Heinrich G. Klues

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

OBJECTIVES This study sought to achieve an understanding of the true structural heterogeneity of hypertrophic cardiomyopathy. BACKGROUND The diversity and clinical significance of the morphologic expression of hypertrophic cardiomyopathy have not been fully defined within this broad disease spectrum. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy.

BackgroundHypertrophic cardiomyopathy (HCM) is characterized by an asymmetrically hypertrophied left ventricle and is regarded as a disease of cardiac muscle. Methods and ResultsTo assess the possibility that the mitral valve itself may be involved in the disease process, we studied mitral valves from 94 patients with HCM and 45 normal control subjects. The area of the mitral leaflets was increased in patients with HCM compared with control subjects (12.9±3.7 versus 8.7±2.0 cm2; p<0.001). For the overall group of patients, this increase was largely caused by an increase in anterior leaflet length (2.2 ±0.5 cm for HCM versus 1.8±0.3 cm for control subjects; p <0.001), because circumference did not differ between the two groups. Mitral leaflet area was increased (.12.0 cm2) in 55 58%) of the 94 valves. In 12 of these 55 valves, both the anterior and posterior leaflets were enlarged; the other 43 valves had asymmetrical or segmental enlargement of either the anterior leaflet (36 patients) or portion of posterior leaflet (seven patients). In addition, nine patients had a congenital malformation of the mitral apparatus in which one or both papillary muscles inserted directly into anterior mitral leaflet mitral valve area was normal in seven of the nine). ConclusionsSixty-two (66%) of 94 mitral valves had a constellation of structural malformations, including increased leaflet area and elongation of the leaflets or anomalous papillary muscle insertion directly into anterior mitral leaflet. These findings expand the morphological definition of HCM by demonstrating that the disease process is not confined to cardiac muscle but rather many patients also have structural abnormalities of the mitral valve that are unlikely to be acquired or secondary to mechanical factors.

Functional, angiographic and intracoronary doppler flow characteristics in symptomatic patients with myocardial bridging: Effect of short-term intravenous beta-blocker medication

OBJECTIVES We sought to define the effects of short-term beta-adrenergic blocking medication on intracoronary flow characteristics, clinical symptoms and angiographic diameter changes in patients with severe myocardial bridging of the left anterior descending coronary artery. BACKGROUND Controversy exists regarding the pathophysiology, clinical relevance and optimal therapy in symptomatic patients with myocardial bridges because antianginal drugs have not been systematically tested. METHODS In 15 symptomatic patients with myocardial bridging of the left anterior descending coronary artery, maximal lumen diameter reductions were evaluated by quantitative coronary angiography. There were no angiographic signs of coronary artery disease. Coronary blood flow velocities (using a 0.014-in. [0.035 cm] Doppler guide wire) were measured at rest, during atrial pacing and during intravenous administration of a short-acting beta-blocker (esmolol, 50 to 500 micrograms/kg body weight per min) with continuous atrial pacing. RESULTS The maximal angiographic systolic lumen diameter reduction within the myocardial bridges was 83 +/- 9% at rest, with a persistent diastolic diameter reduction of 41 +/- 11% (mean +/- SD). Short-term intravenous beta-blocker therapy decreased the diameter reduction during both systole (from 83 +/- 9% to 62 +/- 11%) and diastole (from 41 +/- 11% to 30 +/- 9%, both p < 0.001). The average diastolic peak flow velocity was higher within the myocardial bridges (33 +/- 13 cm/s) than the proximal (26 +/- 13 cm/s) and distal bridges (17 +/- 4 cm/s, both p < 0.001). During tachypacing, average diastolic peak flow velocity increased within the bridged segments to 63 +/- 21 cm/s versus 29 +/- 12 cm/s in the proximal and 20 +/- 4 cm/s in the distal bridges (both p < 0.001). Beta-receptor blockade produced a return to baseline values (average diastolic peak flow velocity within bridge 35 +/- 16 cm/s, p < 0.001). ST segment changes and symptoms were abolished with beta-blocker administration. CONCLUSIONS In patients with myocardial bridges, administration of short-acting beta-blockers during atrial pacing alleviates anginal symptoms and signs of ischemia. This effect was mediated by a reduction of vascular compression and maximal flow velocities within the bridged coronary artery segment.

Anomalous insertion of papillary muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy. Significance in producing left ventricular outflow obstruction.

BackgroundObstruction to left ventricular outflow in hypertrophic cardiomyopathy (HCM) is usually due to systolic anterior motion of the mitral valve. Occurrence of structural mitral valve abnormalities in HCM and their significance in producing outflow obstruction (even in the absence of typical systolic anterior motion) has not been fully appreciated. Methods and ResultsAnalysis of 78 mitral valves excised from patients with obstructive HCM showed that 10 (13%) had anomalous insertion of one or both left ventricular papillary muscles directly into the anterior mitral leaflet. This malformation was identified by echocardiography, which demonstrated direct continuity between the hypertrophied papillary muscle and mitral leaflet, resulting in a long rigid area of midcavity narrowing that appeared to be solely or largely responsible for outflow obstruction. Basal subaortic pressure gradients were large (70–150 mm Hg). Mitral valve replacement reduced the outflow gradient substantially to 0–15 mm Hg in four patients with postoperative cardiac catheterization. However, two other patients who underwent septal myotomy/myectomy had persistent symptoms and incomplete relief of obstruction (gradients 60 and 70 mm Hg) because of continued midcavity apposition of papillary muscle and ventricular septum. ConclusionsAnomalous papillary muscle insertion into anterior mitral leaflet represents a mechanism of obstruction to left ventricular outflow in patients with HCM and differs considerably from typical dynamic obstruction caused by mitral valve systolic anterior motion that occurs in many other patients with HCM. Recognition of this malformation emphasizes the diverse morphological expression of HCM and also has important clinical implications for patients requiring operation because the gradient is likely to persist even after adequate myotomy/myectomy; consequently, mitral valve replacement would appear to be the operation of choice in most such patients.

