Dataset Information

Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy.

ABSTRACT:

Background

Left ventricular outflow tract obstruction is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). The classical quantification of intraventricular obstruction is performed in resting conditions in supine position, but this assessment does not reflect what happens in HCM patients (pts) in their daily activities, neither during effort nor during orthostatic recovery.

Aim

To assess intraventricular gradients with echocardiography during treadmill exercise and in the recovery period in upright position, in HCM pts.

Methods

We studied 17 HCM pts (9 males, mean age 53 +/- 16 years, 11 with obstructive HCM). Each pt had 2 echocardiographic evaluations at rest (left lateral decubitus (LLD) and orthostatic position). The pts then underwent a treadmill exercise test and intraventricular gradients were measured at peak exercise and during recovery in orthostatic position.

Results

3 pts with non-obstructive HCM at rest developed intraventricular gradients during exercise. 1 pt developed this gradient only during orthostatic recovery. The mean intraventricular gradient in LLD was 49 +/- 24 mmHg; in orthostatic position was 62 +/- 29 mmHg (p < 0.001 versus in LLD); at peak exercise was 83 +/- 35 mmHg (p < 0.001 versus supine rest); during recovery it was 96 +/- 35 mmHg (p < 0.001 versus peak exercise)

Conclusion

In HCM pts the intraventricular gradient increases in orthostatic position, increases significantly during treadmill exercise and continues increasing in the recovery period in orthostatic position. This type of evaluation can help us to better understand the physiopathology, the symptoms and the efficacy of different therapeutic modalities in this disease and should be routinely used in the assessment of HCM pts.

SUBMITTER: Miranda R

PROVIDER: S-EPMC2413212 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Publications

Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy.

Miranda Rita R Cotrim Carlos C Cotrim Carlos C Cardim Nuno N Almeida Sofia S Lopes Luís L Loureiro Maria José MJ Simões Otília O Cordeiro Pedro P Fazendas Paula P João Isabel I Carrageta Manuel M

Cardiovascular ultrasound 20080515

<h4>Background</h4>Left ventricular outflow tract obstruction is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). The classical quantification of intraventricular obstruction is performed in resting conditions in supine position, but this assessment does not reflect what happens in HCM patients (pts) in their daily activities, neither during effort nor during orthostatic recovery.<h4>Aim</h4>To assess intraventricular gradients with echocardiography during treadm ...[more]

PMID: 18482456

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Project description:Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.

Project description:BACKGROUND:Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations. METHODS:The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSVincl) or exclusion (LVSVexcl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvolAoi or MRvolAoe) or MPA (MRvolMPAi or MRvolMPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings. RESULTS:MRvolAoi was higher than MRvolMPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR)?=?31.5-60.0 vs. 35.5 ml, IQR?=?26.0-51.0; p <?0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR?=?16.0-32.0 vs. 24.0 ml, IQR?=?15.3-32.0; p?=?0.26) or controls (18.0 ml, IQR?=?14.3-21.8 vs. 20.0 ml, IQR?=?14.3-22.0; p?=?0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvolAoi) was higher than pulmonary-based findings (MRvolMPAi) (bias?=?9.5 ml; limits of agreement: -11.7-30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSVexcl mirrored those derived using LVSVincl. However, MRvol values calculated using LVSVexcl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p???0.0001 for all comparisons). CONCLUSIONS:In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

Project description:BackgroundConventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention.MethodsWe retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions.ResultsThirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan-Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36-29.25, P = 0.02). Five patients experienced ICD implant-related complications.ConclusionsOur findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

Dataset Information

Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy.

Background

Aim

Methods

Results

Conclusion

Publications

Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy.

Similar Datasets

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