Peter J. Counihan

Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy.

To investigate the incidence of abnormal exercise blood pressure responses in hypertrophic cardiomyopathy (HCM) and the potential role of hemodynamic instability as a mechanism of sudden death, 129 consecutive patients with HCM underwent maximal symptom-limited treadmill exercise testing with blood pressure recording. Four patterns of blood pressure response were observed. Forty-three patients had significant exercise hypotension, with either a continuous fall in systolic blood pressure (n = 5) from the start of exercise or a sudden fall in systolic blood pressure (20-100 mm Hg; mean, 40 mm Hg) from the peak value (n = 38), 23 patients had a normal response during exercise but an abnormal blood pressure response in the recovery period, and the remaining 62 patients demonstrated a normal blood pressure response. Patients with exercise hypotension were younger (33 +/- 14 versus 46 +/- 14 years) and more of them had a family history of HCM and sudden death compared with those with a normal blood pressure response (15 of 43 versus 6 of 62 patients). Similarly, the 23 patients with abnormal recovery blood pressure responses were younger (43 +/- 16 versus 46 +/- 14 years) and had a higher incidence of a family history of sudden death (10 of 24 versus 6 of 62 patients). Left ventricular cavity dimensions were smaller in those with exercise hypotension, but 11 other clinical, echocardiographic, and arrhythmic variables were similar. To assess the mechanism of exercise hypotension, 14 patients who demonstrated exercise hypotension and 14 symptomatic patients with a normal exercise blood pressure response underwent invasive hemodynamic exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy.

BackgroundExercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. Methods and ResultsTo enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 ± 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 ± 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 ± 13 versus 46 ± 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n =6) or an abrupt decrease in systolic blood pressure (20–60 mm Hg) from the peak value (n =32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p < 0.001). ConclusionsThe relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy.

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.

Signal-averaged electrocardiography in hypertrophic cardiomyopathy

A major goal in the management of patients with hypertrophic cardiomyopathy is the prediction of sudden death. To evaluate the high gain signal-averaged electrocardiogram (ECG) in this setting, 64 patients with hypertrophic cardiomyopathy and 50 age- and gender-matched control subjects were studied. An abnormal signal-averaged ECG was more common in patients than in control subjects: 13 (20%) of 64 patients with hypertrophic cardiomyopathy had abnormalities compared with 2 (4%) of the 50 control subjects (p less than 0.001). There was a significant association between the presence of nonsustained ventricular tachycardia on 48 h ECG Holter monitoring and the presence of an abnormal signal-averaged ECG: 8 (47%) of the 17 patients with nonsustained ventricular tachycardia and 6 (86%) of 7 patients with more than three episodes of nonsustained ventricular tachycardia per 24 h had signal-averaged ECG abnormalities. There was no association between an abnormal signal-averaged ECG and a family history of premature sudden cardiac death, a history of syncope, symptomatic status, maximal left ventricular wall thickness, the presence of systolic anterior motion of the mitral valve or maximal rate of oxygen uptake on exercise. However, of four patients with a history of cardiac arrest, three had an abnormal signal-averaged ECG. Sensitivity was 50%; specificity was 93% and positive predictive accuracy was 77% for the signal-averaged ECG in detecting patients with electrical instability (defined as a history of cardiac arrest or the presence of nonsustained ventricular tachycardia, or both).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

