Joachim Manthey

The effect of aortic valve replacement on survival.

We retrospectively studied 252 operated and 47 unoperated patients with isolated aortic valve disease. Aortic valve replacement (AVR) was recommended to all patients based on clinical and hemodynamic data. Preoperative hemodynamic and angiographic data were similar in operated and unoperated cohorts. Seventy-one percent of patients received a Bjork-Shiley prosthesis. Operative mortality was 7% for the entire surgical series. For patients with predominant aortic stenosis (AS), survival at 3 years was 87% in operated and 21% in unoperated patients (p < 0.001). For patients with predominant aortic insufficiency (Al), the 5-year survival rate was 86% in operated and 87% in unoperated patients (NS). AVR improved long-term survival inpatients with AS who had normal or impaired left ventricular (LV) function.In patients with Al and normal LV function, survival was not improved after AVR, but those with LV dysfunction who were operated on tended to survive longer (NS). Long-term survival of unoperated patients with AI was better than that in unoperated patients with AS. We conclude that AVR improves long-term survival in patients with AS who have normal or abnormal LV function, and that AVR does not change long-term survival in patients with Al, although those with LV dysfunction tended to survive longer.

Reduction of coronary reserve: a mechanism for angina pectoris in patients with arterial hypertension and normal coronary arteries.

The pathogenesis of angina pectoris in patients with left ventricular hypertrophy secondary to arterial hypertension and with normal coronary arteries remains uncertain. We measured coronary blood flow (argon method) in 12 control subjects and in 16 patients with arterial hypertension at rest and after intravenous administration of dipyridamole (0.5 mg/kg). In the patients with arterial hypertension, coronary blood flow response to dipyridamole was markedly reduced (p less than .001 as compared with control values). During coronary vasodilation there was a linear correlation between coronary resistance and left ventricular end-diastolic pressure (r = .67, p less than .001). Left ventricular catheter biopsy specimens did not reveal alterations in myocardial microvasculature. These findings suggest that reduction of coronary reserve may be an important contributor to the pathogenesis of angina pectoris in these patients.

Determinants of survival in patients with congestive cardiomyopathy: quantitative morphologic findings and left ventricular hemodynamics.

We analyzed data from 68 consecutive patients with congestive cardiomyopathy to evaluate the prognostic significance of quantitative morphologic findings in left ventricular myocardium as compared with the prognostic significance of left ventricular hemodynamics. Left ventricular endomyocardial biopsy specimens were obtained from all patients during diagnostic heart catheterization. Myocardial fiber diameter, volume fraction of interstitial fibrosis, and intracellular volume fraction of myofibrils were determined by light-microscopic morphometry. All patients had normal coronary arteriograms, but reduced left ventricular ejection fractions. There were 23 deaths during a mean follow-up period of 1124 days. Multivariate regression analysis (Cox model) revealed that left ventricular ejection fraction (p less than .00001) and left ventricular systolic pressure (p less than .01), but not morphometric findings in biopsy specimens, were independent predictors of cardiac death. Thus, morphologic findings in the left ventricular myocardium do not contribute significantly to the prognostic evaluation in patients with congestive cardiomyopathy studied by hemodynamic and angiographic methods.

Intracoronary thrombolysis in acute myocardial infarction: Duration of ischemia as a major determinant of late results after recanalization

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15), and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction, and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured. Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area, and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59%) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p less than 0.05; regional ejection fraction: 26%, p less than 0.05) and group B (ejection fraction: 44%, p less than 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p less than 0.05) and group B (2,106 U/liter, p less than 0.05). Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.

Quantitative morphologic findings of the myocardium in idiopathic dilated cardiomyopathy

This study assesses the relation between quantitative morphologic findings and left ventricular contractile function in patients with idiopathic dilated cardiomyopathy. Left ventricular endomyocardial catheter biopsy specimens were obtained from 73 patients during diagnostic heart catheterization. All patients had normal coronary arteriograms but abnormal electrocardiograms. Twenty-six patients had normal left ventricular function (ejection fraction greater than or equal to 55%), whereas 47 patients had contractile dysfunction (ejection fraction less than or equal to 54%). Myocardial fiber diameter, volume fraction of interstitial fibrosis, and intracellular volume fraction of myofibrils were determined by light microscopic morphometry. Results of light microscopic morphometry were confirmed by electron microscopic morphometry in 12 patients. The coefficient of variation (analysis of several biopsies from the same patient) was 6% for determination of fiber diameter, 43% for interstitial fibrosis, and 3% for volume fraction of myofibrils. Fiber diameter (r = -0.32, p less than 0.01) and fibrosis (r = -0.47, p less than 0.001) showed a negative correlation, the volume fraction of myofibrils (r = 0.55, p less than 0.001) and calculated myofibrillar mass per 100 g of myocardium (r = 0.64, p less than 0.001) a positive correlation with the ejection fraction. Thus, (1) sampling error is low for determination of fiber diameter and myofibrils but high for evaluation of fibrosis, and (2) a reduction in the volume fraction of myofibrils and an increase in fibrosis are morphologic correlates of left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy.

Coronary dilatory capacity in idiopathic dilated cardiomyopathy: analysis of 16 patients.

