B. Schwartzkopff

Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension.

BACKGROUND In hypertensive patients with angina pectoris, the coronary vasodilator reserve is frequently impaired despite a normal coronary angiogram. Experimental data indicate that structural alterations of the intramyocardial coronary vasculature contribute to an increased minimal coronary resistance and a diminished coronary flow reserve. METHODS AND RESULTS In 14 patients (10 men and 4 women) with arterial hypertension and 8 normotensive subjects, minimal coronary resistance and vasodilator reserve (dipyridamole: 0.5 mg/kg body wt, gas chromatographic argon method) were determined after the angiographic exclusion of relevant coronary artery disease. Coronary reserve was depressed in hypertensive patients (2.7 +/- 2.3 vs 4.6 +/- 1.3, P < or = .05) due to increased minimal coronary resistance (0.64 +/- 30 vs 0.24 +/- 0.055 mm Hg.min.100 g.mL-1, p < or = 0.002). In right septal biopsies, mean external arteriolar diameter (21.6 +/- 2.3 vs 17.2 +/- 2.5 microns, P < or = .001), mean arteriolar wall area (271 +/- 61 vs 172 +/- 62 microns 2, P < or = .01), percent medial wall area (69.9 +/- 4.0 vs 66.0 +/- 3.2%W, P < or = .05), mean periarteriolar fibrosis area (216 +/- 122 vs 104 +/- 68 microns 2, P < or = .05), and volume density of total interstitial fibrosis (3.6 +/- 1.8 vs 1.9 +/- 0.5Vv% fibrosis, P < or = .05) were increased in hypertensive patients compared with normotensive subjects. Minimal coronary resistance correlated with %W (r = .6, P < or = .003) and Vv% fibrosis (r = .62, P < or = .002). Left ventricular mass index (111 +/- 21 vs 97 +/- 17 g/m2, P = NS) and left ventricular end-diastolic pressure (12 +/- 6 vs 8 +/- 3 mm Hg, P = NS) did not correlate significantly with minimal coronary resistance. In multivariate analysis, both %W and Vv% fibrosis explained half of the variability of minimal coronary resistance (r2 = .5, P < or = .002). CONCLUSIONS Structural remodeling of the intramyocardial coronary arterioles and the accumulation of fibrillar collagen are decisive factors for a reduced coronary dilatory capacity in patients with arterial hypertension and angina pectoris in the absence of relevant coronary artery stenoses.

Repair of Coronary Arterioles After Treatment With Perindopril in Hypertensive Heart Disease

In hypertensive heart disease, no data are available on the repair of coronary resistance vessels in patients after long-term ACE inhibitor treatment. Fourteen patients with essential hypertension were studied with coronary flow reserve and with transvenous endomyocardial biopsy before and after 12 months of antihypertensive treatment with perindopril (4 to 8 mg/d, mean 5.9+/-2.3 mg/d). Left ventricular muscle mass index decreased by 11% (from 145+/-41 to 128+/-36 g/m(2), P=0.04). Maximal coronary blood flow was increased by 54% (from 170+/-46 to 263+/-142 mL. min(-1). 100 g(-1), P=0.001), and minimal coronary vascular resistance was diminished by 33% (from 0.67+/-0.21 to 0.45+/-0.19 mm Hg. min. 100 g. mL(-1), P=0.001); consequently, coronary reserve increased by 67% from 2.1+/-0.6 to 3. 5+/-1.9 (P=0.001). Structural analysis revealed regression of periarteriolar collagen area by 54% (from 558+/-270 to 260+/-173 microm(2), P=0.04) and of total interstitial collagen volume density by 22% (from 5.5+/-3.8 Vv% to 4.3+/-3.2 Vv%, P=0.04), whereas arteriolar wall area was slightly but not significantly reduced. Long-term therapy with the ACE inhibitor perindopril induces structural repair of coronary arterioles that is mainly characterized by the regression of periarteriolar fibrosis and associated with a marked improvement in coronary reserve. These findings indicate the beneficial reparative effects of ACE inhibition on coronary microcirculation in hypertensive heart disease.