DETERMINANTS OF EXERCISE CAPACITY IN HYPERTROPHIC CARDIOMYOPATHY

Exercise capacity in hypertrophic cardiomyopathy is thought to relate to elevated left atrial pressure as a consequence of impaired diastolic function, but this assumption has not previously been evaluated. Twenty-three patients with hypertrophic cardiomyopathy underwent hemodynamic assessment during symptom-limited maximal exercise with objective measurement of exercise capacity by respiratory gas analysis. Maximal oxygen consumption and anaerobic threshold were 28.1 +/- 7.5 and 21.5 +/- 6.1 ml/kg per min, respectively (the lower limit of reference range in our laboratory is 39 and 27 ml/kg per min, respectively). Maximal oxygen consumption was reduced in 11 of 13 patients who were in New York Heart Association functional class I and who denied limitation of exercise capacity and in all 10 patients who were in functional class II or III. Maximal oxygen consumption and anaerobic threshold were related to peak cardiac index (r = 0.650, p less than 0.001 and r = 0.459, p = 0.03, respectively) and to the increase in cardiac index on exercise (r = 0.677, p less than 0.001 and r = 0.509, p = 0.016, respectively), but not to cardiac index at rest, peak and rest pulmonary capillary wedge pressure, pulmonary capillary wedge pressure at an oxygen consumption of 15 ml/kg per min or the rise in pulmonary capillary wedge pressure on exercise. These findings are not consistent with the hypothesis that elevated left atrial pressure is the major determinant of exercise capacity in patients with hypertrophic cardiomyopathy and they suggest that, as in patients with chronic cardiac failure, other mechanisms should be considered.

Regional thallium-201 washout and myocardial hypertrophy in hypertrophic cardiomyopathy and its relation to exertional chest pain

The mechanism of exertional chest pain in hypertrophic cardiomyopathy is uncertain, but may relate to myocardial ischemia. To study the mechanism of exertional chest pain in hypertrophic cardiomyopathy, dipyridamole-stress thallium-201 single-photon emission computed tomography was performed in 82 consecutive patients, and the 3-hour washout of thallium in relation to the tomographic image, regional wall thickness on echocardiography, and other clinical findings was analyzed. There was a weak inverse correlation of regional washout and wall thickness in 298 analyzed quadrant areas (r = -0.29; p = 0.0001). Twenty-five patients (31%) had history of exertional chest pain, and showed a significantly lower total washout and greater maximal left ventricular wall thickness than did those without chest pain (32 +/- 10% vs 37 +/- 9% [p = 0.03], and 27 +/- 7 vs 23 +/- 7 mm [p = 0.03], respectively). Even in mildly and nonhypertrophied areas, patients with chest pain had a significantly lower regional washout than did those without pain (33 +/- 10% vs 38 +/- 9%; p = 0.02), despite similar left ventricular wall thickness (12 +/- 2 vs 11 +/- 3 mm; p = NS). Reduced washout was strongly associated with exertional chest pain and was observed in myocardial regions that had normal as well as increased thickness, which indicates that this abnormality of thallium kinetics is a function of the disease process and not the magnitude of left ventricular hypertrophy.

Risk-Benefit Assessment of Amiodarone in the Treatment of Cardiac Arrhythmias

SummaryCardiac arrhythmias are a cause of significant morbidity and mortality in patients with cardiac disease, and thus represent a major management problem. The recognition that antiarrhythmic drugs have the potential to aggravate as well as to attenuate arrhythmias has prompted clinicians to reconsider treatment strategies and weigh the benefits of treatment against the risks. In this context, amiodarone has emerged as an effective antiarrhythmic agent and when used at the lowest effective dose has an acceptable side effect profile. This review focuses on the current clinical usage of amiodarone in a broad variety of cardiac arrhythmias, and addresses the risk-benefits arising from its use. It further discusses the current position of amiodarone in the management of sudden cardiac death.

Low-dose amiodarone for the treatment of arrhythmias in hypertrophic cardiomyopathy.

H ypertrophic cardiomyopathy is characterised by an inappropriate and unexplained hypertrophy of the ventricular myocardium. The natural history of this condition is one of progressive symptomatic deterioration over many years with a high incidence of sudden death.” The risk of sudden death is greatest in children and young adults with an annual mortality of approximately 6%. In adults the incidence of sudden death declines but remains significant at 2.5%.” This high incidence of sudden death affecting a relatively young population who have a seemingly benign condition emphasises the importance of identifying those patients at greatest risk of sudden death. It is in the management of this group that amiodarone has its greatest potential impact.