Ultrastructural findings in endomyocardial biopsy of patients with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is clinically defined by progressive external ophthalmoplegia, atypical retinitis pigmentosa and the potential occurrence of complete atrioventricular (AV) block. Right septal endomyocardial biopsy specimens from nine patients (four men and five women with a mean [+/- SD] [corrected] age of 36.3 +/- 14.4 years) with chronic progressive external ophthalmoplegia and mitochondrial skeletal myopathy were studied. Three patients had atypical retinal pigmentation. An atrioventricular or intraventricular conduction defect was observed in five patients. A pacemaker was prophylactically implanted in one patient because of abnormal conduction distal to the His bundle. Ultrastructural investigations revealed mitochondriosis in many heart muscle cells and an increased variability of mitochondrial form and size in all patients. In seven patients, 0.4 to 2.1% of all examined myocytes contained exclusively abnormal mitochondria. Three main types were observed: huge, mainly round mitochondria with concentric cristae; large, round or oval mitochondria with transverse or curved cristae; and small, vacuolated mitochondria. The volume density of myofibrils was reduced (41.9 +/- 11.1 compared with the normal value of 56.5 +/- 2.5 volume density [in percent], p less than 0.01) in these myocytes. Increasing numbers of vacuolated mitochondria correlated significantly with a reduction of myofibrils (r = -0.64, p less than 0.01). The data suggest that the ventricular myocardium of most patients with complete and even incomplete Kearns-Sayre syndrome is affected by disseminated mitochondrial cytopathy.

Prediction of the site and severity of obstruction in hypertrophic cardiomyopathy by color flow mapping and continuous wave Doppler echocardiography.

OBJECTIVE: We investigated whether the site and severity of an obstruction in hypertrophic cardiomyopathy can be accurately predicted by the combined use of color-coded and continuous wave Doppler echocardiography. BACKGROUND: Predicting the site of obstruction by end-systolic cavity shape is not reliable. Therefore, hemodynamic localization of the obstruction is required before surgery is performed. Such localization should be possible with color flow imaging, which provides two-dimensional velocity mapping reflecting the distribution of pressures within the left ventricle. Discrepancies in assessment of the pressure gradient by Doppler echocardiography and cardiac catheterization (which are usually not performed simultaneously) may be due to spontaneous variation of the dynamic obstruction in addition to technical factors related to both methods. METHODS: Twenty consecutive patients with hypertrophic cardiomyopathy were examined 1 day before transseptal left heart catheterization. The obstruction site was defined by color flow mapping. The pressure gradient was determined by continuous wave Doppler echocardiography. Measurements were also performed simultaneously in 10 patients during cardiac catheterization. RESULTS: Midventricular obstruction was correctly identified in 4 patients and subvalvular obstruction in 15 patients. One patient had no obstruction at rest. Invasively and noninvasively determined pressure gradients correlated well (r = 0.89, SEE = 16.3 mm Hg). Multiple single-beat analysis in 10 patients, also simultaneously examined with Doppler echocardiography and catheterization, yielded an excellent correlation (r = 0.97, SEE = 13.1 mm Hg). Comparing the simultaneous (r = 0.96, SEE = 12.5 mm Hg) and nonsimultaneous (r = 0.81, SEE = 23.8 mm Hg) recordings in these patients, we found that the spontaneous variation of the dynamic obstruction mainly accounted for discrepancies (p less than 0.05). CONCLUSION: The combined use of color-coded and continuous wave Doppler echocardiography provides the relevant hemodynamic information required for decision-making in patients with hypertrophic cardiomyopathy who are considered for transaortic myectomy.

Increased risk of bacterial endocarditis in inflammatory bowel disease.

