Distribution Of Left Ventricular Hypertrophy Research Articles

Associations between electrocardiographic findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy

BackgroundThe relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood. MethodsOne hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis. ResultsIn ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV. ConclusionsIn patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment.

DISTRIBUTION OF THE DEGREE OF RIGHT VENTRICULAR HYPERTROPHY WITH DIFFERENT SEVERITY OF LEFT VENTRICULAR HYPERTROPHY IN ARTERIAL HYPERTENSION

Objective: To study the interrelation of the influence of left ventricular hypertrophy (LVH) on the frequency of the distribution of the degree of right ventricular hypertrophy (RVH) in patients who died suddenly during their lifetimes who suffered from arterial hypertension according to an autopsy Design and method: A retrospective study was conducted, which explored the autopsy protocols of patients suffered from hypertension (1999-2014) in Semey, Kazakhstan, suffered from hypertension during life and died suddenly. The normal wall thickness of the left ventricle was taken as 0.7-1.2 cm, the right ventricle 0.2-0.3 cm. The hypertrophy of the walls of the left and right ventricles was conventionally divided into 2 degrees. The hypertrophy of the walls of the left ventricle and the right ventricle was conditionally divided into 2 degrees, LVH: I degree - 1.3-2.0 cm, II degree - 2.1 or more; RVH: I degree - 0.4-0.6 cm, II degree - 0.7 cm or more. Results: When conducting a study of these protocols of persons, the thickness of the right ventricle was presented in 614 autopsy protocols. The distribution of LVH was the following: 1 degree 51.1%; 2 degree 48.9%. While the data on the distribution of RVH are as follows: the norm is 13%; 1st degree 33.9%; 2 degree 53.1%. At the same time, with 1 degree of left ventricular hypertrophy, the following distribution of RVH is noted: the norm is 22.6%; 1st degree - 46.8%; 2 degree - 30.6%. Then with 2 degrees of LVH, respectively: 3%, 20.3%, 76.7%, p <0.0001. At 1 and 2 degrees of LVH, the frequency of detection of 2-degree RVH was, respectively, 30.6% and 76.8%. A direct correlation was found between the wall thickness of the left and right ventricles (r = 0.478). Conclusions: RVH is a common symptom in hypertension, up to 87% according to autopsy examination. LVH 1 and 2 degrees in the study group were equally distributed. The more pronounced the values of the degree of LVH, the more pronounced the degree of RVH. With LVH of the 2 degree, 2 times more often detected 2nd degree RVH.

Clinical features and natural history of RASopathy-associated hypertrophic cardiomyopathy in children

Abstract Background The RASopathies are a group of genetic disorders caused by germline mutations in genes encoding components of the RAS/MAPK signalling pathway and frequently associated with hypertrophic cardiomyopathy (HCM). The clinical features and outcomes of RASopathy-related HCM are incompletely understood and most published studies are limited by relatively small numbers and incomplete clinical characterisation. Purpose To describe the clinical features outcomes in a large, single-centre cohort of patients with RASopathy-associated HCM diagnosed <18 years. Methods Data from 105 patients [68 (64.8%) males] diagnosed in childhood with RASopathy-associated HCM at a single specialist centre between 1985 and 2020 were retrospectively analysed. Results The RASopathy diagnosis was Noonan syndrome in 69 patients (65.7%); NSML in 10 (9.5%); CFC in 6 (5.7%); Costello in 5 (4.8%) and 15 patients (14.2%) had another Noonan-like variant. 72 patients (68.6%) had a pathogenic/likely pathogenic variant in a RAS-MAPK gene, most commonly PTPN11 [n=25 (34.7%)], followed by RAF 1 [n=13 (18.1%)]. 100 patients (95.2%) were probands, 9 (8.6%) had family history of cardiomyopathy and 2 (1.9%) family history of sudden cardiac death (SCD). 52 (49.5%) had concomitant congenital heart defects (CHD) [ASD 13 (25%), VSD 6 (11.5%), PDA 1 (1.9%), >1 CHD 32 (61.5%)]. 29 (27.6%) had symptoms at baseline assessment and 56 (53.3%) were on cardiac medication. The distribution of left ventricular hypertrophy (LVH) was concentric in 47 (44.7%); 32 (30.5%) had asymmetric septal hypertrophy (ASH), and undocumented in 25 patients (23.8%). 45 patients (42.9%) had biventricular hypertrophy (BVH). Resting left ventricular outflow tract obstruction (LVOTO) was present in 39 (37.1%) with haemodynamically significant LVOTO (≥50mmHg) in 23 (21.9%). Resting right ventricular outflow tract obstruction (RVOTO) was present in 21 (20%). Over a median follow up time of 6 years, 19 patients (18.1%) died [1 (5.3%) SCD; 2 (10.5%) due to Heart Failure-related death; 1 (5.3%) due to another CVS cause; 5 (26.3%) due to a non-CVS cause and for 10 (52.6%) cause of death was unknown]. Incidence rate of death was calculated at 2.7 deaths per 100 person-years. Surgical septal myectomy was performed in 9 patients (8.6%) and 3 (2.9%) underwent cardiac transplantation. 14 patients (13.3%) suffered arrhythmic events [atrial tachycardia 6 (42.9%), Non-Sustained Ventricular Tachycardia 4 (3.8%), and Ventricular Tachycardia/Ventricular Fibrillation 4 (3.8%)]. Conclusion To our knowledge, this is the largest cohort of RASopathy-associated HCM. The findings show a heterogeneous clinical presentation with a high prevalence of morbidity and mortality. Further work is needed to determine predictors of outcome in this population. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Onassis Foundation

