H. L. Thomson

Diastolic ventricular interaction in chronic heart failure

BACKGROUND Diastolic ventricular interaction describes a situation in which the volume of one ventricle is directly influenced by the volume of the other ventricle. Such interaction is normally negligible, but it is accentuated in circumstances associated with pulmonary hypertension and volume overload. When this interaction occurs, acute volume unloading results in a reduction in right ventricular end-diastolic volume, as expected, but left ventricular end-diastolic volume paradoxically increases. Since chronic heart failure is a volume-overloaded state associated with pulmonary hypertension, we hypothesised that this interaction may be clinically important in patients with heart failure. METHODS A radionuclide technique incorporating cardiac scintigraphy was used to measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body suction, on right and left ventricular end-diastolic volumes in 21 patients with chronic heart failure and 12 healthy individuals (controls). FINDINGS In nine heart-failure patients, there was a paradoxical increase in left ventricular end-diastolic volume in association with an expected decrease in right ventricular end-diastolic volume during lower-body suction. This response was not seen in the control group. The mean change in left ventricular end-diastolic volume differed significantly between the heart-failure patients and controls (6 [SD 19] vs -19 [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients who increased left ventricular end-diastolic volume during lower-body suction had higher resting pulmonary arterial and pulmonary capillary wedge pressures than the remaining heart-failure patients. INTERPRETATION The response of nine patients in our study suggests diastolic ventricular interaction, which we believe could be common in patients with chronic heart failure. This finding is relevant to their management, since it emphasises the importance of venodilator therapy. The relation between stroke volume and left ventricular end-diastolic volume, by the Frank-Starting law of the heart, may explain why some patients with chronic heart failure paradoxically increase stroke volume when pulmonary capillary wedge pressure is lowered with vasodilators.

Exercise Capacity in Hypertrophic Cardiomyopathy Role of Stroke Volume Limitation, Heart Rate, and Diastolic Filling Characteristics

BACKGROUND We previously showed that exercise capacity in patients with hypertrophic cardiomyopathy (HCM) is related to peak exercise cardiac output. Cardiac output augmentation during exercise is normally dependent on heart rate (HR) response and stroke volume (SV) augmentation by increased left ventricular end-diastolic volume and/or increased contractility. We hypothesized that in contrast to normal subjects, peak exercise capacity in patients with HCM is determined by the diastolic filling characteristics of the left ventricle during exercise, which would in turn determine the degree to which SV is augmented, and that HR is a relatively unimportant determinant of peak exercise capacity. METHODS AND RESULTS Twenty-three patients with HCM underwent invasive hemodynamic evaluation and measurement of maximal oxygen consumption (VO2max) during erect treadmill exercise to assess the relative importance of changes in HR and SV in determining exercise capacity. Hemodynamic responses to erect and supine exercise were compared in 10 of these patients. In a separate group of 46 patients with HCM, the relation between VO2max and exercise diastolic filling indexes was assessed. Peak HR during erect exercise was 92 +/- 8% of predicted maximum. VO2max was 29.0 +/- 6.4 mL.kg-1.min-1 and was related significantly to peak exercise cardiac index and SV index (r = .71, P < .001 and r = .66, P = .001, respectively) but not to peak HR, HR deficit, or resting or peak pulmonary capillary wedge pressure. Peak cardiac output during erect exercise was not related to peak HR (r = .13, P = NS). When erect and supine exercise were compared, peak HR was lower in the supine position (153.3 +/- 19.9 beats per minute supine versus 172.0 +/- 17.6 beats per minute erect, P = .003), but peak exercise cardiac index was similar (7.9 +/- 2.6 L.min-1.m-2 supine versus 7.5 +/- 2.8 L.min-1.m-2 erect). Pulmonary capillary wedge pressure was higher at rest in the supine versus erect position (15.3 +/- 5.2 versus 8.1 +/- 6.1 mm Hg) but was not significantly higher at peak exercise in the supine versus erect position (28.5 +/- 8 versus 22.4 +/- 11.6 mm Hg erect, P = NS). In the separate group of 46 patients with HCM, VO2max was significantly inversely related to time to peak filling at peak exercise (r = -.60, P < .0001) but did not correlate with time to peak filling at rest, resting ejection fraction, peak filling rate, or peak exercise peak filling rate. CONCLUSIONS SV is the major determinant of peak exercise capacity in the erect position in patients with hypertrophic cardiomyopathy. This in turn is determined by the exercise left ventricular diastolic filling characteristics. HR augmentation does not appear to be a major determinant of peak cardiac output in the erect position.