PURPOSE: The purpose of this retrospective as well as prospective case-control study was to analyze a possible overrepresentation of inflammatory bowel diseases among patients with native valve endocarditis as well as the factors that predispose patients with inflammatory bowel disease to infective endocarditis. PATIENTS AND METHODS: Among 213 consecutive patients treated for proven native valve endocarditis, six (2.8%) had inflammatory bowel diseases (three with ulcerative colitis and three with Crohn's disease). Three patients with inflammatory bowel disease were from the retrospective group, and three were from the prospective group. The prevalence of inflammatory bowel diseases has been determined to be 0.0641% in the Düsseldorf area. RESULTS: On the basis of these data, a 44-fold overrepresentation of inflammatory bowel diseases among the 213 patients with endocarditis was calculated with a statistical significance of p much less than 0.001. CONCLUSIONS: Inflammatory bowel disease may be considered an independent risk factor for bacterial endocarditis. Reasons may be more frequent bacteremias as a result of the higher incidence of diagnostic and therapeutic interventions, as well as increased permeability of the damaged mucosa for bacteria and the therapeutic immunosuppression in patients with active inflammatory bowel disease. Prophylaxis for bacterial endocarditis should be carefully considered before expected bacteremias in patients with highly active inflammatory bowel disease even in the absence of cardiac factors predisposing to bacterial endocarditis.

Myocardial imaging and metabolic studies with [17-123I]iodoheptadecanoic acid in patients with idiopathic congestive cardiomyopathy.

In twenty patients with primary congestive cardiomyopathy (COCM) the patterns of accumulation and washout of the fatty acid analogue [17-123I]iodoheptadecanoic acid (I-123 HA) were studied. In contrast to patients with ischemic heart disease, where reduced I-123 HA accumulation was correlated with stenosis of the main coronary arteries, thus usually involving larger wall segments, the patients with COCM concentrated I-123 HA heterogeneously in small spotty segments throughout the entire left-ventricular myocardium. The regional washout half-times varied between 15.1 and 116.2 min. It seems that in patients with severe COCM the elimination half-times are more prolonged than in early stages of the disease. There was no correlation between the regional uptake and the elimination half-times. Sequential myocardial imaging with I-123 HA appears useful for noninvasively diagnosis of COCM.

Tracer kinetics of 15-(ortho-123/131I-phenyl)-pentadecanoic acid (oPPA) and 15-(para-123/131I-phenyl)-pentadecanoic acid (pPPA) in animals and man.

The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta-oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double-labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle.

Doppler echocardiographic assessment of the pressure gradient during bicycle ergometry in hypertrophic cardiomyopathy.

To assess the behavior of the subvalvular pressure gradient under physical exercise, 13 patients with obstructive hypertrophic cardiomyopathy were examined during upright bicycle ergometry by means of Doppler echocardiography. Additionally, right-sided cardiac catheterization was performed within 7 days. In 10 patients adequate Doppler tracings could be obtained during exercise. The Doppler-derived systolic pressure gradient increased from 75 +/- 24 to 140 +/- 42 mm Hg (p less than 0.0005). This was associated with an increase in the duration of the systolic mitral-septal contact from 59 +/- 21 to 136 +/- 28 ms (p less than 0.0005). Correlation between the pressure gradient and the duration of mitral-septal contact at rest and during exercise was good (r = 0.86), whereas correlation between the resting and exercise pressure gradient (r = 0.34) did not reach statistical significance. The increase in stroke volume during exercise, from 90 +/- 18 to 95 +/- 24 ml, was significant (p less than 0.05) but minimal. Therefore, only a moderate increase in systolic flow, from 205 +/- 54 to 268 +/- 78 ml/s (p less than 0.0005), was observed. Outflow tract resistance, defined as the ratio of the pressure gradient to systolic flow, increased from 0.38 +/- 0.11 to 0.57 +/- 0.24 mm Hg.s/ml (p less than 0.01). Thus, in a selected group of patients with hypertrophic cardiomyopathy a substantial increase in the maximal pressure gradient during upright bicycle ergometry was demonstrated in most patients. Exercise Doppler echocardiography may be valuable to assess the hemodynamic significance of obstruction in individual patients in a physiologic setting and has a potential to monitor the effect of therapeutic interventions.

Internal thoracic artery: prevalence of atherosclerotic changes.

