Volker Wiegand

Molecular approaches to enteroviral diagnosis in idiopathic cardiomyopathy and myocarditis

Enteroviruses are thought to be etiologic agents in some cases of human myocarditis and dilated cardiomyopathy. Murine models of acute coxsackievirus B3 myocarditis implicate coxsackie B viruses as possible causes of human myocarditis. Indirect evidence implicating enteroviruses as causative agents in human heart disease derives from serologic studies. More recently, direct evidence for enteroviral presence in diseased human heart tissues has been obtained by nucleic acid hybridization analyses. Although the data suggest that enteroviral infections may be associated with 18% to 50% of cases of myocarditis or dilated cardiomyopathy, or both, causality has not been established. Unanswered questions remain regarding the specific identity of the enteroviral genomes detected in the human heart and the potential for enteroviruses to persist in the heart.

Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery

Intracoronary stenting has been introduced as an adjunct to balloon angioplasty aimed at overcoming its limitations, namely acute vessel closure and late restenosis. This study reports the first experience with the Wiktor stent implanted in the first 50 consecutive patients. All patients had restenosis of a native coronary artery lesion after prior balloon angioplasty. The target coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in 7 patients and the right coronary artery in 17 patients. The implantation success rate was 98% (49 of 50 patients). There were no procedural deaths. Acute or subacute thrombotic stent occlusion occurred in 5 patients (10%). All 5 patients sustained a nonfatal acute myocardial infarction. Four of these patients underwent recanalization by means of balloon angioplasty; the remaining patient was referred for bypass surgery. A major bleeding complication occurred in 11 patients (22%): groin bleeding necessitating blood transfusion in 6, gastrointestinal bleeding in 3 and hematuria in 2. Repeat angiography was performed at a mean of 5.6 +/- 1.1 months in all but 1 patient undergoing implantation. Restenosis, defined by a reduction of greater than or equal to 0.72 mm in the minimal luminal diameter or a change in diameter stenosis from less than to greater than or equal to 50%, occurred in 20 (45%) and 13 (29%) patients, respectively. In this first experience, the easiness and high technical success rate of Wiktor stent implantation are overshadowed by a high incidence of subacute stent occlusion and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.

BackgroundIntracoronary stents have been suggested as a method of reducing the restenosis rate after balloon angioplasty. Proliferation of vascular smooth muscle cells is a major contributing factor to the restenosis process. Heparin and some of its derivatives have been shown to inhibit smooth muscle cell proliferation. We investigated the effect of low-molecular-weight heparin on the proliferative response after implantation of a balloon-expandable tantalum stent in previously deendothelialized coronary artery segments of hypercholesterolemic minipigs. Methods and ResultsMinipigs were fed a diet containing 2% cholesterol, starting 1 month before balloon denudation of the endothelium in a coronary artery. One month later, a stent was implanted at this site. Animals were killed after 4 weeks (group 1, n = 6) or 3 months (group 2, n = 6). Animals in group 3 (n = 6), also followed for 4 weeks after stenting, received subcutaneous low-molecular-weight heparin at a dose of 200–300 units/kg anti-factor Xa activity per day in addition to the chronic acetylsalicylic acid (100 mg/day) also administered to groups 1 and 2. Eighteen of 22 animals survived to the end of the study. Angiography revealed patent stents in all surviving animals. In group 1, histological analysis showed extensive neointimal proliferation around stent struts. Maximal neointimal thickness seen in group 1 averaged 0.93±0.11 mm, was lower after 3 months (0.8±0.14 mm) in group 2, but was significantly reduced (0.44±0.18 mm, p < 0.01) in group 3. ConclusionsThese data show a significant reduction of the neointimal proliferative response to coronary stent implantation by low-molecular-weight heparin.

Intravascular ultrasound imaging of human coronary arteries after percutaneous transluminal angioplasty: Morphologic and quantitative assessment

An intravascular ultrasound catheter system was used in patients to assess the effect of percutaneous transluminal coronary angioplasty. In 14 out of 16 patients, the intravascular ultrasound catheter could be successfully advanced to the site of a previous dilatation. Qualitative assessment of the cross-sectional images revealed intimal thickening and an increase of ultrasound reflectance and calcification at atherosclerotic coronary arteries. A disruption of the obstructing plaque and evidence for local dissections (11 of 14 cases) were observed after angioplasty. The quantitative comparison between angiography and the ultrasound measurement showed a close correlation for vessel sites distant to the dilatation (r = 0.91 for vessel diameter; r = 0.86 for luminal area; p less than 0.001). After angioplasty, the quantitative evaluation of the dilated area was possible in 11 cases. The correlation of angiographic and sonographic measurements of these segments was good for the assessment of the vessel diameter (r = 0.82, p less than 0.001), but poor for the determination of the luminal area (r = 0.48, p = 0.10). This difference reflected the complex morphology of the vessel lumen after angioplasty, which would be better assessed by the cross-sectional sonographic technique than by contrast angiography. The intravascular imaging of coronary arteries provides a new and unique method to obtain information on the plaque morphology and composition, and to assess the local effects of interventional procedures and their complications.

