Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.

Hypertrophic cardiomyopathy and left ventricular non-compaction:Distinct diseases or variant phenotypes of a single condition?

Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM may present with an intraventricular or LV outflow tract obstruction,diastolic dysfunction,myocardial fibrosis and/or ventricular arrhythmias.Differentiating HCM from other diseases associated with LV hypertrophy,such as hypertension,aortic stenosis,or LV non-compaction(LVNC),can at times be challenging.LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae,often accompanied by increased LV myocardial mass.Previous studies indicate that the LVNC phenotype may be observed in up to 5%of the general population;however,in most cases,it is a benign finding with no impact on clinical outcomes.Nevertheless,LVNC can occasionally lead to LV systolic dysfunction,manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy,with an increased risk of thrombus formation and arterial embolism.In extreme cases,where LVNC is associated with a very thickened LV wall,it can even mimic HCM.There is growing evidence of an overlap between HCM and LVNC,including similar genetic mutations and clinical presentations.This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are,in fact,two distinct entities.

Predicting apical hypertrophic cardiomyopathy using T-wave inversion:Three case reports

BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(GNTs)in left-sided chest leads are the hallmark electrocardiogram(ECG)change of AHCM.CASE SUMMARY The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years.The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years.The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo.In all three cases,GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out.CONCLUSION Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities,confirming the early predictive value of ECG for AHCM.

Clivus-involved immunoglobulin G4 related hypertrophic pachymeningitis mimicking meningioma:A case report

BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.

Dynamic changes of autophagy during hypertrophic scar formation and the role of autophagy intervention

Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。

WJC 6~th Anniversary Special Issues(3):Cardiomyopathy Hypertrophic cardiomyopathy in 2013:Current speculations and future perspectives

Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.

Multimodality imaging in apical hypertrophic cardiomyopathy

Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the firstline imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease.

Speckle tracking echocardiography to assess regional ventricular function in patients with apical hypertrophic cardiomyopathy

AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.

Gene expression profile of hypertrophic chondrocytes treated with H2O2:A Preliminary investigation

Objective To identify the osteogenesis genes whose expression is altered in hypertrophic chondrocytes treated with H2 O2.Methods Murine chondrogenitor cells(ATDC5) were differentiated into hypertrophic chondrocytes by InsulinTransferrin-Selenium(ITS) treatment, and then treated with H2 O2. Suitable conditions(concentration, time) were determined by using the MTT assay. After total RNA isolation and cD NA synthesis, the levels of 84 genes were determined using the PCR array, whereas quantitative RT-PCR was carried out to validate the PCR array data. Results We identified 9 up-regulated genes and 12 down-regulated genes, encoding proteins with various functions, such as collagen proteins, transcription factors, proteins involved in skeletal development and bone mineral metabolism, as well as cell adhesion molecules. Quantitative RT-PCR confirmed the altered expression of 5 down-regulated genes(Smad2, Smad4, transforming growth factor β receptor 1, transforming growth factor β receptor 3, and matrix metalloproteinase 10). Conclusions H2 O2 significantly changed the expression of several genes involved in a variety of biological functions. Because of the link between oxidative damage and Kashin-Beck disease, these genes may also be involved in the deep-zone necrosis of the cartilage observed in Kashin-Beck disease.

Complete pancreatic heterotopia of gallbladder with hypertrophic duct simulating an adenomyoma

The gallbladder is an unusual location of pancreatic heterotopia, defined as the presence of pancreatic tissue lacking anatomical and vascular continuity with the main body of the gland. A 28-year-old man presented with anorexia, nausea and pain in the right upper abdomen. On physical examination, the abdomen was tender to palpation and Murphy sign was positive. The patient underwent a cholecystecomy. This case, in our opinion, is very interesting since it permits to consider a controversial issue in the pathology of the gallbladder. The histological appearance of ductal structure in pancreatic heterotopia resembles the histological picture of both Aschoff-Rokitansky （AR） sinuses and adenomyomas. This finding suggests that these lesions are linked by a common histogenetic origin. We suggest that the finding of an adenomyoma in the gallbladder should prompt an extensive sampling of the organ in order to verify the coexistence of pancreatic rests.