Use of the internal thoracic artery for myocardial revascularization has regained general acceptance because it offers better long-term results than do venous conduits. The aim of this study was to ascertain the prevalence of atherosclerosis in the internal thoracic artery and to correlate the prevalence with other known risk factors. A total of 117 patients (male/female ratio 84:33; mean age 56.8 years) were investigated. Sixty-eight patients had coronary artery disease, 25 had combined coronary artery and valvular heart disease, 14 had acquired valvular heart disease, and 10 had other types of heart disease. All but one patient underwent bilateral semiselective internal thoracic arteriography. Evidence of atherosclerotic change was present in 6.6% of the opacified vessels in 11.1% of the investigated individuals. Although all patients with atherosclerotic lesions in the internal thoracic artery had coronary artery disease, no correlation could be found between coronary artery disease and internal thoracic atherosclerosis. Peripheral vascular disease and hyperlipidemia could be identified as predictors of atherosclerotic changes in the internal thoracic artery. Atherosclerosis is somewhat more prevalent in the internal thoracic artery in this study than in the literature. Although the internal thoracic artery is a protected vessel, there is a certain extent of atherosclerosis, that correlates with known risk factors. Our observations should not preclude use of the internal thoracic artery, but they should be considered for patients who are at risk for atherosclerotic changes of the internal thoracic artery.

Duplex sonography of the internal thoracic artery. Preoperative assessment.

Ultrasonic duplex scanning was used to examine 211 internal thoracic arteries. The investigating vessels were classified as normal, abnormal, and occluded. The results of the duplex examination were compared with angiography as the reference method. The diameter measurements showed virtually no differences between the two methods. Normal internal thoracic arteries showed a continuous decrease of the systolic flow velocities from proximal to distal and a narrow to moderate spectral flow curve, whereas arteries classified as abnormal showed a velocity profile distinct from that--in particular, no decrease of the systolic peak velocities and an increased spectral broadening during systole with peak frequencies greater than 4 kHz at 60 degrees (> 1.2 m/sec). In occluded vessels no flow could be detected. The majority of changes were found in the proximal part of the internal thoracic artery. All lesions were detected by duplex sonography. Six normal vessels were misjudged as abnormal by the duplex method. The sensitivity, specificity, and accuracy of duplex sonography compared with angiography as the reference method were 100% (95% CI, 74.4% to 100%), 96.9% (95% CI, 93.2% to 98.8%), and 97.2% (95% CI, 93.6% to 98.8%), respectively. Duplex sonography is a reliable, noninvasive technique for the preoperative assessment of the internal thoracic artery. It allows the detection of potential atherosclerotic changes in the internal thoracic artery and the assessment of adequacy of caliber and flow.

Cardiac amyloid deposits in endomyocardial biopsies. Light microscopic, ultrastructural, and immunohistochemical studies.

In four patients with unexplained, abnormal thickening of the interventricular septum as demonstrated by echocardiography, right ventricular endomyocardial biopsy revealed unexpected cardiac amyloid deposits that resulted in increased myocardial thickness and rapidly progressive heart failure. Light microscopically, amyloid was observed in the subendocardial layer, interstitium, and walls of the intramural arterioles. Electron-microscopically, the amyloid fibrils were adjacent to the basement membranes of the heart muscle cells and the vascular smooth muscle cells. Immunohistochemical typing with specific antibodies against different amyloid fibril proteins on glutaraldehyde-fixed paraffin sections revealed different amyloid types. In two patients with generalized idiopathic amyloidosis and in two others with amyloidosis in multiple myeloma, the A-lambda form was diagnosed. In a fifth patient, AA-amyloidosis was found in familial Mediterranean fever with cardiac manifestation without thickening of the interventricular septum. The amyloid deposits were located almost exclusively within the walls of the myocardial arterioles. The amount of amyloid as observed in the myocardial biopsies correlates with the rapidly progressive cardiac failure. It is suggested that in patients with abnormal thickening of the interventricular septum of unknown origin the diagnosis should be clarified by endomyocardial biopsy.

Hemodynamic findings in patients with left bundle branch block after myectomy in hypertrophic obstructive cardiomyopathy (HOCM)