Angiographic predictors of recurrence of restenosis after Wiktor stent implantation in native coronary arteries

Intracoronary stenting has been proposed as an adjunct to balloon angioplasty to improve the immediate and long-term results. However, late luminal narrowing has been reported following the implantation of a variety of stents. One of the studies conducted with the Wiktor stent is a prospective registry designed to evaluate the feasibility, safety and efficacy of elective stent implantation in patients with documented restenosis of a native coronary artery. To identify angiographic variables predicting recurrence of restenosis, the angiograms of the first 91 patients with successful stent implantation and without clinical evidence of (sub)acute thrombotic stent occlusion were analyzed with the Computer Assisted Angiographic Analysis System using automated edge detection. The incidence of restenosis was 44% by patient and 45% by stent according to the 0.72 mm criterion, and 30% by patient and 29% by stent according to the 50% diameter stenosis criterion. The risk for restenosis for several angiographic variables was determined using an univariate analysis and is expressed as odds ratio with corresponding confidence interval. The only statistically significant predictor of restenosis was the relative gain when it exceeded 0.48 using the 0.72 mm criterion (odds ratio 2.7, 95% confidence interval 1.1-6.4). Furthermore, the relation between the relative gain (increase in minimal luminal diameter normalized to vessel size) as angiographic index of vessel wall injury and relative loss (decrease in minimal luminal diameter normalized to vessel size) as index of neointimal thickening was analyzed using a linear regression analysis. When using the categorical approach to address restenosis, there is an increased risk for recurrent restenosis when the relative gain exceeds 0.48. The continuous approach underscores this concept by indicating a weak but positive relation between the relative gain and relative loss.

Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

OBJECTIVES The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. BACKGROUND Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. METHODS In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). RESULTS Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. CONCLUSIONS Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.

Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy☆☆☆

There is increasing evidence that chronic enhanced exogenous or endogenous catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamic status and prognosis. The cause of this deterioration may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study, the calcium channel antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60 to 90 mg three times daily) in addition to conventional therapy of digitalis, diuretics and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in this control group received adjunctive diltiazem treatment after initially receiving conventional therapy alone. The three patient groups were similar in all hemodynamic and anamnestic features. Only patients with reduced myofibrillar volume fraction on myocardial biopsy were included in the trial, because they could be expected to show hemodynamic deterioration. The mean survival time was 29 months in the control group, whereas no patient in the diltiazem group died over a mean follow-up period of 15.4 months (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and New York Heart Association functional class improved significantly in the diltiazem group and during the diltiazem period in the crossover patients, but deteriorated in the control group. The results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on mortality, hemodynamics and symptoms.

Restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions

In an open clinical study, a xenon-chloride excimer laser was used for angioplasty of coronary stenoses (n = 48) and chronic total occlusions (n = 56) in 104 patients. Multifiber catheters (4.0F to 5.5F) transmitted 37 to 120 mjoules/mm2 of fiber surface. Excimer laser angioplasty was successful in 43 patients with a stenosis (89%), followed by percutaneous transluminal coronary angioplasty in 21 patients (49%) to reduce the stenosis to less than 50% luminal narrowing. In 39 patients (70%) with a chronic occlusion (age 1 to 14 months), recanalization by means of excimer laser angioplasty was successful, with subsequent percutaneous transluminal coronary angioplasty performed in 23 patients. Major complications included one perforation, one acute occlusion, and two severe dissections. Six-month angiographic follow-up examinations after successful angioplasty were completed in 40 patients (98%) with stenoses and 34 (94%) with occlusions. Restenosis (greater than 20% decrease in luminal diameter) occurred in 13 patients (33%) with stenoses and in 16 patients (47%) after angioplasty of a chronic occlusion. These long-term results indicate that restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions is similar to reported results of conventional balloon angioplasty.

Effect of intracoronary superoxide dismutase on regional function in stunned myocardium.

This study investigates the ischemic-time dependency of dysfunction in reversibly ischemic myocardium and the effect of postischemic oxygen free radical scavenging thereupon. In open chest pigs, occlusion of the distal left anterior descending coronary artery (LAD) for 4 (n = 5), 8 (n = 5), or 12 min (n = 5) resulted in paradoxical systolic and diastolic regional function, measured by ultrasonic crystals. With onset of reperfusion, systolic shortening (SS) and diastolic lengthening (DL) normalized completely in the 4− and 8-min groups, followed by a significant decrease to 50% control in the 8-min group. In the I2-min group, recovery of SS and DL was only partial. In two further groups, animals received an intracoronary infusion of either recombinant human superoxide dismutase (SOD, n = 6) or placebo (n = 6), starting with reperfusion after an 8-min LAD occlusion. SOD improved recovery of SS compared with placebo (p < 0.05), but DL and the depression of SS during later reperfusion were not influenced. Mitochondrial function after 90 min of reperfusion was not impaired in ischemicreperfused compared to control myocardium. We conclude that the degree of postischemic dysfunction increases with the duration of ischemia. Oxygen free radical scavenging by SOD, starting not before reperfusion, fails to prevent myocardial stunning. Mitochondrial function is intact in such myocardium.

Doppler echocardiographic analysis of cardiac flow during the Mueller manoeuver

Abstract. The inspiration against a closed airway, the Mueller manoeuver, leads to a negative intrathoracic pressure. It is controversially discussed whether this is causing an augmentation of right heart murmurs. There is only limited knowledge on the temporal relationship of the negative intrathoracic pressure with right and left ventricular filling and stroke volume. To investigate this relationship, the flow through the mitral, aortic, tricuspid and pulmonary valves was studied continuously by Doppler echocardiography during a standardized Mueller manoeuver in 15 healthy subjects (age 45 ± 10 years). Five heart beats after the initiation of the manoeuver, flow through the mitral and aortic valve decreased 12.2 ± 7.2% (P < 0.001) and 10.1 ± 6.6% (P < 0.001), respectively. A transient increase of 15.1 ± 9.2% (P < 0.001) in tricuspid flow was followed by a 14.3 ± 9.8% (P < 0.005) increase of flow through the pulmonary artery. Ten heart beats after the initiation of the Mueller manoeuver, flow through the pulmonary artery again reached baseline, while tricuspid flow remained below baseline values. In contrast to previous studies, our results indicate that the Mueller manoeuver causes a small and transient increase in right ventricular stroke volume which is unlikely to cause a marked augmentation in right heart murmurs.