Baroreflex Sensitivity in Patients With Vasovagal Syncope

BACKGROUND In the present study, we tested the hypothesis that baroreflex sensitivity is reduced in patients with vasovagal syncope compared with normal control subjects. METHODS AND RESULTS We investigated 30 patients with vasovagal syncope (mean age, 43.6 +/- 16.7 years; 14 men and 16 women) and 32 normal control subjects (mean age, 41.8 +/- 17.0 years; 24 men and 8 women). Cardiopulmonary baroreceptor sensitivity was assessed by measuring the change in forearm vascular resistance during subhypotensive lower body negative pressure (LBNP). Carotid baroreflex sensitivity was assessed by measuring the change in RR interval during the manipulation of carotid transmural pressure. Phenylephrine baroreceptor sensitivity was assessed on the basis of the linear regression slope of the RR interval versus systolic blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. In patients with vasovagal syncope, during the application of -10 mm Hg LBNP, forearm vascular resistance decreased by 0.7 +/- 11.6 U versus an increase of 8.3 +/- 6.2 U in control subjects (P = .002). Phenylephrine baroreceptor sensitivity was 11 +/- 7 ms/mm Hg in patients versus 14 +/- 6 ms/mm Hg in control subjects (P = NS). Carotid baroreflex sensitivity was 4 +/- 6 versus 4 +/- 2 ms/mm Hg in patients and control subjects, respectively (P = NS). CONCLUSIONS In patients with vasovagal syncope, during the application of subhypotensive LBNP, there is impaired forearm vasoconstriction or paradoxical forearm vasodilation. This suggests impaired cardiopulmonary baroreceptor inactivation or paradoxical activation of these receptors and is consistent with reduced cardiopulmonary baroreceptor sensitivity.

Failure of Reflex Venoconstriction During Exercise in Patients With Vasovagal Syncope

BACKGROUND In this study, we tested two hypotheses. First, we tested the hypothesis that reflex constriction of the venous capacitance beds in patients with vasovagal syncope is impaired during both subhypotensive lower-body negative pressure. Second, we proposed that splenic venoconstriction may be impaired during exercise in patients with vasovagal syncope. METHODS AND RESULTS We evaluated 25 patients with vasovagal syncope (age, 45.0 +/- 15.9 years; 12 men, 13 women) and 24 control subjects (age, 41.3 +/- 13.7 years; 16 men, 8 women). A nuclear technique was used to assess changes in forearm venous tone during lower-body negative pressure and in splenic venous volume during cycle exercise. Changes in forearm vascular resistance (FVR) during cycle exercise were assessed with a strain-gauge plethysmography technique. The percentage reduction in unstressed forearm vascular volume during lower-body negative pressure was similar in patients and control subjects (9.0 +/- 8.0% versus 9.7 +/- 5.9%, P=NS). During exercise, splenic venous volume decreased less in patients than in control subjects (15.8 +/- 21.7% versus 42.6 +/- 12.6%, P < .0001). FVR decreased by 2 +/- 32% in patients but increased 108 +/- 90% in control subjects (P < .0001). There was no relation between percentage change in splenic volume and percentage change in FVR during exercise in either patients or control subjects (r= -.06, P=NS and r= -.18, P=NS, respectively). CONCLUSIONS Patients with vasovagal syncope exhibit a failure of the normal increase in tone in the splenic capacitance bed and in forearm resistance vessels during dynamic exercise. Forearm venous tone increases normally during lower-body negative pressure.

Diastolic Ventricular Interaction: A Possible Mechanism for Abnormal Vascular Responses During Volume Unloading in Heart Failure

BACKGROUND Baroreflex dysfunction is common in chronic heart failure and contributes to the associated sympathoexcitation. Baroreceptor activity normally decreases during volume unloading, causing an increase in sympathetic outflow and resulting in forearm vasoconstriction. Some heart failure patients develop attenuated vasoconstriction or paradoxical vasodilation. The mechanism for this is unknown. We have recently demonstrated diastolic ventricular interaction in some patients with chronic heart failure as evidenced by increases in left ventricular (LV) end-diastolic volume in association with decreases in right ventricular (RV) volume during volume unloading. We reasoned that such an increase in LV volume, by increasing LV mechanoreceptor activity, would decrease sympathetic outflow and could therefore explain the abnormal vascular responses seen in such patients. METHODS AND RESULTS We assessed changes in forearm vascular resistance (FVR) during application of -20 and -30 mm Hg lower-body negative pressure (LBNP) in 24 patients with chronic heart failure and 16 control subjects. Changes in LV and RV end-diastolic volumes were assessed during -30 mm Hg LBNP in all heart failure patients. Diastolic ventricular interaction was demonstrated in 12 patients as evidenced by increases in LV end-diastolic volume in association with decreases in RV end-diastolic volume during LBNP. Changes in FVR during LBNP (-20 and -30 mm Hg) were markedly attenuated in these 12 patients (-1.6+/-11.2 and -0.9+/-12.5 U) compared with both the remaining patients (11.9+/-10.0 and 17.0+/-12.3 U) and the control subjects (16.5+/-9.5 and 23.1+/-13.9 U) (P<.01 for both comparisons at each level of LBNP). FVR decreased in 5 of these 12 patients during -30 mm Hg LBNP, a response seen in none of the remaining patients (P=.01). CONCLUSIONS Diastolic ventricular interaction in patients with chronic heart failure is associated with attenuated forearm vasoconstriction or paradoxical vasodilation during LBNP. This may explain the apparent derangement in baroreflex control of sympathetic outflow during acute volume unloading in heart failure.