To determine the hemodynamic effects of postoperative left bundle branch block (LBBB) in patients with hypertrophic obstructive cardiomyopathy (HOCM), we investigated 28 patients using Swan-Ganz pulmonary artery catheterization at rest and on exercise. Fourteen patients had postoperative LBBB (group A) and 14 had undisturbed intraventricular conduction (group B). All patients were examined by clinical investigation, electrocardiogram and bicycle ergometer exercise preoperatively and postoperatively (mean 6 months). Pulmonary artery pressure and pulmonary capillary wedge pressure were continuously measured, stroke volume index and cardiac index were obtained by the thermodilution method. All patients showed an improvement of their clinical symptoms (NYHA class: 2.8 +/- 0.45 before and 1.7 +/- 0.22 after operation) (P < 0.05). The postoperative exercise capacity (Watt) increased significantly (P < 0.05) in group A by 38% and in group B by 30%. The maximum mean pulmonary artery pressure on physical exercise decreased in group A from 40.7 +/- 9.1 to 32.5 +/- 8.7 mmHg and in group B from 42.8 +/- 12.4 to 32.4 +/- 9.2 mmHg (P < 0.05). The maximal stroke volume index and cardiac index improved significantly in 9 of 14 patients in each group. Thus, patients with HOCM and LBBB after myectomy have a marked improvement in postoperative hemodynamics, the results equaling those of patients with undisturbed intraventricular conduction.

Semi-quantitative analysis of SPECT with the iodinated fatty acid 15-(ortho-123I-phenyl)-pentadecanoic acid.

15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA) in contrast to the para-isomer pPPA has a prolonged retention in the normal human myocardium. Following qualitative evaluation, a semi-quantitative analysis of oPPA-SPECT is presented in 52 patients (41 with coronary artery disease (CAD) and 11 normals). Data were compared to the results of coronary angiography (CAD patients). Up to 220 MBq 123I-labelled oPPA were injected intravenously after overnight fasting and bicycle exercise. Four minutes later SPECT acquisition (180 degrees technique) was started. In 15 patients a second dose of oPPA was injected 2.5 h later and the study was repeated under rest conditions. Compared to our qualitative analysis the semi-quantitative approach revealed a lower sensitivity of 76% for the detection of CAD (global, stenoses greater than 50%) (specificity was not analysed because the normal patients served as the control group for the calculation of normal values). Because the sensitivity does not exceed that of 201Tl-SPECT or MIBI-SPECT, oPPA is not recommended for the detection of CAD, but it may serve for the evaluation of myocardial viability in ischaemic regions.

15-(ortho-123I-phenyl)-pentadecanoic acid, a new myocardial imaging agent for clinical use.

The result of previous experiments in rodents indicated different kinetics for the para- and ortho-isomers of 15-(iodophenyl)-pentadecanoic acid (p-IPPA, o-IPPA), with o-IPPA showing an enhanced rate of washout. To test the relevance of this phenomenon for clinical diagnosis, 15 fasting male patients with confirmed coronary heart disease (1-VD/7, 2-VD/4, 3-VD/4) were investigated under exercise. Serial images were recorded at a rate of 3 frames min-1 for 70 to 90 min, corrected for tracer in blood and compared with thallium-201 images obtained from these patients within less than 2 weeks. Time-activity curves were also taken from the peripheral blood. Ortho-IPPA was well taken up by healthy myocardium and, contrary to rodents, retained with elimination half times longer than 200 min. A decreased myocardial uptake was seen which was very similar to the pattern obtained with thallium. Ortho-IPPA was eliminated from the blood to less than 10% at 4 min. Almost all radioactivity was in the organic phase (greater than 95% at 5 min) and chromatography showed only one major peak (o-IPPA) indicative of minimal organic catabolism.

Indications and selection criteria for cardiac transplantation.

Assessment of indications for cardiac transplantation is a complex process including first a comparison of expected survival of a patient with end-stage heart disease, mostly ischemic or dilative cardiomyopathy, allocated either to conventional medical or surgical therapy or to cardiac transplantation, second the expected increase in exercise tolerance and quality of life after transplantation. Furthermore the exclusion of contraindications is required: severe irreversible secondary organ damage (especially of kidneys and liver), malignant tumors and systemic malignancies, severe pulmonary hypertension, florid infections, unstable psychosocial conditions of the patient and his surrounding. Although a considerable number of clinical, electrocardiographic, echocardiographic and hemodynamic factors have been defined as indicating very poor prognosis, there exists no prognostic index combining all these factors into a precise prediction of survival of an individual patient with end-stage cardiac failure. Whereas high survival rates have been concordantly documented for the first years after transplantation, the long-term prognosis cannot be estimated as yet with equally sufficient certainty, due to increasing observation of vasculopathies and of progressive myocardial (mostly diastolic) dysfunction of transplanted hearts. These problems suggest to continue with very careful selection of candidates for transplantation. Even in the case of cardiac decompensation and poor prognostic factors, usually a single examination of the patient is not sufficient, but rather a thorough observation of the patient over a period of time including an evaluation of the rate of clinical and hemodynamic decline and of the response to medical therapy.