Identification of Fabry Disease in a Tertiary Referral Cohort of Patients with Hypertrophic Cardiomyopathy

BackgroundFabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease–specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy. MethodsWe studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene. ResultsIn 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy. ConclusionsThese observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease–affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy.

Association of Late Gadolinium Enhancement and Degree of Left Ventricular Hypertrophy Assessed on Cardiac Magnetic Resonance Imaging With Ventricular Tachycardia in Children With Hypertrophic Cardiomyopathy

There are limited data on the clinical significance of left ventricular (LV) mass and late gadolinium enhancement (LGE) in pediatric hypertrophic cardiomyopathy (HC). We reviewed cardiovascular magnetic resonance (CMR) studies of children with HC to investigate the associations between the extent and distribution of LGE and LV mass with ventricular tachycardia (VT) in children with HC. A blinded observer reviewed CMR studies for the presence and distribution of LV hypertrophy and LGE using a 17-segment model. The primary outcome was VT. LGE was present 17 of 33 subjects (52%). VT was present on outpatient Holter monitor or exercise stress test in 7 patients, of which 5 patients (71%) had LGE. Each additional segment of LGE was associated with an increase in the odds of VT (odds ratio [OR] 1.4, 95% CI 1.1 to 1.9) and fewer than 5 segments with LGE had 93% specificity for the presence or absence of VT (OR 0.06, 95% CI 0.01 to 0.5). VT was more common in patients with LGE in the apical septal (p= 0.03), basal inferoseptal (p<0.01), and basal inferior (p= 0.04) segments, whereas LGE in more commonly involved segments (midanteroseptal and midinferoseptal) was not associated with VT (p= 0.13, 0.26). Patients with VT had greater LV mass index (76.4 ± 40.4g/m(2.7) vs 50.9 ± 24.3g/m(2.7); p= 0.03). Each centimeter of increased maximum LV thickness was associated with increased likelihood of VT (OR 2.9, 95% CI 1.2 to 6.8). In conclusion, in pediatric HC, CMR to evaluate the extent and pattern of LGE, LV mass index, and maximum LV thickness may help to identify children with HC at risk of VT.

