59 to 86 years) and a mean body surface area of 1.6 +/- 0.03 m2 (range, 1.3 to 1.7 m2). There were four deaths, one operative and three late noncardiac deaths. Follow-up of the 17 survivors for a mean of 20 +/- 3.1 months (range, 2 to 42 months) demonstrated symptomatic improvement in all 17 (all are now in New York Heart Association functional class I or II). There were no valve-related complications and no patient required long-term anticoagulation. Doppler echocardiographic studies were used to assess the in vivo hemodynamic profile of the valve. Mean postoperative aortic valve gradient was 34.1 +/- 2.7 mm Hg (range, 19 to 52 mm Hg). Functional valve orifice area was 1.1 +/- 0.09 cm2 (range, 0.6 to 1.8 cm2). Mean cardiac output was 3.92 +/- 0.17 L/min (range, 3.2 to 5.1 L/min) with a mean cardiac index of 2.5 +/- 0.11 L.min-1 x m-2 (range, 2.1 to 3.2 L.min-1 x m-2). In conclusion, we have demonstrated that aortic valve replacement with the 19-mm Carpentier-Edwards supraannular aortic valve has a low operative mortality and offers major clinical benefits despite moderate transprosthetic gradients. This approach provides an alternative management strategy in elderly patients who would otherwise require low-profile mechanical valves or aortic root enlargement.

A prospective study of the efficacy and safety of adjuvant metoprolol and xamoterol in combination with amiodarone for resistant ventricular tachycardia associated with impaired left ventricular function

Combination antiarrhythmic drug therapy may be more effective than treatment with a single agent for control of refractory cases of sustained ventricular tachycardia (VT). In a prospective randomized crossover study of 20 patients with impaired left ventricular function (ejection fraction of 28% +/- 8%) and recurrent VT in spite of treatment with amiodarone, we compared the efficacy and safety of adjuvant therapy with metoprolol, 50 mg two times daily and xamoterol, 200 mg two times daily. Metoprolol caused hemodynamic deterioration in five patients, and only one also experienced intolerance to xamoterol. Sustained VT was inducible in all 20 patients who were receiving amiodarone alone but was suppressed or rendered nonsustained in 8 of 20 patients during treatment with amiodarone plus xamoterol and in 6 of 17 patients during treatment with amiodarone plus metoprolol. Addition of xamoterol restored sinus rhythm in four patients who presented with incessant VT, and metoprolol was effective for three of them. Neither beta-blocker significantly altered tachycardia cycle length or any electrophysiologic parameter other than the slowing of the sinus rate. Both beta-blockers suppressed exercise-induced VT in 3 of 4 patients, and addition of xamoterol significantly increased treadmill exercise duration (7.1 +/- 1.8 min) compared with administration of amiodarone alone (3.8 +/- 1.5 min; p < 0.01). Fourteen patients were discharged with prescriptions for amiodarone-beta-blocker combinations. During a mean follow-up period of 13 months (range, 2 to 24 months), there were three cases of recurrent VT (in all patients VT remained inducible) and no sudden deaths.(ABSTRACT TRUNCATED AT 250 WORDS)