Disturbed Intracoronary Hemodynamics in Myocardial Bridging Early Normalization by Intracoronary Stent Placement

BACKGROUND The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.

Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy.

BackgroundThe morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularl the contribution of mitral leaflet length and size. Methods and ResultsTo clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area < 12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area >12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3±1.0 versus 1.9±0.7 cm2 for normal-sized valves; p<0.001) and also had greater systolic excursion of the anterior leaflet (16.2±4.5 versus 13.3±3.3 mm, p<0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum (“typical” SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae (“atypical” SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening. ConclusionsPatients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening.

Influence of a platelet GPIIb/IIIa receptor antagonist on myocardial hypoperfusion during rotational atherectomy as assessed by myocardial Tc-99m sestamibi scintigraphy

OBJECTIVES This study evaluated the effect of the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist abciximab on myocardial hypoperfusion during percutaneous transluminal rotational atherectomy (PTRA). BACKGROUND PTRA may cause transient ischemia and periprocedural myocardial injury. A platelet-dependent risk of non-Q-wave infarctions after directional atherectomy has been described. The role of platelets for the incidence and severity of myocardial hypoperfusion during PTRA is unknown. METHODS Seventy-five consecutive patients with complex lesions were studied using resting Tc-99m sestamibi single-photon emission computed tomography prior to PTRA, during, and 2 days after the procedure. The last 30 patients received periprocedural abciximab (group A) and their results were compared to the remaining 45 patients (group B). For semiquantitative analysis, myocardial perfusion in 24 left ventricular regions was expressed as percentage of maximal sestamibi uptake. RESULTS Baseline characteristics did not differ between the groups. Transient perfusion defects were observed in 39/45 (87%) patients of group B, but only in 10/30 (33%) patients of group A (p < 0.001). Perfusion was significantly reduced during PTRA in 3.3 +/- 2.5 regions in group B compared to 1.4 +/- 2.5 regions in group A (p < 0.01). Perfusion in the region with maximal reduction during PTRA in groups B and A was 76 +/- 15% and 76 +/- 15% at baseline, decreased to 56 +/- 16% (p < 0.001) and 67 +/- 14%, respectively, during PTRA (p < 0.01 A vs. B), and returned to 76 +/- 15% and 80 +/- 13%, respectively, after PTRA. Nine patients in group B (20%) and two patients in group A (7%) had mild creatine kinase and/or troponin t elevations (p = 0.18). Patients with elevated enzymes had larger perfusion defects than did patients without myocardial injury (4.2 +/- 2.7 vs. 2.3 +/- 2.5 regions, p < 0.05). CONCLUSIONS These data indicate that GPIIb/IIIa blockade reduces incidence, extent and severity of transient hypoperfusion during PTRA. Thus, platelet aggregation may play an important role for PTRA-induced hypoperfusion.

Coexistence of sudden cardiac death and end-stage heart failure in familial hypertrophic cardiomyopathy

OBJECTIVES The purpose of this study was to determine the occurrence of sudden cardiac death or end-stage heart failure, two phases of the natural history of hypertrophic cardiomyopathy, in closely related relatives. BACKGROUND Hypertrophic cardiomyopathy is a genetically transmitted cardiac disease with a particularly diverse clinical and morphologic spectrum. Premature death usually occurs either suddenly or as a result of progressive congestive heart failure. METHODS We describe seven families with genetically transmitted hypertrophic cardiomyopathy that were studied with echocardiography or necropsy, or both, and were selected because they were known to include relatives who had incurred either premature sudden cardiac death or the end-stage phase of the disease. RESULTS The seven families comprised 128 relatives; 26 died suddenly, and 9 developed end-stage heart failure (including 2 with heart transplantation) associated with left ventricular cavity enlargement, wall thinning or decreased contractility, alone or in combination, as well as loss of outflow obstruction. Patients who died suddenly did so at younger ages (23 +/- 10 years) than did patients who died or required heart transplantation in the end-stage phase of hypertrophic cardiomyopathy (42 +/- 8 years, p < 0.001). CONCLUSIONS This study demonstrates that family members with hypertrophic cardiomyopathy, despite a common genetic substrate, may exhibit markedly diverse and distinct expressions of the natural history of their disease, which occur at widely separated periods of life.

Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy : increase in gradient after exercise

To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/- 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation.

Congenital quadricuspid aortic valve anomaly associated with hypertrophic non-obstructive cardiomyopathy: a case report and review of the literature.

A case is reported of a 38 year old woman without known cardiac congenital abnormality but a history of well controlled arterial hypertension who was admitted to hospital after successful resuscitation at home following cardiac arrest. There was no evidence of myocardial infarction on 12-lead electrocardiogram but there were signs of left ventricular hypertrophy. Transoesophageal echocardiography revealed a rare quadricuspid aortic valve (QAV) malformation with concomitant mild aortic regurgitation. The left ventricle showed a massive concentric hypertrophy without obstruction. The patient was eventually transferred in a persistent vegetative state to a home care facility. A review of the literature revealed 70 cases of QAV diagnosed by transthoracic or transoesophageal echocardiography (26 cases), at necropsy (25), during surgery (15), and during angiography (4). The present case is the first report of QAV associated with non-obstructive hypertrophic cardiomyopathy.