Abnormal Forearm Vascular Responses During Dynamic Leg Exercise in Patients With Vasovagal Syncope

BACKGROUND We have reported previously that in some patients with normal hearts who present with exercise syncope, abnormal forearm vasodilation is seen during leg exercise and tilt table tests are positive. This suggests that exercise syncope may be a variant of vasovagal syncope. In this study we tested the hypothesis that there is loss of the normal forearm vasoconstrictor response during dynamic leg exercise in an unselected population of patients with classic vasovagal syncope. METHODS AND RESULTS We evaluated forearm vascular responses during maximal semierect cycle exercise in 28 consecutive patients with vasovagal syncope and compared them with 30 age-matched control subjects. We also evaluated blood pressure responses during erect treadmill exercise (Bruce protocol). While forearm vascular resistance at rest was similar in the patients with vasovagal syncope and the control group, forearm vascular resistance was markedly lower in the patients than in control subjects at peak exercise (85 +/- 54 versus 149 +/- 94 units, P = .002). Forearm vascular resistance fell by 3 +/- 48% during exercise in patients versus an increase of 135 +/- 103% in control subjects (P < .0001). Systolic blood pressure during erect exercise was lower in patients versus control subjects (155 +/- 32 versus 188 +/- 17 mm Hg, P < .0001). Six of the vasovagal patients complained of exercise syncope or presyncope on specific inquiry, and 4 of these 6 exhibited exercise hypotension during erect treadmill exercise testing. CONCLUSIONS Patients with vasovagal syncope exhibit a failure of the normal vasoconstrictor response in the forearm during dynamic leg exercise. Exercise syncope and presyncope are not uncommon in unselected patients with classic vasovagal syncope, as is exercise hypotension.

Restrictive Left Ventricular Filling Patterns Are Predictive of Diastolic Ventricular Interaction in Chronic Heart Failure

OBJECTIVES The purpose of this study was to determine whether restrictive left ventricular (LV) filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. BACKGROUND We recently demonstrated a diastolic ventricular interaction in approximately 50% of a series of patients with chronic heart failure, as evidenced by paradoxic increases in LV end-diastolic volume despite reductions in right ventricular end-diastolic volume during volume unloading achieved by lower body negative pressure (LBNP). We reasoned that such an interaction would impede LV filling in mid and late diastole, but would be minimal in early diastole, resulting in a restrictive LV filling pattern. METHODS Transmitral flow was assessed using pulsed wave Doppler echocardiography in 30 patients with chronic heart failure and an LV ejection fraction < or = 35%. Peak early (E) and atrial (A) filling velocities and E wave deceleration time were measured. Left ventricular end-diastolic volume was measured using radionuclide ventriculography before and during -30-mm Hg LBNP. RESULTS Nine of the 11 patients with and 2 of the 16 patients without restrictive LV filling patterns (E/A > 2 or E/A 1 to 2 and E wave deceleration time < or = 140 ms) increased LV end-diastolic volume during LBNP (p = 0.001). The change in LV end-diastolic volume during LBNP was correlated with the baseline A wave velocity (r = -0.52, p = 0.005) and E/A ratio (r = 0.50, p = 0.01). CONCLUSIONS Restrictive LV filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. Volume unloading in the setting of diastolic ventricular interaction allows for increased LV filling. Identifying patients with chronic heart failure and restrictive filling patterns may therefore indicate a group likely to benefit from additional vasodilator therapy.

Reduced Cardiopulmonary Baroreflex Sensitivity in Patients With Hypertrophic Cardiomyopathy