Video capsule endoscopy and CT enterography in diagnosing adult hypertrophic pyloric stenosis

Primary adult hypertrophic pyloric stenosis is a rare but important cause of gastric outlet obstruction that may be misdiagnosed as idiopathic gastroparesis.Clinically,patients present with early satiety,abdominal fullness,nausea,epigastric discomfort and eructation.Permanent gastric retention of a video capsule endoscope is diagnostic in differentiating between the two diseases,in the absence of an organic gastric outlet obstruction.This case presents the longest video capsule retention in the medical literature to date.It is also the first case report of adult hypertrophic pyloric stenosis diagnosed with video capsule endoscopy or a computed tomography scan.Finally,an unusual"plugging"of the gastric outlet with free floating capsule has an augmented effect on disease physiology and on patient’s symptoms.

Apical hypertrophic cardiomyopathy

We describe a patient with asymptomatic apical hypertrophic cardiomyopathy(AHCM)who later developed cardiac arrhythmias,and briefly discuss the diagnostic modalities,differential diagnosis and treatment option for this condition.AHCM is a rare form of hypertrophic cardiomyopathy which classically involves the apex of the left ventricle.AHCM can be an incidental finding,or patients may present with chest pain,palpitations,dyspnea,syncope,atrial fibrillation,myocardial infarction,embolic events,ventricular fibrillation and congestive heart failure.AHCM is frequently sporadic,but autosomal dominant inheritance has been reported in few families.The most frequent and classic electrocardiogram findings are giant negative T-waves in the precordial leads which are found in the majority of the patients followed by left ventricular(LV)hypertrophy.A transthoracic echocardiogram is the initial diagnostic tool in the evaluation of ACHM and shows hypertrophy of the LV apex.AHCM may mimic other conditions such as LV apical cardiac tumors,LV apical thrombus,isolated ventricular non-compaction,endomyocardial fibrosis and coronary artery disease.Other modalities,including left ventriculography,multislice spiral computed tomography,and cardiac magnetic resonance imagings are also valuable tools and are frequently used to differentiate AHCH from other conditions.Medications used to treat symptomatic patients with AHCM include verapamil,beta-blockers and antiarrhythmic agents such as amiodarone and procainamide.An implantable cardioverter defibrillator is recommended for high risk patients.

Hypertrophic cardiomyopathy: Can the noninvasive diagnostic testing identify high risk patients?

Hypertrophic cardiomyopathy(HCM) is the most common cause of sudden cardiac death(SCD) in the young, particularly among athletes. Identifying high risk individuals is very important for SCD prevention. The purpose of this review is to stress that noninvasive diagnostic testing is important for risk assessment. Extreme left ventricular hypertrophy and documented ventricular tachycardia and fibrillation increase the risk of SCD. Fragmented QRS and T wave inversion in multiple leads are more common in high risk patients. Cardiac magnetic resonance imaging provides complete visualization of the left ventricular chamber, allowing precise localization of the distribution of hypertrophy and measurement of wall thickness and cardiac mass. Moreover, with late gadolinium enhancement, patchy myocardial fibrosis within the area of hypertrophy can be detected, which is also helpful in risk stratification. Genetic testing is encouraged in all cases, especially in those with a family history of HCM and SCD.

RISK OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY UNDERGOING NONCARDIAC SURGERY

Objective To determine the risk of noncardiac surgery in patients with hypertrophic cardiomyopathy.Methods We reviewed the medical records of all patients who were diagnosed as hypertrophic cardiomyopathy at Peking Union Medical College Hospital from January 1998 to August 2006 and identified 24 patients who subsequently underwent noncardiac surgery.Results There were no intraoperative cardiac events.Postoperative cardiac events were identified in 3 patients including 1 death due to acute myocardial infarction and 2 episodes of transient hypotension.Conclusions The risk of anesthesia and noncardiac surgery is low in patients with hypertrophic cardiomyopathy.During the perioperative period,beta-blockers and/or calcium channel blockers should be given;vasodilator and inotropic agents should be avoided due to the side effects on hemodynamics.

