Gunhild Herrmann

Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease

Background— Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. Methods and Results— We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33±3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. Conclusions— Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Laser angioplasty of restenosed coronary stents: Results of a multicenter surveillance trial

OBJECTIVES This study evaluated safety and efficacy of excimer laser angioplasty for treatment of restenosed or occluded coronary stents. BACKGROUND Balloon angioplasty of in-stent restenosis is limited by a high recurrence rate. Debulking by laser angioplasty is a novel concept to treat in-stent restenosis. METHODS A total of 440 patients with restenoses or occlusions in 527 stents were enrolled for treatment with concentric or eccentric laser catheters and adjunctive balloon angioplasty. RESULTS Laser angioplasty success (< or =50% diameter stenosis after laser treatment or successful passage with a 2.0-mm or 1.7-mm eccentric laser catheter) was achieved in 92% of patients. Adjunctive balloon angioplasty was performed in 99%. Procedural success (laser angioplasty success followed by < or =30% stenosis with or without balloon angioplasty) was 91%. There was neither a significant difference in success with respect to lesion length, nor were there differences between small and large vessels or native vessels and vein grafts. Success was higher and residual stenosis lower using large or eccentric catheters. Serious adverse events included death (1.6%, not directly laser catheter related), Q-wave myocardial infarction (0.5%), non-Q-wave infarction (2.7%), cardiac tamponade (0.5%) and stent damage (0.5%). Perforations after laser treatment occurred in 0.9% of patients and after balloon angioplasty in 0.2%. Dissections were visible in 4.8% of patients after laser treatment and in 9.3% after balloon angioplasty. Reinterventions during hospitalization were necessary in 0.9% of patients; bypass surgery was performed in 0.2%. CONCLUSIONS Excimer laser angioplasty with adjunctive balloon angioplasty is a safe and efficient technology to treat in-stent restenoses. These data justify a randomized comparison with balloon angioplasty.

COAGULATION ACTIVATION IN PATIENTS UNDERGOING DIRECTIONAL CORONARY ATHERECTOMY

Restenosis is a major problem of percutaneous transluminal coronary angioplasty (PTCA) and related procedures. To better understand the underlying pathophysiologic mechanisms, coagulation and fibrinolytic variables were analysed prospectively in 35 patients after directional coronary atherectomy (DCA) and in 20 control patients undergoing diagnostic heart catheterisation and coronary angiography. Blood samples were taken before and 1 h, 24 h and 48 h after the procedure. No subacute thrombosis or unstable angina were documented in any patient. In 8 out of these 35 patients late restenosis was diagnosed during follow-up angiography 3-6 months after DCA. In these 8 patients prothrombin fragments (F1 + 2) rose from 0.7 to 0.9 nmol/l (P < 0.01) and thrombin-antithrombin III complexes (TAT) from 2.9 to 6.0 micrograms/l (P < 0.01), but not significantly in 27 patients without restenosis and in the control patients. In patients with late restenosis plasminogen activator inhibitor (PAI-1) also increased from 2.4 to 4.9 U/ml (P < 0.05) 24 h after DCA while there were no significant changes in patients without restenosis and in control patients. D-Dimer/TAT ratio reflecting the balance between clotting activation and fibrinolysis was significantly lower after 24 h in restenosis patients. The findings suggest that coagulation activation and hypofibrinolysis during 48 h after DCA might be associated with the development of late restenosis.

Relationship between therapeutic time intervals and intermediate term left ventricular systolic function in patients treated with facilitated percutaneous coronary intervention for acute myocardial infarction