Degree and distribution of left ventricular hypertrophy as a determining factor for elevated natriuretic peptide levels in patients with hypertrophic cardiomyopathy: insights from cardiac magnetic resonance imaging

Whether the left ventricular (LV) mass index (LVMI) and LV volumetric parameters are associated independently with natriuretic peptide levels is unclear in hypertrophic cardiomyopathy (HCM). Therefore, we investigated which parameters have an independent relationship with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in HCM patients using echocardiography and cardiac magnetic resonance imaging (CMR). A total of 103 patients with HCM (82 men, age 53 ± 12 years) were evaluated. Echocardiographic evaluations included left atrial volume index (LAVI) and early diastolic mitral inflow E velocity to early annular Ea velocity ratio (E/Ea). LVMI, maximal wall thickness and LV volumetric parameters were measured using CMR. The median value of NT-proBNP level was 387.0 pg/ml. The mean NT-proBNP level in patients with non-apical HCM (n = 69; 36 patients with asymmetric septal hypertrophy, 11 with diffuse, and 22 with mixed type) was significantly higher than in those with apical HCM (n = 34, P < 0.001). NT-proBNP level was negatively correlated with LV end-diastolic volume (LVEDV) (r = -0.263, P = 0.007) and positively with LVMI (r = 0.225, P = 0.022) and maximal wall thickness (r = 0.495, P < 0.001). Among the echocardiographic variables, LAVI (r = 0.492, P < 0.001) and E/Ea (r = 0.432, P < 0.001) were correlated with NT-proBNP. On multivariable analysis, non-apical HCM, increased maximal wall thickness and LAVI were independently related with NT-proBNP. Severity of LV hypertrophy and diastolic parameters might be important in the elevation of NT-proBNP level in HCM. Therefore, further evaluation of these parameters in HCM might be warranted.

Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure

Hypertrophic cardiomyopathy (HCM), an inherited primary cardiac disorder mostly caused by defective sarcomeric proteins, serves as a model to investigate left ventricular hypertrophy (LVH). HCM manifests extreme variability in the degree and distribution of LVH, even in patients with the same causal mutation. Genes coding for renin-angiotensin-aldosterone system components have been studied as hypertrophy modifiers in HCM, with emphasis on the angiotensin (Ang) II type 1 receptor (AT(1)R). However, Ang II binding to Ang II type 2 receptors (AT(2)R) also has hypertrophy-modulating effects. We investigated the effect of the functional +1675 G/A polymorphism (rs1403543) and additional single nucleotide polymorphisms in the 3' untranslated region of the AT(2)R gene (AGTR2) on a heritable composite hypertrophy score in an HCM family cohort in which HCM founder mutations segregate. We find significant association between rs1403543 and hypertrophy, with each A allele decreasing the average wall thickness by ~0.5 mm, independent of the effects of the primary HCM causal mutation, blood pressure and other hypertrophy covariates (p = 0.020). This study therefore confirms a hypertrophy-modulating effect for AT(2)R also in HCM and implies that +1675 G/A could potentially be used in a panel of markers that profile a genetic predisposition to LVH in HCM.

In Vivo Measurement of Mitral Leaflet Surface Area and Subvalvular Geometry in Patients With Asymmetrical Septal Hypertrophy

Background— Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy. Methods and Results— Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness &gt;16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II ( P &lt;0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; P =0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; P =0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient ( R 2 =0.83, P &lt;0.001); its independent determinants were left ventricular end-systolic volume ( P =0.0183), indexed total ML area ( P =0.0108), inter-PM distance ( P =0.0378), annular height ( P =0.0047), and LVOT hypertrophy index ( P =0.0098). Conclusions— Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM–mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention.

Clinical Summaries

Clinical Summaries

Relation of 12-Lead Electrocardiogram Patterns to Implanted Defibrillator-Terminated Ventricular Tachyarrhythmias in Hypertrophic Cardiomyopathy

Electrocardiographic (ECG) abnormalities are common in hypertrophic cardiomyopathy (HC) and have been associated with the distribution of left ventricular hypertrophy and myocardial fibrosis. Such abnormalities may predispose patients to electrophysiologic instability, ventricular arrhythmias, and sudden cardiac death (SCD). We studied 330 patients with HC who were judged clinically to be at high risk for SCD and therefore received automatic implantable cardioverter-defibrillators (ICDs). Surface 12-lead electrocardiograms acquired at the time of ICD implantation were analyzed and the ECG characteristics of patients with appropriate device interventions for ventricular tachycardia and fibrillation were compared to those patients without appropriate device interventions. The 330 patients were followed for 3.7 +/- 3.0 years after implantation and 57 patients (17%) had appropriate discharges. No differences in the ECG characteristics of patients with and without appropriate device interventions were identified. Markedly increased ECG voltages, QRS duration, left or rightward QRS axis, abnormal Q waves, and QTc or QT dispersion were not associated with appropriate ICD discharge. Conversely, normal electrocardiograms and electrocardiograms normal except for a repolarization abnormality in only 1 anatomic distribution were not associated with freedom from ICD discharge. Moreover, no combination of ECG variables was associated with the likelihood of an appropriate ICD discharge. In conclusion, in a cohort of patients with HC selected because of their high risk for SCD, 12-lead surface electrocardiogram did not predict subsequent appropriate ICD intervention for ventricular tachyarrhythmias and was not useful in risk stratification for sudden death.