Hemodynamic function and overall coronary blood flow (argon technique) were measured in 16 patients with idiopathic dilated cardiomyopathy (IDC) and in 12 patients without detectable heart disease (control subjects) referred for precordial pain. In patients with IDC, coronary blood flow was normal at rest (78 +/- 17 ml/100 g-min versus 78 +/- 9 in control subjects). During maximal inducible coronary vasodilation (dipyridamole, 0.5 mg/kg), coronary blood flow was significantly reduced (142 +/- 38 ml/100 g.min versus 301 +/- 64 in control subjects; p less than 0.001). Consequently, obtainable minimal coronary resistance was increased in IDC (0.54 +/- 0.20 mm Hg/ml/100 g.min versus 0.23 +/- 0.04 in control subjects; p less than 0.001). In patients with IDC, left ventricular (LV) end-diastolic pressure was significantly increased (19 +/- 11 mm Hg versus 6 +/- 3 in control subjects; p less than 0.005), and the LV ejection fraction was diminished (36 +/- 11% versus 72 +/- 3% in control subjects; p less than 0.001). In patients with IDC, LV end-diastolic pressure correlated significantly with the obtained minimal coronary resistance after application of dipyridamole (r = 0.85; p less than 0.001). LV catheter biopsy specimens revealed no alterations in myocardial microvasculature. Thus, coronary dilatory capacity is impaired in patients with IDC, due partially to an increase in extravascular component of coronary resistance.

Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy.

Twenty-one patients with acute myocardial infarction, admitted to the hospital within 4 hours after the onset of symptoms, were studied by seven-pinhole thallium-201 scintigraphy before and I hour and 24 hours after intracoronary fibrinolysis using streptokinase. The size of the thallium-201 perfusion defect was assessed from myocardial cross sections reconstructed from the original seven-pinhole data and expressed as a fraction of left ventricular circumference.Recanalization was achieved in 16 patients within 3.9 ± 1.6 hours after onset of symptoms (group A). In these patients, the size of the perfusion defect had decreased from 36 ± 17% to 19 ± 15% (p < 0.001) at 24 hours. No significant change was detected by redistribution at 1 hour after the intervention. In five patients, intracoronary fibrinolysis was unsuccessful, and the vessel remained occluded (group B). The thallium-201 perfusion defect affected 40 ± 15% of the left ventricular circumference before the intervention; it remained virtually unchanged at 1 hour (37 ± 16%) and at 24 hours (41 ± 15%) after fibrinolysis. The perfusion defect was most reduced in patients with extensive collaterals supplying the ischemic area or with subtotal occlusion of the affected coronary artery.We conclude that successful intracoronary fibrinolysis may reduce the size of the thallium-201 perfusion defect in many patients with acute myocardial infarction. One important factor in the final result may be the presence of residual coronary flow supplied by extensive collaterals or by subtotal occlusion of the affected coronary artery when reperfusion is achieved around 4 hours after the onset of symptoms.

ACE inhibition improves vagal reactivity in patients with heart failure

The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement.

Sustained improvement of pulmonary hemodynamics in patients at rest and during exercise after thrombolytic treatment of massive pulmonary embolism.

This study assessed the long-term effects of thrombolytic treatment in patients with acute massive pulmonary embolism (PE). Seven patients with PE that followed deep-vein thrombosis underwent pulmonary angiography and pressure measurements before and 6 +/- 3 days (mean +/- SD) and 15 +/- 4 months after treatment with intrapulmonary infusions of urokinase (average dose 1724 U/kg X hr) and heparin (average dose 17 U/kg X hr). Treatment was guided by daily measurements of pulmonary arterial (PA) pressure and was continued until PA pressure had normalized (average of 6 days). Late after treatment patients returned for pulmonary angiographic examination, right heart catheterization at rest and during bicycle exercise, and phlebography of the deep veins of both legs. Pulmonary angiograms showed massive obstruction before therapy (Walsh index 15 +/- 2 points of a maximum of 18 points), which was improved 6 days (3 +/- 3 points) and 15 months (1 +/- 2 points) after therapy. Mean PA pressure declined from 37 +/- 9 to 13 +/- 3 mm Hg after 6 days and to 15 +/- 3 mm Hg after 15 months. No recurrence of PE was observed. In six of seven patients at rest and during bicycle exercise (up to 100 W) in the supine position mean PA pressure and total pulmonary resistance remained within normal limits. Over the short term all patients showed clinical signs of deep-vein thrombosis; 15 months later four patients had normal deep veins, but three patients had still phlebographic signs of old thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronary thrombolysis in acute myocardial infarction: an attempt to quantitate its effect by comparison of enzymatic estimate of myocardial necrosis with left ventricular ejection fraction.

The quantity of myocardium was estimated that can be salvaged by reperfusion of acute transmural myocardial infarction (MI). Serial analysis of serum creatine kinase (CK) activity was carried out in 41 consecutive patients with acute MI who underwent intracoronary thrombolysis. Enzymatic estimate of MI size was calculated using an average (method A) and an individually determined elimination constant (method B). Left ventricular ejection fraction 4 weeks after successful thrombolysis (cineangiogram) correlated inversely with MI size (method A: r = -0.85, method B: r = -0.76; both p less than 0.001). Patients with recanalization within 4 hours after the onset of symptoms were assembled in group A1 (n = 13, early reperfusion), and patients with successful recanalization after 4 hours in group A2 (n = 16, late reperfusion). Group B consisted of 12 patients without reperfusion. MI size in group A1 was 21 CK-g-Eq (method A) and 23 CK-g-Eq (method B), in group A2 50 CK-g-Eq (method A) and 54 CK-g-Eq (method B), and in group B 73 CK-g-Eq (method A) and 63 CK-g-Eq (method B). Mean values in group A1 were lower than in group A2 and group B (p less than 0.05). It is concluded that MI size was significantly reduced to about one third after early reperfusion as compared with no reperfusion. In contrast, MI size was not significantly reduced after late reperfusion.