Pulmonary vein isolation implemented by second-generation cryoballoon for treating hypertrophic cardiomyopathy patients with symptomatic atrial fibrillation:a case-control study

Background Atrial fibrillation(AF)is a generally acknowledged turning-point of the natural history of hypertrophic cardiomyopathy(HCM);however,data from the cryoballoon ablation(CBA)for AF in HCM patients are relatively scarce.The study aimed to evaluate the efficacy and safety of CBA in HCM patients with AF.Methods We retrospectively analyzed HCM patients among 1253 patients with symptomatic AF who underwent CBA for pulmonary vein isolation in a single center.The study analyzed the AF recurrence and assessed the CBA indexes,including nadir temperature,time-to-isolation,CBA failure,pulmonary vein potentials(PVPs),and redo procedure.Results A total of 108 patients were included(mean age:59.0±6.9 years),27 patients(25%)had HCM,with the median follow-up duration of 25.5 months.The one-year AF-free rates were 79.0%vs.63.0%(non-HCM vs.HCM),while the two-year AF-free rates were 77.8%vs.55.1%[hazard ratio(HR)=2.758,log-rank P=0.024].Patients with persistent AF had poor AF-free rates compared to those with paroxysmal AF(P<0.001).The CBA failure was the most common in the right inferior pulmonary veins,which had the lowest PVPs.Multivariate Cox regression analysis indicated that HCM and persistent AF were risk factors for AF recurrence(HR=2.74,95%CI:1.29–5.79,P=0.008;and HR=3.97,95%CI:1.85–8.54,P<0.001,respectively).Conclusions The CBA can be effectively and safely used to treat HCM patients with symptomatic AF.The freedom from AF for HCM patients after CBA is relatively low compared to that for non-HCM patients.

Left Ventricular Regional Systolic Function in Patient with Hypertrophic Cardiomyopathy by Quantitative Tissue Velocity Imaging

The left ventricular regional systolic functions in patients with hypertrophic cardiomyopathy （HCM） were assessed by using quantitative tissue velocity imaging （QTVI）. Left ventricular （LV） regional myocardial velocity along long- and short-axis in 31 HCM patients and 20 healthy subjects were analyzed by QTVI, and the regional myocardial systolic peak velocities （MVS） were measured. Mean MVS at each level including mitral annular, basal, middle and apical segments were calculated. The ratio of MVS along long-axis to that along short-axis （Ri） at basal and middle segments of the LV posterior wall and ventricular septum were calculated. The results showed that mean MVS was slower at each level including mitral annular, basal, middle and apical segments in the HCM patients than that in the healthy subjects （P〈0.01）. There were no significant differences in mean MVS between obstructive and non-obstructive groups in HCM patients. MVS of all regional myocardial segments along long-axis in the HCM patients were significantly slower than that in the healthy subjects （P〈0.05）, but there was no significant difference in MVS of all regional myocardial segments along long-axis between hypertrophied and non-hypertrophied group in the HCM patients. Ri was significantly lower in the HCM patients than that in the healthy subjects. The LV regional myocardial contractility along long-axis was impaired not only in the hypertrophied wall but also in the non-hypertrophied one in patients with HCM, suggesting that QTVI can assess accurately LV regional systolic function in patient with HCM and provides a novel means for an early diagnosis before and independent of hypertrophy.

Assessment of Regional Myocardial Function in Patients with Hypertrophic Cardiomyopathy by Tissue Strain Imaging

The value of tissue strain imaging （SI） in regional myocardial systolic and diastolic func tion assessment was studied. In 18 patients with nonobstructive hypertrophic cardiomyopathy （HCM） and 20 age-matched healthy subjects, regional myocardial longitudinal peak systolic strain in eject time （represented by εet） was measured at basal, mid and apical segments of septal, lateral and posterior walls of the left ventricle （LV） and compared between groups, εet had no significant difference between segments in control group （P〉0.05）, which displayed a decreasing trend from basal segments to apical ones. εet in the HCM group was significantly decreased （P（0. 05） as compared with that in the healthy group. In the HCM group, εet in the midseptum was significantly less than at the basal and apical septum, and was also less than at the rest LV walls in the same group （P〉0.01）. The systolic reversed εet was noticed in 35% of the hypertrophic segments in HCM group. Significantly negative correlation existed between the absolute value of εet and wall thickness in the midseptum （r= -0.83）. The post-systolic strain（PSS） segment number the and amplitudes in healthy group were significantly less than those in HCM group （P〈0.05）. Both regional myocardial systolic and diastolic functions were impaired in hypertrophic or non-hypertrophic segments in patients with the HCM, especially in hypertrophic segments. Strain imaging technique is a sensitive and accura tool in myocardial dysfunction assessment.