Revelation of an obstructive hypertrophic cardiomyopathy in an elderly patient

Hypertrophic cardiomyopathy (HCM) is classified as a primary cardiomyopathy. HCM is a clinically heterogeneous but relatively common autosomal dominant genetic heart disease that probably is the most frequently occurring cardiomyopathy. HCM is characterized morphologically and defined by a hypertrophied, nondilated left ventriculum (LV) in the absence of another systemic or cardiac disease that is capable of producing the magnitude of wall thickening evident (e.g., systemic hypertension, aortic valve stenosis). Most HCM patients have the propensity to develop dynamic obstruction to LV outflow under resting or physiologically provocable conditions, produced by systolic anterior motion of the mitral valve with ventricular septal contact. The phenotypic features of HCM may develop at any age from infancy to adulthood, and are characterized by a great heterogeneity in the extent, magnitude, and distribution of left ventricular hypertrophy. Hypertrophic obstructive cardiomyopathy (HOCM) often leads to heart failure, severe ischemia, severe symptoms and death. Determination of the exact site of the hypertrophy and of the obstruction of the left ventricular outflow tract, in asymmetric septal hypertrophy, establishes which is the best treatment strategy. In the treatment of HOCM, drug therapy with negatively inotropic drugs, percutaneous transluminal septal myocardial ablation by alcohol-induced septal branch occlusion, surgical myectomy and DDD pacemaker therapy are considered the therapeutical options. We present a case of an obstructive hypertrophic cardiomyopathy in an 84-year-old Italian woman with a left ventricular outflow tract (LVOT) peak gradient with the Valsalva maneuver of 188 mm Hg and with a history of first episode of syncope.

Clinical Expression in Patients With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutation

To the Editor: Hypertrophic cardiomyopathy is a primary cardiac disorder, mostly genetically transmitted, with a heterogeneous clinical and morphological expression. Analysis of the clinical expression of several genetic alterations has previously focused mainly on unfavorable manifestations. In this regard, recent articles by Charron and colleagues1 and by Niimura and colleagues2 that describe delayed expression of cardiac hypertrophy and a favorable clinical course in patients with mutations in the gene for cardiac myosin-binding protein C (MyBP-C) are indeed important contributions to an understanding of phenotype-genotype correlations at the mild end of the spectrum of the disease. However, these reports did not include precise morphological distribution of left ventricular hypertrophy, which is of clinical importance in the diagnosis and management of patients with this disorder. We had opportunities to study 6 probands from 6 small Japanese families living in Kochi prefecture who were found to have the same mutation in the cardiac MyBP-C gene: …

Clinical Features of Hypertrophic Cardiomyopathy Caused by Mutation of a “Hot Spot” in the Alpha-Tropomyosin Gene