Alterations of the Architecture of Subendocardial Arterioles in Patients With Hypertrophic Cardiomyopathy and Impaired Coronary Vasodilator Reserve: A Possible Cause for Myocardial Ischemia

OBJECTIVES The study was designed to investigate the architecture of subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and angina pectoris with respect to coronary vasodilator reserve. BACKGROUND There is growing evidence that the coronary microvasculature is abnormal in HCM. Arterioles, which mainly regulate intramyocardial blood flow, are especially suspect. METHODS Thirteen patients with HCM (50.1+/-12.6 years old, mean value +/- SD) were studied after exclusion of any relevant coronary stenoses. Subendocardial arterioles (density [n/mm2], wall area [microm2], percent lumen area [%lumen], periarteriolar collagen area [microm2]), myocyte diameter (microm) and interstitial collagen fraction (Vv%) were evaluated by means of stereologic morphometry of transvenous biopsy samples. Coronary blood flow was measured quantitatively with the inert chromatographic argon method at basal conditions and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and coronary vasodilator reserve was calculated as the ratio of coronary resistance at basal conditions and after pharmacologic vasodilation. Data from five normotensive subjects (45.4+/-11 years old, p = NS) served as control data. RESULTS Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13% (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve was impaired in patients with HCM (2.28+/-0.6 vs. 5.34+/-1.49, p = 0.003) because of higher coronary resistance after vasodilation (0.48+/-0.14 vs. 0.22+/-0.06 mm Hg x min x 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003). CONCLUSIONS In HCM, the architecture of preterminal subendocardial arterioles is altered by a reduced total cross-sectional lumen area, corresponding to an impaired coronary vasodilator capacity that may predispose to myocardial ischemia.

Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy.

Left ventricular (LV) dilation and myocardial remodelling are hallmarks of heart failure in idiopathic dilated cardiomyopathy (DCM). Interstitial collagen is essential for LV integrity and function while degradation of collagen by collagenases, especially matrix‐metalloproteinases (MMPs), are suggested to contribute to ventricular dilation. In the present study, serological markers of collagen metabolism were investigated.

Structural analysis of arteriolar and myocardial remodelling in the subendocardial region of patients with hypertensive heart disease and hypertrophic cardiomyopathy

Abstract Left ventricular hypertrophy is a risk factor for cardiovascular morbidity and mortality. In arterial hypertension and in hypertrophic cardiomyopathy it may be accompanied by clinical signs of myocardial ischaemia resulting from microcirculatory dysfunction in the absence of coronary macroangiopathy. Structural changes of the vascular and interstitial compartment of the heart are involved in the pathogenesis of impaired microcirculation. We investigated patients with hypertensive heart disease (HHD; n=12) and hypertrophic cardiomyopathy (HCM; n=19) without coronary macroangiopathy but with signs of myocardial ischaemia. Right septal endomyocardial biopsies were evaluated to quantify the structure of intramyocardial arterioles, collagen content and myocytic diameter by morphometric rules. Nine normotensive subjects served as controls. The groups differed significantly (P<0.05) in myocytic diameter and total collagen content. The myocytic diameter correlated with the thickness of the interventricular septum. Arterioles in HHD showed a significant increase in cross-sectional medial area and in HHD patients the periarteriolar collagen area increased both in absolute terms and when standardized to medial area. Arteriolar density was significantly reduced in HCM. In a multivariate discriminant analysis the positive predictive value for differentiation of the groups by non-myocytic variables was 72.5% (P=0.013). HHD and HCM differ in the structural alterations in the arteriolar bed. Medial hypertrophy and periarteriolar fibrosis prevail in HHD, and reduced arteriolar density is found in HCM. Different microvascular remodelling at the level of arterioles indicates distinct pathophysiologic processes that may contribute to the clinically observed disturbance of coronary microperfusion in these two diseases.

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.

Objectives of High Blood Pressure Treatment: Left Ventricular Hypertrophy, Diastolic Function, and Coronary Reserve

The prehypertrophic state of hypertensive heart disease is characterized by morphologic changes (interstitial fibrosis, increase in intramyocardial arteriolar wall thickness) as well as by functional alterations (diastolic dysfunction, decrease in coronary reserve). These changes most probably represent the earliest cardiac end-organ lesions that can clinically be detected. In cardiac hypertrophy, long-term (9-12 months) pharmacotherapy with beta-blockers, calcium channel blockers, or ACE inhibitors reverses left ventricular hypertrophy by 8% to 14%, whereas marked improvement in coronary reserve and diastolic dysfunction is achieved by calcium blocker and preferably by ACE inhibitors.

Update 2001¶Myokarditis – Kardiomyopathie

ZusammenfassungDie Entzündung des Myokards ist eine häufige kardiale Erkrankung.Neue molekularbiologische und immunhistologische Methoden können helfen, die Myokarditis in Hinblick auf eine chronische Viruspersistenz und die Aktivität einer myokardialen Entzündung zu sichern. Der Zusammenhang zwischen viraler Myokarditis und Entwicklung einer dilatativen Kardiomyopathie ist von besonderer Bedeutung. Hieraus ergeben sich neue Möglichkeiten zur Prognoseabschätzung und Planung einer spezifischen immunsuppressiven, immunmodulatorischen und antiviralen Therapie.AbstractMyocarditis is a common cardiological disease.New molecular biological and immunohistological methods have confirmed the persistence of viral infection and chronic myocardial inflammation in a considerable number of patients. A causal link between viral myocarditis and the development of dilated cardiomyopathy has been recognized. This has prognostic implications and helps for the decision of a specific immunosuppressive, immunomodulatory and antiviral therapy.

Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP–1) and its inhibitor (TIMP–1) in DCM patients

SummaryLeft ventricular dilation and myocardial remodeling are hallmarks of dilated cardiomyopathy (DCM). It is assumed that left ventricular dilation is caused by the disintegration of the collagenous network by increased collagenolytic activity of matrix metalloproteinases (MMPs) and their adequate tissue inhibitors (TIMPs).In this study the myocardial MMP–1 and TIMP–1 mRNA expressions were investigated by using real–time quantitative PCR analysis from right septal endomyocardial biopsies of patients with dilated cardiomyopathy (n = 46) and control subjects (n = 11). The volume density (Vv%) of collagen was measured morphometrically. Classification was done according to LV diameters [left ventricular enddiastolic diameter (LVEDD, cm) calculated to body surface area (BSA, m2)] into three DCM groups: group I (LVEDD–BSA > 2.7–3.0 cm/m2), group II ( > 3.0–3.6 cm/m2), group III ( > 3.6 cm/m2), controls (< 2.7 cm/m2).Compared with controls, the MMP–1 expression in patients with DCM was significantly increased (119.2 ± 45.2 vs. 1.3 ± 0.4; p < 0.001) as was TIMP–1 expression (9.6 ± 1.2 vs. 1.3 ± 0.4; p < 0.01). Moreover the MMP–1 and TIMP–1 expression varied according to LV diameter: group I (MMP–1: 8.7 ± 3.5; p = 0.33; TIMP– 1: 4.5 ± 1.2; p < 0.01); group II (MMP–1: 211.4 ± 86.0; p < 0.001; TIMP–1: 12.5 ± 1.9 ; p < 0.001); group III (MMP–1: 38.8 ± 22.6; p < 0.01; TIMP–1: 8.1 ± 1.7; p < 0.001). Compared with controls, the collagen level in DCMPt. was significantly increased: 5.0 ± 0.6 vol% vs 1.2 ± 0.2 vol% p < 0.001 and correlates with LV diameter. This study reveals that the overexpression of MMP–1, which is associated with an increased ratio of MMP–1/TIMP–1 in DCM, indicates an activated collagenolytic system while replacement fibrosis is accumulating. The MMP–1 overexpression is mainly found in moderately dilated DCM hearts (group II) indicating the dynamic process of LV dilation and the importance of collagenases in the early phase of LV remodeling.

What is the Value of Home (Self) Blood Pressure Monitoring in Patients with Hypertensive Heart Disease

The acceptable maximal blood pressure values for patients monitoring their own blood pressure at home have not yet been determined. Risk of cardiovascular disease may be increased at lower blood pressure limits than those suggested by the World Health Organization (WHO) for clinic readings. We have investigated 25 patients with proven hypertensive small-vessel disease and compared self-monitored, ambulatory 24-h (ABPM) and clinic blood pressure measurements. The diagnosis of hypertensive small-vessel disease was based on clinical evidence of myocardial ischemia, angiographic exclusion of coronary heart disease, and abnormal single-photon emission computed tomography (SPECT) thallium-201 myocardial scintigraphy. Mean self-monitored values were 143.4 +/- 13.6/84.0 +/- 9.4 mm Hg (95% confidence intervals 137.6-149.0 mm Hg for systolic and 80.1-87.9 mm Hg for diastolic blood pressure). Both home and ambulatory daytime readings (141.2 +/- 11.8/83.9 +/- 10.2 mm Hg) were significantly lower than the clinic readings by the physicians (clinic systolic, 169.2 +/- 16.5 mg; clinic diastolic, 95.0 +/- 11.6 mm Hg; P < .0001 v home and ambulatory readings). There was no significant difference between home and ambulatory readings. Agreement between home and ambulatory values was much closer than for clinic v ABPM readings. The respective correlation coefficients for systolic values were r = 0.702 (home v ABPM; P < .0001) and r = 0.32 (clinic v ABPM; NS). For diastolic values correlation coefficients were r = 0.674 (home v ABPM; P < .0002) and r = 0.574 (clinic v ABPM; P < .003) respectively. In conclusion, the reported results suggest that the WHO suggested definition of hypertension (> or = 140/90 mm Hg) may be set too high when blood pressures are measured by the patient at home. A cutoff value of < 135/85 mm Hg, as in ABPM, may be a more realistic upper limit for self-monitoring.