SummaryBackgroundThe concept of initiating fibrinolytic therapy in patients who cannot undergo immediate percutaneous coronary intervention (PCI) in the setting of acute ST-segmentelevation myocardial infarction (STEMI) has been proposed as a strategy to improve outcomes. However, evidence supporting the use of this strategy is not conclusive, and the results of recent randomized controlled trials are apparently contradictory. Probably, the time points of administration of the adjunctive thrombolytics and antiplatelet agents and the time loss until coronary intervention have a major influence on the discrepancy of outcomes in different trials. Therefore, the relationship between therapeutic time intervals and outcome in patients treated with facilitated PCI has been analyzed.MethodsIn this single center retrospective study, 131 patients with STEMI were treated with a combined pharmaco-mechanical reperfusion strategy using half-dose r-tPA combined with a glycoprotein (GP) IIb/IIIa antagonist prior to PCI. Specific time points were recorded for each patient, including the time of symptom onset, the time of first medical contact, the start of intravenous thrombolysis, the time of administration of the GP IIb/IIIa antagonist and the start of coronary intervention. We then examined the relationship between the time delay from symptom onset to the initiation of various steps of treatment and the residual myocardial damage as expressed by the severity of both global and regional myocardial dysfunction calculated from a left ventriculography study performed 3 months later.ResultsThe median time from symptom onset to the first medical contact, with 25th and 75th percentiles in parentheses, was 1.25 h (0.75, 3), from symptom onset to initiation of thrombolytic therapy 2.25 h (1.25, 3), to initiation of GP IIb/ IIIa inhibitor therapy 3.5 h (2, 5.69), and to the start of coronary intervention 4.81 h (2.85, 7.91). The time between symptom onset and initiation of both thrombolytic therapy and coronary intervention was significantly related to the global ejection fraction and to the extent of regional hypokinesia at the 3-month follow-up (p<0.05). The time to the initiation of GP IIb/IIIa inhibitors was only significantly related to the global ejection fraction (p<0.05), while the time to the first medical contact did not show a similar relationship (p>0.05). Furthermore, we observed a significant relationship between the infarct-related artery (IRA) patency at the initial angiogram and the residual regional myocardial damage at follow-up; normokinesia at follow- up was found in 61.3% of patients with an initially patent IRA and in 41.2% of patients with an initially occluded IRA, whereas severe hypokinesia was found in 13.8% and 37.3%, respectively (p<0.05).ConclusionIn patients with STEMI treated with a facili tated PCI strategy using half dose r-tPA in combination with a glycoprotein IIb/IIIa receptor blocker, the 3-month global and regional residual myocardial dysfunction is significantly related to the time elapsed between the onset of symptoms and the start of both fibrinolytic therapy and coronary intervention.

Intracoronary nisoldipine: Effects on acute myocardial ischemia during coronary angioplasty

SummaryThe effects on ischemic myocardium of 0.05 mg nisoldipine given by intracoronary injection were studied in 22 patients subjected to percutaneous transluminal coronary angioplasty. The angioplasty balloon was inflated for periods of 60 seconds. During the occlusion period, pulmonary wedge pressure was measured, an intracoronary epicardial ECG recorded, and ventricular volumes and ejection fraction were determined by means of digital subtraction angiography. After the intracoronary administration of nisoldipine, the onset of the rise in diastolic filling pressure was slightly delayed from 29 to 36 seconds. While affecting neither the rise in filling pressure nor the increase in end-diastolic and endsystolic volumes after 60 seconds of ischemia, nisoldipine delayed the occurrence (from 13 to 33 seconds; p<0.005) and reduced the extent (from 1.5 to 0.6 mV; p<0.001) of ischemic ST elevation in the intracoronary ECG. After nisoldipine, anginal symptoms were clearly reduced during the ischemic phase in the majority of patients. These findings suggest that intracoronary pretreatment with nisoldipine leads to a regional protection of ischemic myocardium without any appreciable effect on ischemia-induced myocardial dysfunction.

Protective effects of pretreatment with intracoronary nifedipine on myocardial ischemia and dysfunction

SummaryTo assess whether pretreatment with intracoronary nifedipine protects the myocardium against acute ischemia induced by coronary occlusion, 18 patients were studied during coronary angioplasty of the left anterior coronary artery. After a control occlusion of 60 seconds, 0.1 mg nifedipine was injected and occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary pressure was measured and the intracoronary epicardial ECG was recorded. After intracoronary administration of nifedipine, the onset of the rise in diastolic filling pressure was delayed from 23 to 38 seconds (p<0.01) and the changes at 60 seconds of occlusion were reduced from 14 to 11 mmHg (p<0.05). Nifedipine delayed the appearance of ischemic ST-segment elevation in the intracoronary ECG from 11 to 21 seconds (p<0.01) and diminished the changes at 60 seconds of occlusion from 1.8 to 1.2 mV (p<0.05). These findings suggest that pretreatment with intracoronary nifedipine protects the myocardium against some of the mechanical and electrocardiographic consequences of regional ischemia during acute coronary occlusion.

Late increase in luminal diameter of aortocoronary venous bypass grafts associated with an increase in the vascular region under supply

In a previous study, a significant inverse relation was found between the luminal size of aortocoronary venous bypass grafts and the vascular resistance of the coronary region that was perfused by the bypass graft in late stages after bypass surgery. This observation suggested that changes in the graft-dependent vascular area could influence the luminal size of the vein graft, even when they occurred several years after operation. Whereas it is well established today that aortocoronary vein grafts often decrease in luminal diameter after implantation, an increase in the bypass lumen has so far not been reported. Therefore, changes in luminal diameter of 27 vein grafts in 21 patients who underwent at least two postoperative angiographic studies (first study 8 +/- 5 months after surgery, second study 58 +/- 32 months after surgery) were compared with the size of the vascular region supplied by the bypass. The graft diameter was found to be unchanged between the two studies (3.3 +/- 0.6 versus 3.4 +/- 0.7 mm, p = NS) when the dependent vascular area was unchanged. A significant increase in graft diameter from 2.8 +/- 0.8 to 3.9 +/- 0.9 mm (p less than 0.001) was observed in nine patients in whom the area of perfusion had increased between the two studies because of the development of occlusion or obstruction of major coronary branches that were now perfused from the grafted vessel by way of collateral vessels. These data support the contention that the luminal size of aortocoronary vein grafts can adapt to the needs of the dependent myocardial vascular region even late after operation rather than being the result of a nonreversible degenerative process as commonly assumed.