Objectives. We studied the clinical and genetic features of familial hypertrophic cardiomyopathy (FHC) caused by an Asp175Asn mutation in the alpha-tropomyosin gene in affected subjects from three unrelated families.Background. Correlation of genotype and phenotype has provided important information in FHC caused by beta-cardiac myosin and cardiac troponin T mutations. Comparable analyses of hypertrophic cardiomyopathy caused by alpha-tropomyosin mutations have been hampered by the rarity of these genetic defects.Methods. The haplotypes of three kindreds with FHC due to an alpha-tropomyosin gene mutation, Asp175Asn, were analyzed. The cardiac histopathologic findings of this mutation are reported. Distribution of left ventricular hypertrophy in affected members was assessed by two-dimensional echocardiography, and patient survival rates were compared.Results. Genetic studies defined unique haplotypes in the three families, demonstrating that independent mutations caused the disease in each. The Asp175Asn mutation caused cardiac histopathologic findings of myocyte hypertrophy, disarray and replacement fibrosis. The severity and distribution of left ventricular hypertrophy varied considerably in affected members from the three families (mean maximal wall thickness ± SD: 24 ± 4.5 mm in anterior septum of Family DT; 15 ± 2.7 mm in anterior septum and free wall of Family DB; 18 ± 2.1 mm in posterior septum of Family MI), but survival was comparable and favorable.Conclusions. Nucleotide residue 579 in the alpha-tropomyosin gene may have increased susceptibility to mutation. On cardiac histopathologic study, defects in this sarcomere thin filament component are indistinguishable from other genetic etiologies of hypertrophic cardiomyopathy. The Asp175Asn mutation can elicit different morphologic responses, suggesting that the hypertrophic phenotype is modulated not by genetic etiologic factors alone. In contrast, prognosis reflected genotype; near normal life expectancy is found in hypertrophic cardiomyopathy caused by the alpha-tropomyosin mutation Asp175Asn.(J Am Coll Cardiol 1997;29:635–40)

Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: Morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients

This study sought to achieve an understanding of the true structural heterogeneity of hypertrophic cardiomyopathy. The diversity and clinical significance of the morphologic expression of hypertrophic cardiomyopathy have not been fully defined within this broad disease spectrum. Patterns of left ventricular hypertrophy were characterized by two-dimensional echocardiography in a large study cohort of 600 patients (7 to 79 years old, mean age 45; 393 [66%] men) consecutively studied at two referral centers. Left ventricular wall thickness was 15 to 52 mm (mean [+/- SD] 22.3 +/- 5). A multitude of patterns of asymmetric left ventricular hypertrophy were identified, with the most common showing diffuse involvement of substantial portions of both ventricular septum and free wall. Of 16 possible patterns of left ventricular hypertrophy, 12 (78%) were identified among the 600 patients. Hypertrophy most commonly involved two left ventricular segments (228 patients [38%]) or three or more segments (202 patients [34%]), but was also localized to one segment in a substantial number of patients (170 [28%]). The anterior portion of the ventricular septum was the region of the left ventricle that most frequently showed thickening (573 patients [96%]), and was also the predominant site of hypertrophy in most patients (492 patients [83%]). Patterns of wall thickening that were either concentric (i.e., symmetric) or confined to the apex were particularly uncommon (in 1% each). 1) In hypertrophic cardiomyopathy, the distribution of left ventricular hypertrophy is characteristically asymmetric and particularly heterogeneous, encompassing most possible patterns of wall thickening, from extensive and diffuse to mild and segmental, and with no single morphologic expression considered typical or classic. 2) A greater extent of left ventricular hypertrophy was associated with younger age and more marked mitral valve systolic anterior motion and outflow obstruction but showed no relation to either magnitude of symptoms or gender.

Long-term Clinical and Echocardiographic Follow-up After Surgical Correction of Hypertrophic Obstructive Cardiomyopathy With Extended Myectomy and Reconstruction of the Subvalvular Mitral Apparatus

The standard surgical approach to hypertrophic obstructive cardiomyopathy (HOCM) was modified in the present series with a combination of extended myectomy with partial excision and mobilization of the papillary muscles. Between 1979 and 1992, 58 patients (38 men and 20 women; mean age, 49 +/- 24 years) with HOCM were operated on with the use of this different technique. Their intraventricular gradients were 79 +/- 33 (+/- SD) mm Hg at rest and increased to 147 +/- 48 mm Hg with provocative maneuvers. Mild-to-moderate mitral regurgitation was present in 60% of the patients, and severe regurgitation was present in 5%. Ten patients required additional aortocoronary bypass graft surgery. Follow-up (mean, 84 months) was complete (100%). Hemodynamic improvement was documented by a significant (P < .01) decrease in left ventricular end-diastolic pressure from 19 +/- 9 to 14 +/- 6 mm Hg and reduction of basal outflow tract gradients to 5 +/- 7 mm Hg at rest and 16 +/- 24 mm Hg after provocation. Late mortality was 1.4% per patient-year, and no sudden cardiac deaths occurred during follow-up. Functional status was excellent for 84% of the patients; 8 patients were in New York Heart Association functional class III, and none were in class IV. Echocardiography revealed no outflow tract obstruction. Extended myectomy and reconstruction of the subvalvular mitral apparatus in HOCM result in excellent functional improvement with relief of outflow tract obstruction. The technique can be performed safely despite its more aggressive surgical nature and allows an individualized strategy depending on the patient's extent and distribution of left ventricular hypertrophy.