Bilateral Hypertrophic Olivary Degeneration after Pontine Hemorrhage: A Case Report

BACKGROUND Hemorrhage lesions may lead to bilateral hypertrophic olivary degeneration(HOD)through interruption of the dentato-rubral-olivary pathway.The pathological features of HOD are unusual neuronal trans-synaptic degenerative changes.CASE SUMMARY A 56-year-old female was admitted to our hospital because her lower extremities and left upper ones were unable to move for 3 mo,and the swelling of her right lower extremities became worse 3 days ago.She had a hypertension history.Her characteristic clinical manifestations are palatal myoclonus and nystagmus.The patient’s magnetic resonance imaging(MRI)results showed that she had bilateral HOD after an acute pontine hemorrhage.She was given symptomatic and supportive treatment.The gabapentin,the memantine and the trihexyphenidyl were taken twice a day each.The rehabilitation and psychotherapy were implemented.After 3 months of treatment,her eye symptoms improved.CONCLUSION Bilateral HOD is a rare phenomenon after pontine hemorrhage.The key to diagnosis lies in the clinical manifestations and MRI results.

Effect of ALA-PDT on the expressions of MMP-9, MMP-13 and TIMP-1 of hypertrophic scar model in rabbit ears

Objective: To investigate the effect of 5-aminolevulinic(ALA)-photodynamic therapy(PDT) on the expressions of MMP-9, MMP-13 and TIMP-1 of hypertrophic scar model in rabbit ears, and analyze the possible therapeutic mechanisms of ALA-PDT treatment to hypertrophic scars of rabbit ears. Methods: The experimental animals were randomly divided into normal control, negative control, high concentration of ALA-PDT, low concentration of ALA-PDT and PDT groups. The latter three groups received ALA-PDT treatment or PDT treatment once a week for 3 weeks. The specimens of the rabbits were collected respectively 1, 2 and 3 months after treatment to be used for RT-PCR and Western-blot test. Results: 1, 2 and 3 months after PDT treatment, the expressions of MMP-9 and MMP-13(including mRNA and protein) in hypertrophic scar tissues of three treatment groups were significantly higher than those of the negative control group(P<0.01), and the expression of TIMP-1 mRNA and protein of three treatment groups were significantly lower than that of the negative control group(P<0.01). There were also significant differences between high-concentration ALA-PDT treatment group and the low one(P<0.05). Conclusion: ALA-PDT is effective in treating hypertrophic scars of rabbit ears, and its possible therapeutic mechanisms are that ALA-PDT treatment generates oxidation activation effect to activate the activity of MMPs and induces the photoaging of fibroblasts of hypertrophic scar tissues of rabbit ears to inhibit the activity of TIMPs, which causes the up-regulation of MMPs and the down-regulation of TIMPs. Because of this, the degradation of collagen and ECM is accelerated and the formation of scars is suppressed.

ASSESSMENT OF DIASTOLIC FUNCTION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY BY DOPPLER TISSUE IMAGING

To determine the clinical application of pulsed Doppler tissue imaging in assessing the left ventricular diasto-lic function and in discriminating between normal subjects and patients with hypertrophic cardiomyopathy with various stages of diastolic dysfunction. Methods We measured the peak diastolic velocities of mitral annulus in 81 patients with hypertrophic cardiomyopathy with various stages of diastolic dysfunction and 50 normal volunteers by Doppler tissue imaging using the apical window at 2-ch-amber and long apical views, respectively. The myocardial velocities were determined with use of variance F statistical analysis. Results Early diastolic myocardial velocities of mitral annulus were higher in normal subjects than in patients with hy-pertrophic cardiomyopathy with either delayed relaxation, pseudonormal filling, or restrictive filling. However, peak myocar-dial velocities of mitral annulus during atrial contraction were similar in normal subjects and patients with hypertrophic cardiomyopathy. Conclusion Doppler tissue imaging can directly reflect upon left diastolic ventricular function. Early phase of diastole was the best discriminator between control subjects and patients with hypertrophic cardiomyopathy.