Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements: a prospective, randomly assigned, blinded study.

OBJECTIVES: We sought to assess the impact of contrast injection and harmonic imaging, on the measure by echocardiography of left ventricular (LV) remodeling. BACKGROUND: Left ventricular remodeling is a precursor of LV dysfunction, but the impact of contrast injection and harmonic imaging on the accuracy or reproducibility of echocardiography is unclear. METHODS: We prospectively collected LV images by using simultaneous methods. Then, LV volumes were measured off-line, in blinded manner and in random order. The accuracy of echocardiography was determined in comparison to electron beam computed tomography (EBCT) in 26 patients. The reproducibility of echocardiography was assessed by three blinded observers with different training levels in 32 patients. RESULTS: End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), as measured by EBCT (195 +/- 55, 58 +/- 24 and 137 +/- 35 ml and 71 +/- 5%, respectively) and echocardiography with harmonic imaging and contrast injection (194 +/- 51, 55 +/- 20 and 140 +/- 35 ml and 72 +/- 4%, respectively), showed no differences (all p > 0.15) and excellent correlations (all r > 0.87). In contrast, echocardiography using harmonic imaging without contrast injection underestimated the EBCT results (all p < 0.01). Reproducibility was superior with rather than without contrast injection for intraobserver and interobserver variabilities (all p < 0.001). Values measured by different observers were different without contrast injection, but were similar with contrast injection (all p > 0.18). Consequently, intrinsic patient differences represented a larger and almost exclusive proportion of global variability with contrast injection for EDV (94 vs. 79%), ESV (93 vs. 82%), SV (87 vs. 53%) and EF (84 vs. 41%), as compared with harmonic imaging without contrast injection (all p < 0.005). CONCLUSIONS: For assessment of LV remodeling, echocardiography with harmonic imaging and contrast injection improved the accuracy and reproducibility, as compared with imaging without contrast injection. With contrast injection, variability was almost exclusively due to intrinsic patient differences. Therefore, when evaluation of LV remodeling is deemed important, assessment after contrast injection should be the preferred echocardiographic approach.

Echocardiographic assessment of mitral regurgitation.

Although the natural history of mitral regurgitation (MR) is poorly defined, evidence has been found for excess mortality and morbidity in patients with severe MR who are managed conservatively. With improved mortality and morbidity in the surgical management of this condition, we are becoming increasingly aggressive in offering surgery to patients with severe MR. Surgery may be offered even in the absence of symptoms or left ventricular dysfunction, provided that the valve seems reparable, the patient's MR is severe, and the surgical team is experienced in valve repair. Echocardiography is critically important in determining the feasibility of valve repair and accurately assessing the severity of the patient's MR. It also allows assessment of the effect of MR on the left ventricle and the left atrium.

Timing of surgery in patients with chronic, severe mitral regurgitation.

Patients with severe mitral regurgitation (MR) who are managed conservatively sustain excess mortality and morbidity. With improved mortality and morbidity rates being achieved with surgical management, cardiologists and cardiac surgeons are becoming more aggressive in treating patients with severe MR with surgery. Recent data indicate that even in the absence of symptoms or left ventricular dysfunction, surgery should be offered as a treatment for MR, provided that the regurgitation is severe, the valve seems to be repairable, and the surgeon is experienced in valve repair and is aided by intraoperative transesophageal echocardiography.

The role of diastolic ventricular interaction in abnormal cardiac baroreflex function in chronic heart failure.

Baroreflex abnormalities have been well documented in both patients with chronic heart failure and experimental animal models of heart failure. These abnormalities are associated with increased mortality and probably contribute to neurohumoral activation. While it is likely that several mechanisms contribute to reduced baroreflex sensitivity, it has been difficult to explain why baroreflex control mechanisms during acute volume unloading in patients with severe chronic heart failure should be directionally opposite to those in normal subjects. Volume unloading normally causes a reduction in baroreceptor activity, and hence an increase in sympathetic outflow; however, patients with chronic heart failure develop attenuated increases or paradoxical reductions in forearm vascular resistance, muscle sympathetic nerve activity, and noradrenaline spillover. It has been suggested that this probably represents paradoxical activation of left ventricular (LV) mechanoreceptors, but why LV receptors should behave in such a fashion has not been determined. In the setting of diastolic ventricular interaction, the filling of the left ventricle is constrained by the surrounding pericardium and right ventricle. In these patients, the reduction in right ventricular (RV) volume that normally occurs during acute volume unloading allows for an increase in LV end-diastolic volume (as opposed to the reduction in LV volume that normally occurs). We have demonstrated this to be important in some patients with chronic heart failure, and observed that baroreflex control of forearm vascular resistance was markedly impaired in these patients. We propose that the increase in LV volume that occurred during volume unloading would increase LV mechanoreceptor activity, and could therefore explain the paradoxical reductions in sympathetic outflow. As discussed, this has important therapeutic implications.