Variability between current definitions of 'normal' ambulatory blood pressure. Implications in the assessment of white coat hypertension.

The assessment of white coat hypertension is complicated by the lack of generally agreed-on normal limits of ambulatory blood pressure. To assess the influence of four of these limits on the prevalence of white coat hypertension and the corresponding distribution of left ventricular hypertrophy, we performed 24-hour ambulatory blood pressure monitoring and echocardiographic studies in 346 untreated patients with essential hypertension and 47 age-matched normotensive control subjects. The upper limits of normal daytime ambulatory blood pressure were lower using standards drawn from clinically normotensive populations than using standards drawn, partly or entirely, from general populations. The prevalence of white coat hypertension differed markedly using the different standards, being 12.1%, 16.5%, 28.9%, and 53.2% (chi 2 = 346.0, p less than 0.0001). Left ventricular mass index averaged 77 g/m2 in the control group, 85 g/m2 in the two groups with white coat hypertension defined by using standards drawn from normotensive populations (both comparisons not significant versus control group), and 90 and 98 g/m2 in the two groups with white coat hypertension defined by using the other two standards (both p less than 0.01 versus control group). The prevalence of echocardiographic left ventricular hypertrophy was 0% in the control group, 2.4% and 3.5% in the two groups with white coat hypertension defined by using standards drawn from normotensive populations, and 9.0% and 14.7% in the other two groups with white coat hypertension (p less than 0.05 and p less than 0.01, respectively, versus control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of surgical relief of outflow obstruction on thallium perfusion abnormalities in hypertrophic cardiomyopathy.

To assess the impact of surgical relief of left ventricular outflow obstruction on myocardial perfusion abnormalities in patients with obstructive hypertrophic cardiomyopathy, 20 symptomatic patients who underwent a septal myectomy or mitral valve replacement were studied with assessment of myocardial perfusion during exercise by 201Tl emission computed tomography before and 6 months after surgery. Before surgery, 15 patients had myocardial perfusion defects during exercise that completely normalized at rest, one patient had both reversible and fixed perfusion defects, two patients had fixed defects only, and two patients had normal exercise and rest thallium scans. After surgical relief of left ventricular outflow obstruction (basal gradient reduced from 62 +/- 40 to 7 +/- 12 mm Hg, p less than 0.001; peak provokable gradient reduced from 131 +/- 27 to 49 +/- 36 mm Hg, p less than 0.001), repeat exercise thallium studies showed complete normalization of perfusion defects in 11 patients, including the two patients with fixed defects alone before surgery, and improvement in the magnitude and distribution of perfusion defects in five additional patients. This was associated with a significant reduction in the number of patients with reversible regional defects (five patients compared with 13 patients before surgery, p = 0.026) and of patients with endocardial hypoperfusion (four patients compared with 12 patients before surgery, p = 0.024). Furthermore, increased lung uptake of thallium was noted in five patients after surgery, compared with 12 patients before surgery (p = 0.055). Only two patients with reversible perfusion defects before surgery had unchanged postoperative studies. However, four patients acquired new fixed defects as a consequence of surgery, and two of these four had the greatest severity and distribution of left ventricular hypertrophy by echocardiography. These four patients experienced a substantially greater decrease in ejection fraction (-26 +/- 15%) after surgery than the remaining patients (-3 +/- 14%, p less than 0.01). Surgical relief of left ventricular outflow obstruction results in normalization or improvement of myocardial perfusion in the majority of patients with reversible and fixed perfusion defects by 201Tl scintigraphy. However, surgery may result in myocardial injury and scarring, with consequent decreased left ventricular ejection fraction in some patients.