OBJECTIVES We sought to assess baroreflex function in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND We have previously demonstrated a specific abnormality in the afferent limb of the cardiopulmonary baroreflex in patients with vasovagal syncope. Patients with HCM exhibit abnormal control of their vasculature during exercise and upright tilt; we therefore hypothesize a similar abnormality in the afferent limb of the cardiopulmonary baroreflex arc. METHODS We investigated 29 patients with HCM and 32 control subjects. Integrated baroreceptor sensitivity was assessed after administration of phenylephrine. Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid artery baroreflex sensitivity was assessed by measuring the in RR interval during manipulation of carotid artery transmural pressure. The integrity of the efferent limb of the reflex arc was determined by studying responses to both handgrip and peripheral alpha-receptor sensitivity. RESULTS During LBNP, FVR increased by only 2.36+/-9 U in patients, compared with an increase of 123+/-8.76 U in control subjects (p=0.001). FVR paradoxically fell in eight patients, but in none of the control subjects. Furthermore, FVR fell by 4.9+/-5.6 U in patients with a history of syncope, compared with an increase of 4.7+/-7.2 U in those without syncope (p=0.014). Integrated and carotid artery baroreflex sensitivities were similar in patients and control subjects (14+/-7 vs. 14+/-6 ms/mm Hg, p=NS and -3+/-2 vs. -4+/-2 ms/mm Hg, p=NS, respectively). Similarly, handgrip responses and the dose/response ratio to phenylephrine were not significantly different. CONCLUSIONS This study suggests that patients with HCM have a defect in the afferent limb of the cardiopulmonary reflex arc.

Mechanism of exercise hypotension in patients with ischemic heart disease. Role of neurocardiogenically mediated vasodilation.

BackgroundExercise-induced hypotension in patients with coronary artery disease (CAD) has been considered to be due to an inability to achieve an adequate increase in cardiac output to match the demands of exercise. We investigated 10 consecutive patients (9 men and 1 woman; age, 38 to 71 years; mean, 52 years) with angiographically documented CAD and exercise-induced hypotension (EIH) (BPPeak < BPRest). Ten approximately age- and sex-matched patients with documented CAD and normal exercise blood pressure response (NBP) served as control subjects. Methods and ResultsNine patients with EIH and all 10 control subjects underwent forearm plethysmography and radionuclide ventriculography (RNV) during semierect cycle exercise. Forearm vascular resistance (FVR) fell by 35 ± 21% in exercise-induced hypotension patients versus an increase of 78 ± 65% in patients with an NBP response (P < .0001). Left ventricular ejection fraction increased by 5.1 ± 7.5% in the group with EIH versus a fall of 4.1 ± 6.2% in the control group (P = .004). Cardiac output at peak exercise (RNV) increased by 2.2 ± 0.89-fold in the group with EIH versus 1.49 ± 0.47-fold in the control group (P = .04). The tenth patient in the group with EIH underwent invasive hemodynamic evaluation during erect exercise. Systolic blood pressure fell (136/80Rest to 50/40Peak) and cardiac output (Fick) tripled, whereas calculated systemic vascular resistance decreased by a factor of 10. Successful angioplasty to an isolated circumflex lesion resulted in resolution of symptoms and abnormal hemodynamic responses during exercise. ConclusionsAbnormal vasodilation associated with a normal or even increased rather than decreased cardiac output response appears to be an important mechanism underlying EIH in some patients with CAD. In the present study, this appears to have been the dominant mechanism in 8 and contributory in 2 of the consecutive patients studied.

Diastolic ventricular interaction in chronic heart failure: Relation to heart rate variability and neurohumoral status

SummaryIt is likely that abnormal baroreflex control mechanisms are at least partially responsible for autonomic dysfunction in chronic heart failure. We recently demonstrated that diastolic ventricular interaction is associated with impaired baroreflex control of vascular resistance in heart failure. We reasoned that by con-straining left ventricular filling, such interaction would decrease baroreflex activity and, thereby, increase sympathetic and decrease parasympathetic outflow. Wehypothesized, therefore, that diastolic ventricular interaction in chronic heart failure patients would be associated with autonomic dysfunction.We used radionuclide ventriculography to measure changes in left and right ventricular end-diastolic volumes during acute volume unloading achieved by—30 mm Hg lower-body negative pressure in 30 patients with chronic heart failure. An increase in left ventricular volume in association with a reduction in right ventricular volume indicates diastolic ventricular interaction (a larger increase indicating a greater degree of interaction). We also measured heart rate variability (n = 23) and resting venous plasma norepinephrine (n = 24), epinephrine (n = 24), and atrial natriuretic peptide (ANP) (n = 14).During lower-body negative pressure, while right ventricular volume decreased in all patients (P < 0.001), left ventricular end-diastolic volume increased (from 152 ± 25 to 157 ± 36ml/m2, P = 0.01). The change in left ventricular volume was positively correlated with resting plasma norepinephrine (P < 0.01) and ANP (P <0.005), and negatively correlated with the standard deviation of normal to normal R-R intervals (P <0.005), the root-mean-square of differences between successive normal to normal R-R intervals (P < 0.05), total power (P < 0.01), low-frequency power (P < 0.01), and high-frequency power (P < 0.05).Diastolic ventricular interaction in patients with chronic heart failure is associated with sympathetic nervous system activation evidenced by increased plasma norepinephrine and reduced heart rate variability.