Haemodynamics and left ventricular mass regression: a comparison of the stentless, stented and mechanical aortic valve replacement.

OBJECTIVE: Our objective was to compare the degree of change in hemodynamics and left ventricular mass (LVM) regression after aortic valve replacement (AVR) with stentless, stented and mechanical valves. METHODS: Patients greater than 59 years of age had AVR for aortic stenosis with the stentless xenograft (Cryolife-O'Brien, CLOB), stented xenograft (Carpentier-Edwards, C-E) or mechanical valve (ATS). One-hundred and forty-two patients received stentless, 40 stented, and 69 mechanical valves (mean age 74 +/- 6 vs. 72 +/- 7 and 67 +/- 6 years, respectively). Serial echocardiography was performed. RESULTS: The left ventricular outflow tract diameter was similar pre-operatively in the stentless versus the stented versus the mechanical groups (2.2 +/- 0.4 vs. 2.3 +/- 0.2 vs. 2.2 +/- 0.3 cm; P, n.s). The effective orifice area was larger immediately post-operatively in the stentless versus the stented or the mechanical group (2.4 +/- 0.4 vs. 2.0 +/- 0.6 vs. 2.0 +/- 0.7 cm2, P = 0.0001 for both comparisons). The peak aortic gradient at 6 months was significantly less in the stentless versus the stented and mechanical groups (15 +/- 7 vs. 25 +/- 9 vs. 22 +/- 9 mmHg, P < 0.0001). LVM regressed over 6 months in all subgroups: stentless 272 +/- 64 g vs. 220 +/- 72 g, P = 0.0001, stented 257 +/- 58 vs. 230 +/- 74 g, P = 0.02, and mechanical 267 +/- 95 vs. 204 +/- 54 g, P = 0.003. The reduction in LVM was greater in the stentless versus the stented (P = 0.05) but similar to the mechanical group. CONCLUSIONS: AVR with the stentless xenograft results in superior hemodynamics compared to the stented and mechanical valve replacements. AVR in all three groups leads to a significant regression of left ventricular hypertrophy within 6 months. However the reduction in LVM is greater in subjects with stentless and mechanical valves, which may have prognostic significance.

Reflex responses of venous capacitance vessels in patients with hypertrophic cardiomyopathy.

1. The aim of this study was to determine if there is impaired reflex venoconstriction in patients with hypertrophic cardiomyopathy and whether this is related to a history of syncope or exercise hypotension. 2. Thirty percent of patients with hypertrophic cardiomyopathy have exercise-induced hypotension associated with a failure of arteriolar constriction. Impaired venoconstriction could exacerbate this situation. 3. We evaluated 43 patients with hypertrophic cardiomyopathy and 24 controls. Nuclear venous plethysmography was used to measure forearm venous capacitance during lower body negative pressure, splenic venous volume changes during bicycle exercise and blood pressure responses to treadmill exercise. We assessed any association between abnormal reflex venous control and a history of syncope and exercise hypotension. 4. The percentage reduction in unstressed forearm venous volume during lower body negative pressure was similar in patients and controls (8.9 +/- 7.1% versus 9.7 +/- 5.9%, P not significant). Patients with a history of syncope demonstrated a less marked percentage reduction in volume than those without (-2.1 +/- 6.9% versus -10.6 +/- 6.0%, P = 0.001). In three patients with a history of syncope there was a paradoxical increase in forearm venous volume during lower body negative pressure. During exercise there was a substantially smaller decrease in splenic venous volume in patients compared with controls (-20.1 +/- 14.0% and -42.6 +/- 12.6% respectively, P = 0.0001). Furthermore, there was an association between attenuated splenic venoconstriction or venodilation and exercise hypotension in patients (P = 0.005). 5. Abnormal reflex control of venous capacitance beds in patients with hypertrophic cardiomyopathy was associated with both syncope and exercise hypotension.

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.

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.

Transesophageal echocardiography in an operation for pulmonary arteriovenous malformation.

Transesophageal echocardiography has been described as a useful tool in the diagnosis of pulmonary arteriovenous malformations. We describe a case in which intraoperative transesophageal echocardiography was used to aid localization and ensure complete surgical ligation.

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

It 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 constraining left ventricular filling, such interaction would decrease baroreflex activity and, thereby, increase sympathetic and decrease parasympathetic outflow. We hypothesized, 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 +/- 36 ml/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.

Forearm vasoconstriction during dynamic leg exercise in patients with chronic heart failure.