Genetics, pathophysiology, and prognosis of hypertrophic cardiomyopathy

The definition of cardiomyopathies as idiopathic heart muscle disorders and their classification based on anatomy (hypertrophic and dilated) and physiology (restrictive) have underscored our ignorance of etiology and pathophysiology over the past decade. The localization of the disease locus to a site on chromosome 14 in two families and the subsequent demonstration of two unique mutations in the DNA encoding myosin heavy chain signal the beginning of the application of molecular biology techniques and ultimately of a molecular classification for hypertrophic cardiomyopathy. Unexplained left ventricular hypertrophy is the characteristic clinical feature and current prerequisite for the diagnosis. The severity and distribution of left ventricular hypertrophy are readily assessable with two-dimensional echocardiography and are associated with symptoms (ischemia, the finding of supraventricular and ventricular arrhythmias on Holter monitoring, and sudden death). Recent studies, however, suggest that radionuclide and echocardiographic measurements of diastolic abnormalities are independent of the magnitude of left ventricular hypertrophy. The major problem in management remains the prevention of sudden death. Routine cardiologic assessment fails to identify the majority of young patients who will die suddenly. Risk factor stratification, which may help determine potential mechanisms of sudden death, particularly in the young, is warranted.

Simultaneous occurrence of mitral valve prolapse and systolic anterior motion in hypertrophic cardiomyopathy

This report describes the simultaneous occurrence of mitral Valve prolapse (MVP) and systolic anterior motion (SAM) in hypertrophic cardiomyopathy (HC). In 25 patients (aged 7 to 62 years, mean 29), 15 (60%) of whom were male, distal portions of the anterior or posterior mitral leaflets approached or made midsystolic contact with the ventricular septum, whereas the proximal portion of the mitral leaflets showed marked cephalad excursion into the left atrium, 5 to 15 mm beyond the mitral anular plane. Three mitral valves that were available for gross visual inspection were not morphologically typical of patients with primary MVP. Clinical features and natural history (1 to 14 years [mean 6] of follow-up), cardiac dimensions, and distribution of left ventricular hypertrophy defined in the study patients did not appear to differ distinctly from those in the overall referral population of patients with HC evaluated at our institution. Hence, patients with HC may show a striking pattern of mitral valvular motion involving SAM into the left ventricular outflow tract, as well as MVP; this prolapse motion is probably due to anatomic disproportion between the mitral valve and the small left ventricular cavity rather than to the coexistence of 2 separate disease entities. Such patients further define the great diversity evident within the broad clinical spectrum of HC.

Absence of progression of left ventricular hypertrophy in adult patients with hypertrophic cardiomyopathy

Development or progression of left ventricular hypertrophy has recently been described in children with hypertrophic cardiomyopathy. To determine whether similar changes in magnitude and distribution of left ventricular hypertrophy may also occur in adult patients with this disease, serial assessment of left ventricular wall thickness was obtained with M-mode and two-dimensional echocardiography in 65 patients with hypertrophic cardiomyopathy who were 23 to 50 years of age. The follow-up period was 3 to 6 years (mean 4). None of the 65 patients showed a substantial increase (greater than or equal to 5 mm) in left ventricular wall thickness; however, 9 (14%) demonstrated a substantial decrease (5 to 9 mm). Wall thinning most commonly involved the anterior ventricular septum (seven patients), but was also identified in the posterior septum (six patients), lateral free wall (two patients) and posterior free wall (one patient). In the nine patients with wall thinning, left ventricular end-diastolic diameter increased significantly (from 44 +/- 6 to 51 +/- 6 mm; p less than 0.001); however, in seven of the nine, absolute cavity size remained within normal limits (less than or equal to 52 mm) at the most recent evaluation. Eight of the nine patients with left ventricular wall thinning and relative cavity enlargement were severely symptomatic and one was mildly symptomatic. In conclusion, substantial progression of left ventricular hypertrophy was not identified in any of the study patients. Hence, if such progression occurs in adults with hypertrophic cardiomyopathy, it is probably rare. Conversely, an important minority of adult patients with hypertrophic cardiomyopathy may show progressive left ventricular wall thinning and relative cavity enlargement, which are usually associated with severe cardiac symptoms.