Dataset Information

Relationship between baseline resting diastolic function and exercise capacity in patients with hypertrophic cardiomyopathy undergoing treadmill stress echocardiography: a cohort study.

ABSTRACT:

Objective

Diastolic dysfunction (DD) is often incriminated in the symptomatology of patients with hypertrophic cardiomyopathy (HCM), but with limited supporting data. This study sought to assess the relationship between baseline diastolic function and exercise capacity in patients with HCM.

Design

Retrospective study.

Setting

Tertiary referral centre from Cleveland, Ohio, USA.

Participants

695 consecutive patients with a diagnosis of HCM who underwent exercise stress echocardiography between 1996 and 2011.

Primary and secondary outcome measures

Diastolic function was reassessed from the resting echocardiograms by two blinded board-certified cardiologists. Maximal metabolic equivalents (MET) were extracted from the records. Multivariate regression analysis was performed to determine independent predictors of METs achieved.

Results

Of 695 patients, 130 were excluded because of inability to assess diastolic function. There was no significant difference in maximal METs achieved between those excluded and included in the analysis (p=0.80). There were 495 remaining patients with a mean age (SD) of 50 (15) years, and 32% women among whom 102 (21%) had normal diastolic function, 243 (49%) stage 1 DD; 131 (26%) stage 2 DD and 19 (4%) stage 3 DD. Patients with advanced DD had lower maximal METs achieved compared with those with normal diastolic function (OR 3.18(1.96 to 5.14) for stage 1 versus normal, and 3.21(1.89 to 5.43) for stage ?2 versus normal, p<0.0001 for both). After adjustment for demographics, comorbidities, echocardiographic parameters and haemodynamics, baseline DD was not an independent predictor of maximal METs achieved.

Conclusions

Although baseline DD is common in patients with HCM, it does not predict maximal METs achieved beyond traditional risk factors.

SUBMITTER: Aljaroudi WA

PROVIDER: S-EPMC3533067 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationship between baseline resting diastolic function and exercise capacity in patients with hypertrophic cardiomyopathy undergoing treadmill stress echocardiography: a cohort study.

Aljaroudi Wael A WA Desai Milind Y MY Alraies M Chadi MC Thamilarasan Maran M Menon Venu V Rodriguez L Leonardo LL Smedira Nicholas N Grimm Richard A RA Lever Harry M HM Jaber Wael A WA

BMJ open 20121212 6

<h4>Objective</h4>Diastolic dysfunction (DD) is often incriminated in the symptomatology of patients with hypertrophic cardiomyopathy (HCM), but with limited supporting data. This study sought to assess the relationship between baseline diastolic function and exercise capacity in patients with HCM.<h4>Design</h4>Retrospective study.<h4>Setting</h4>Tertiary referral centre from Cleveland, Ohio, USA.<h4>Participants</h4>695 consecutive patients with a diagnosis of HCM who underwent exercise stress ...[more]

PMID: 23242244

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Project description:AIMS:Several mutations in the ventricular myosin regulatory light chain (RLC) were identified to cause familial hypertrophic cardiomyopathy (FHC). Based on our previous cellular findings showing delayed calcium transients in electrically stimulated intact papillary muscle fibres from transgenic Tg-R58Q and Tg-N47K mice and, in addition, prolonged force transients in Tg-R58Q fibres, we hypothesized that the malignant FHC phenotype associated with the R58Q mutation is most likely related to diastolic dysfunction. METHODS AND RESULTS:Cardiac morphology and in vivo haemodynamics by echocardiography as well as cardiac function in isolated perfused working hearts were assessed in transgenic (Tg) mutant mice. The ATPase-pCa relationship was determined in myofibrils isolated from Tg mouse hearts. In addition, the effect of both mutations on RLC phosphorylation was examined in rapidly frozen ventricular samples from Tg mice. Significantly, decreased cardiac function was observed in isolated perfused working hearts from both Tg-R58Q and Tg-N47K mice. However, echocardiographic examination showed significant alterations in diastolic transmitral velocities and deceleration time only in Tg-R58Q myocardium. Likewise, changes in Ca(2+) sensitivity, cooperativity, and an elevated level of ATPase activity at low [Ca(2+)] were only observed in myofibrils from Tg-R58Q mice. In addition, the R58Q mutation and not the N47K led to reduced RLC phosphorylation in Tg ventricles. CONCLUSION:Our results suggest that the N47K and R58Q mutations may act through similar mechanisms, leading to compensatory hypertrophy of the functionally compromised myocardium, but the malignant R58Q phenotype is most likely associated with more severe alterations in cardiac performance manifested as impaired relaxation and global diastolic dysfunction. At the molecular level, we suggest that by reducing the phosphorylation of RLC, the R58Q mutation decreases the kinetics of myosin cross-bridges, leading to an increased myofilament calcium sensitivity and to overall changes in intracellular Ca(2+) homeostasis.

Project description:BackgroundPerfusion defects during stress can occur in hypertrophic cardiomyopathy (HCM) from either structural or functional abnormalities of the coronary microcirculation. In this study, vasodilator stress myocardial contrast echocardiography (MCE) was used to quantify and spatially characterize hyperemic myocardial blood flow (MBF) deficits in HCM.MethodsRegadenoson stress MCE was performed in patients with septal-variant HCM (n = 17) and healthy control subjects (n = 15). The presence and spatial distribution (transmural diffuse, patchy, subendocardial) of perfusion defects was determined by semiquantitative analysis. Kinetic analysis of time-intensity data was used to quantify MBF, microvascular flux rate (β), and microvascular blood volume. In patients undergoing septal myectomy (n = 3), MCE was repeated > 1 years after surgery. RESULTS: In HCM subjects, perfusion defects during stress occurred in the septum in 80%, and in non-hypertrophied regions in 40%. The majority of septal defects (83%) were patchy or subendocardial, while 67% of non-hypertrophied defects were transmural and diffuse. On quantitative analysis, hyperemic MBF was approximately 50% lower (p < 0.001) in the hypertrophied and non-hypertrophied regions of those with HCM compared to controls, largely based on an inability to augment β, although hypertrophic regions also had blood volume deficits. There was no correlation between hyperemic MBF and either percent fibrosis on magnetic resonance imaging or outflow gradient, yet those with higher degrees of fibrosis (≥ 5%) or severe gradients all had low septal MBF during regadenoson. Substantial improvement in hyperemic MBF was observed in two of the three subjects undergoing myectomy, both of whom had severe pre-surgical outflow gradients at rest.ConclusionPerfusion defects on vasodilator MCE are common in HCM, particularly in those with extensive fibrosis, but have a different spatial pattern for the hypertrophied and non-hypertrophied segments, likely reflecting different contributions of functional and structural abnormalities. Improvement in hyperemic perfusion is possible in those undergoing septal myectomy to relieve obstruction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02560467.

Dataset Information

Relationship between baseline resting diastolic function and exercise capacity in patients with hypertrophic cardiomyopathy undergoing treadmill stress echocardiography: a cohort study.

Objective

Design

Setting

Participants

Primary and secondary outcome measures

Results

Conclusions

Publications

Relationship between baseline resting diastolic function and exercise capacity in patients with hypertrophic cardiomyopathy undergoing treadmill stress echocardiography: a cohort study.

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