[Simultaneous measurement of indirect (Doppler-ultrasonic-technique) and direct arterial systolic blood pressure of the human radial artery (author's transl)]. / Simultane Messungen des systolischen Blutdruckes mit der Ultraschall-Doppler-Technik und der blutigen Methode an der Arteria radialis des Menschen.

At 28 subjects without arterial occlusive disease, the systolic blood pressure of the radial artery was recorded simultaneously by means of the Doppler Ultrasonic Auscultatory Method (Doppler Ultrasonic Wall Motion Technique) and by intraarterial needle and strain-gauge manometer, and the results were compared. In the overall collective the mean values of the systolic pressure were nearly identical (139.6 and 139.7 mm Hg). This applies also to the standard deviation (+/- 19,9 and +/- 19,4). The correlation coefficient was 0.90. These results point to the validity of the indirect measurement of the peripheral systolic pressure by means of the Ultrasonic Doppler Technique. However, there must be taken into consideration that in a particular case there can arise a larger deviation at normal arteria. Possibilities of technical errors at the blood pressure recorded by intraarterial needle and strain-gauge manometer as well as on determining the blood pressure with compression method will be considered. It is concluded that Doppler Method provides a sensitive and accurate noninvasive approach for measurement of peripheral systolic arterial pressure.

[Exercise studies in patients with cardiomyopathy (author's transl)]. / Belastungsuntersuchungen bei Patienten mit Kardiomyopathie.

Exercise tests were performed on 50 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 19 patients with hypertrophic nonobstructive cardiomyopathy (HNCM) of NYHA classes I to IV, and on 16 patients with congestive cardiomyopathy (CCM) of NYHA classes III and IV as well as, for detection of latent cardiomyopathy (LCM), i.e. functional impairment during exercise with normal findings at rest, on 102 patients with typical or atypical angina pectoris and ECG abnormalities of unknown etiology (left bundle branch block or ST segment depression) but normal coronary arteries and normal left and right ventriculogram. Measurements included heart rate, stroke volume, cardiac output, pulmonary artery pressure and minimal cardiac transit times of Indium-113m. Furthermore, in a large number of patients with latent cardiomyopathy, thallium-201 myocardial imaging and measurements of myocardial lactate extraction during high-rate atrial pacing were performed. The findings suggest that 1. the functional classification based on the patients' complaints often differs from the grade of hemodynamic impairment detected by exercise testing, 2. therapeutic effects (propranolol or surgery in HOCM, prazosin in CCM) are more pronounced under exercise as compared with resting conditions. Latent cardiomyopathy can be diagnosed only by detection of impaired function during exercise (increased pulmonary artery pressure, impaired myocardial lactate extraction during high-rate stimulation), since ventricular function and hemodynamics are normal at rest.

[Complications of an idiopathic rhabdomyolysis (Meyer-Betz syndrome) after physical exertion]. / Komplikationen einer idiopathischen Rhabdomyolyse (Meyer-Betz-Syndrom) nach körperlicher Belastung.

A few hours after a 15 km march a 19-year-old man developed a fever of 40 degrees C, accompanied by hemoptysis, tarry stools and pain in the thigh. On physical examination there was tenderness and swelling over the shoulders, upper arms and thighs as well as petechiae, bruises, hepatomegaly, pain on percussion over the kidney region and signs of hypovolaemia. There was leukocytosis (18,800/microliters) and increased creatinase activity (3900 U/l, rising to 66,300 U/l after 24 h). The platelet count fell from 147,000 to 11,000/microliters, the fibrinogen level to 0.25 milligrams. On the second day serum creatinine was 4.1 mg/dl, urine volume 50 ml/24 h, urinary myoglobin concentration 120,000 micrograms/l. The Quick value dropped to under 3%, while liver enzymes and bilirubin concentration rose. The rhabdomyolysis caused acute respiratory failure, despite symptomatic treatment of the acute renal failure and consumption coagulopathy, but after 8 weeks of intensive treatment the patient was discharged without symptoms. No cause other than the preceding physical exertion was found for the rhabdomyolysis. Muscle biopsy revealed unspecific changes 4 1/2 months after discharge.