Andreas Hartmann

Serial evaluation of left ventricular function by radionuclide ventriculography at rest and during exercise after orthotopic heart transplantation

Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients <6 months, 7–12 months, 13–24 months and >24 months after transplantation. Ejection fraction decreased significantly from <6 months to 13–24 months after transplantation (rest: 69.1%±9.7% to 56.7%±8.3%, P<0.05; exercise: 70.4%±11.3% to 59%±8%, P<0.05). Heart rate increased significantly during exercise after >2 years (90.2±10.5 beats/min to 103.5±15 beats/min, P<0.05) but not within 6 months after transplantation (98.5±12.8 beats/min to 99.07±15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2±0.96 edv/s <6 months after transplantation to 3.3±0.66 edv/s (P<0.05) 13–24 months and 3.3±0.64 edv/s (P<0.05)>24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation.

Endothelium-dependent and endothelium-independent flow regulation in coronary vascular regions supplied by arterial and venous bypass grafts

The endothelium-dependent and endothelium-independent vasodilation of arterial and venous coronary bypass grafts and of epicardial conduit vessels and microcirculatory coronary vessels supplied by these grafts was investigated. Vasodilatory response and flow regulation were tested with cumulative intracoronary doses of acetylcholme (25 and 50 µg i.e.), nitroglycerin (0.3 mg i.e.), and papaverine (10 mg i.e.) in 10 patients (age 60 ± 2.3 years) with arterial grafts and in 16 patients (age 57.7 ± 1.5 years) with venous grafts. The effect of acetylcholme on arterial and venous bypass grafts and on large conduit arteries was evaluated by quantitative coronary angiography. Coronary blood flow velocity changes as a parameter of microcirculatory function were measured by intraluminal Doppler ultrasound. Indices for coronary flow and coronary resistance were calculated from the mean Doppler flow velocity and the computed cross-sectional vascular area. The coronary resistance decreased endothelium dependent after 25 and 50 µg of acetylcholme by 16 ± 30% (p

Somatic pain threshold and reactive hyperemia in autonomic diabetic neuropathy and silent myocardial ischemia

In 31 patients with coronary artery disease (autonomic neuropathy, n = 11; diabetes without neuropathy, n = 10; silent myocardial ischemia without diabetes, n = 10) difference in somatic pain threshold and plethysmographically determined reactive hyperemia induced by forearm skeletal muscle ischemia was investigated. There was no difference in reactive hyperemia after passive maximum forearm ischemia in the three groups indicating identical vascular reactivity. After symptom-limited ischemic work however, reactive hyperemia was significantly higher in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) as in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy (9/10). In conclusion, patients with silent myocardial ischemia have a higher ischemic tolerance in the working forearm as compared to diabetic patients with and without neuropathy. There is a quantitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.

Nitrate Therapy in Heart Failure

Nitrates are drugs of first choice in patients with acute heart failure. Acute pulmonary edema can be successfully treated with single or repeated doses of sublingual nitroglycerin. In cases of prolonged acute heart failure, e.g. in the setting of acute myocardial infarction, nitroglycerin or isosorbide dinitrate can be given by the intravenous route for up to 24 h. Patients with acute myocardial infarction usually benefit from nitrate therapy if filling pressures are high and/or left ventricular function is compromised. Nitrate therapy can be considered safe if arterial blood pressure is maintained above 95 mm Hg. With these precautions nitrates can reduce infarct size and the incidence of complications as well as improve long-term prognosis. In the chronic treatment concern has risen with regard to possible nitrate tolerance. Thus, therapy schedules allowing for nitrate-poor phases are generally recommended. Therapy schedules with constant-rate delivery of drugs achieved with patches or intravenous administration of nitrates should be used with caution.

Is technetium-99 m-pyrophosphate scintigraphy valuable in the diagnosis of cardiac amyloidosis?

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloid fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.

Endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the internal mammary artery before and after bypass grafting

OBJECTIVE It was the goal of this study to compare endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the left internal mammary artery before and after bypass graft surgery. METHODS The native internal mammary artery in situ was investigated in 13 patients (age 61.8 +/- 8.0 years) with angiographically proven coronary artery disease. The internal mammary artery after bypass grafting was investigated in ten patients (age 60.8 +/- 7.3 years) 3.5 +/- 2.8 years after the operation. Flow reserve was evaluated endothelium-dependent with acetylcholine (ACh 25 and 50 microg i.c.) and endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler blood flow velocity measurements and the vascular cross-sectional area as determined by quantitative angiography. An index for vascular resistance was defined as the ratio of pressure gradient and resting or peak flow. RESULTS After endothelium-dependent stimulation with acetylcholine 25 microg (50 microg), flow in the internal mammary increased by 352.3 +/- 152% (412 +/- 145%) before surgery, whereas it increased only by 213 +/- 134% (193 +/- 120%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a flow increase of 391 +/- 234% before surgery vs. 315 +/- 135% after surgery (n.s.). The resistance index decreased after endothelium-dependent stimulation with acetylcholine 25 microg(50 microg) to 35 +/- 16.8% (28 +/- 8.9%) before surgery, whereas it decreased only to 59 +/- 26% (72 +/- 43%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a decrease of the vascular resistance index to 31 +/- 14% before surgery vs. 32 +/- 14% after surgery (n.s.). CONCLUSION Vascular regions supplied by the internal mammary artery as a graft demonstrate a significantly reduced endothelium-dependent flow reserve but a preserved endothelium-independent flow reserve as compared to vascular regions supplied by the native internal mammary artery. The selective decrease in endothelium-dependent flow reserve may be due to microvascular changes in the myocardial region supplied by the internal mammary artery after bypass grafting.

Extracellular matrix structure after heart transplantation

Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 microm2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2 (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter 31.4 microm). It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.

Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy

In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac microvascular vasomotor response as a prognostic marker of left ventricular function in cardiac transplant recipients

T HE long-term survival of patients after heart transplantation is limited by the development of cardiac allograft vasculopathy (CAV).’ The lumina of the smaller intramyocardial branches are often occluded before those of the larger epicardial arteries and this results in small, multiple, stellate infarcts.’ To assess the degree to which transplant vascular sclerosis affects the resistance vessels, coronary blood flow measurement is useful. Several studies in transplant recipients suggest that resistance vessel function is altered at an early stage of the coronary disease process. 3,4 The left ventricular systolic function is relatively well preserved in patients without significant acute rejection5 but the importance of microvascular vasomotor (dys)function in the development of reduced left ventricular function has not been investigated. Therefore, it was the purpose of the present study to assess the relationship of coronary blood flow reserve (CFR) and subsequent changes in left ventricular systolic function to establish the clinical utility of coronary flow measurement to identify a distinct subset of patients in whom closer monitoring and aggressive risk factor modification may be indicated.