Previous studies assessing vascular responses in nonexercising beds during exercise in patients with chronic heart failure (CHF) have yielded varying results. We proposed that the clinical and hemodynamic severity of heart failure may explain some of the variation. We reasoned that diastolic ventricular interaction (DVI), by limiting the ability of such patients to increase left ventricular (LV) volume and stroke volume during exercise, would attenuate baroreflex activation, resulting in increased sympathetic activation and hence exaggerated vasoconstriction. We hypothesized therefore that vasoconstriction in nonexercising beds would be exaggerated in patients with symptomatic and hemodynamically severe heart failure, particularly if associated with DVI. We measured forearm vascular resistance (FVR) during semierect cycle exercise in 22 CHF patients and 23 control subjects. DVI was assessed by measuring changes in ventricular volumes (radionuclide ventriculography) during volume unloading (-30 mm Hg lower-body negative pressure) in the heart failure patients and was inferred when LV end-diastolic volume paradoxically increased. Patients with symptoms of heart failure developed larger increases in FVR during exercise than did asymptomatic patients. There were significant correlations between the change in FVR during peak exercise and the resting mean pulmonary arterial pressure and pulmonary vascular resistance. CHF patients with DVI developed exaggerated increases in FVR (median [25th to 75th percentile]) compared with the remaining patients during low-workload exercise (138 [66 to 171] vs 6.4 [-4.3 to 28] units, P = 0.002) and during peak exercise (160 [90 to 384] vs 61 [-7.4 to 75] units, P < 0.02). Vasoconstriction in nonexercising beds is exaggerated in CHF patients with clinically and hemodynamically severe heart failure, particularly if associated with DVI. This may explain some of the reported variation in the degree of sympathetic activation that occurs during exercise in CHF patients.

The Cryolife-O'Brien stentless aortic porcine xenograft valve.

BACKGROUND: The advantageous design of the Cryolife-O'Brien stentless porcine aortic valve permits specific quick, easy, supravalvular implantation using single layer continuous 3-0 polypropylene suture. The advantages, contraindications, and implantation errors to avoid are detailed. The use of this valve for aortic valve replacement in the elderly population has been directed to proving its efficacy and establishing its grounds for durability while maintaining all of the advantages of a stentless tissue valve. METHODS: From December 1992 to September 1998, this valve was used in 240 patients (mean age 73 years: 15% > 80 years), 45% receiving associated coronary artery grafting (2.4 grafts per patient). Left ventricular (LV) myomectomy was necessary in 12% of patients. Detailed postoperative follow-up (100%) analysis included 650 serial echocardiographic studies. RESULTS: The 30-day mortality was low at 1.2% (3 deaths of 240 elderly patients). Ten patients had late mortality (1.5 months to 5 years), all nonvalve related. No structural failure and one only explant for endocarditis have occurred. Echocardiographic analyses have shown low mean transvalvular gradients in relationship to time (8.18 mmHg at 18 months) and to valve size (8.52 mmHg for a 23-mm host aortic annulus). Incompetence has been zero or a trace in 97% of the patients at 21/2 years. No patient over the 6 years shows valve deterioration. CONCLUSION: Six years of experience with this stentless valve in 240 elderly patients has revealed the many advantages of this safe, composite, and truly stentless device that is assembled without the need for Dacron support. Excellent sustained hemodynamics with low gradients, minimal regurgitation, and a good effective orifice have been coupled with low immediate mortality, no intrinsic valve failure, and one explant for endocarditis. Marked LV regression and minimal late valve-related complications confirm the safety and advantages of this stentless valve.

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.

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.

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.

Demonstration of late cardiotoxicity following bone marrow transplantation by assessment of exercise diastolic filling characteristics.

We evaluated the role of rest and exercise left ventricular diastolic filling parameters as a marker of cardiotoxicity in 25 consecutive patients 1 year following BMT. Ten age- and sex-matched subjects served as controls. Patients were evaluated in toto and in three sub-groups according to chemotherapy. Left ventricular ejection fraction (EF), peak filling rate (PFR) and time to peak filling (TTPF) were assessed at rest and at peak exercise. EF and PFR were similar at rest and at peak exercise in patients and controls. TTPF was significantly prolonged at rest in patients compared to controls (200 +/- 65 vs 131 +/- 26 ms, P = 0.003) and at peak exercise was markedly longer in patients (142 +/- 40 vs 54 +/- 19 ms, P < 0.001). Sub-group analysis demonstrated abnormal resting TTPF in those patients who had received either combination anthracycline and CY or anthracycline and melphalan, while those patients who received CY alone had normal resting TTPF. However, exercise TTPF was abnormally prolonged in all patient groups. While all controls demonstrated a normal decrease in TTPF during exercise, four of the 25 patients had a paradoxical increase in TTPF during exercise. Exercise diastolic function may provide evidence of cardiotoxicity in long-term survivors of BMT.

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.

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.

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.