Akutes Koronarsyndrom durch Diclofenac induzierte Koronarspasmen

We report about a 67-year old man, who was submitted to our clinic with acute coronary syndrome. The cardiac catheterization showed a proximal thrombus in the left anterior descending (LAD). The other coronary arteries did not have significant lesions. After percutaneous transluminal coronary angioplasty with stent-implantation into the proximal LAD the patient remained clinically stable. Cardiac enzymes confirmed no myocardial necrosis. Three days after the acute coronary syndrome the patient developed a podagra, which was treated with colchicinum, diclofenac and local cooling. Five hours after initial therapy the patient developed severe symptoms of angina pectoris and electrocardiographical signs of an acute posterior and anterior myocardial infarction. Immediate coronary angiography demonstrated extended vasospasm of the right coronary artery. Intracoronary application of verapamil and nitroglycerin resolved the coronary spasm. The patient reported about a self-indicated application of diclophenac six hours before hospital admission. This case demonstrates that oral application of diclofenac can provoke coronary vasospasm. Wir berichten über einen 67-jährigen Patienten, der mit dem Bild eines akuten Vorderwandmyokardinfarktes im Rahmen eines akuten Koronarsyndroms in die Klinik eingeliefert wurde. Die sofort durchgeführte Herzkatheteruntersuchung zeigte einen frischen Thrombus im proximalen Ramus interventrikularis anterior (RIVA) bei sonst unauffälligen Koronararterien. Nach PTCA mit Stent-Implantation in den proximalen RIVA war der Patient vollkommen beschwerdefrei. Die CK, CKMB sowie das Troponin T blieben im Normbereich. Im Verlauf entwickelte der Patient eine Podagra des rechten Großzehengrundgelenkes, welches mit Colchicin, Diclofenac und lokaler Kühlung behandelt wurde. Fünf Stunden nach Gabe von Colchicin sowie Diclofenac klagte der Patient über heftige Angina pectoris-Symptomatik mit elektrokardiographischen Zeichen eines akuten Hinterwand- und Vorderwandmyokardinfarktes. Eine erneute durchgeführte Herzkatheteruntersuchung zeigte ausgeprägte Vasospasmen der rechten Koronararterie. Nach intrakoronarer Verapamil- und Nitroglycerin-Gabe waren die Koronarspasmen deutlich rückläufig und der Patient war beschwerdefrei. Anamnestisch berichtete der Patient, dass er am Abend ca. 6 h vor dem akuten Koronarsyndrom ebenfalls Diclofenac eingenommen hätte. Bei zweimaliger in unmittelbarem Zusammenhang mit der Diclofenac-Einnahme stehenden akuten Koronarsymptomatik ist von einem Diclofenac induziertem Vasospasmus auszugehen.

The effects of pretreatment with nitroglycerin on ischemic left ventricular dysfunction during coronary angioplasty

SummaryTo evaluate the degree to which nitroglycerin reduces myocardial ischemia and dysfunction induced by transient coronary occlusion, 19 patients were studied during coronary angioplasty of the left anterior descending coronary artery. After a control occlusion of 60 seconds, 0.2 mg nitroglycerin was administered intravenously and the occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary wedge pressure was measured, the intracoronary ECG was recorded, and ventricular volumes, ejection fraction, and regional systolic shortening were obtained by digital subtraction angiography. Nitroglycerin caused a significant fall in pulmonary capillary wedge pressure before (10 vs. 7 mmHg) and at 60 seconds occlusion (18 vs. 14 mmHg), but did not significantly delay the rise in wedge pressure (37 vs. 44 seconds). Endsystolic left ventricular volume at 60 seconds of occlusion was reduced by nitroglycerin (77 vs. 68 ml), whereas regional shortening of the ischemic segments remained unchanged (22 vs. 23%). Nitroglycerin did not delay the onset of ischemic ST-segment elevation (14 vs. 14 seconds) and had no effect on the changes of ST elevation in the intracoronary ECG (1.9 vs. 1.9 mV).These findings suggest that intravenous nitroglycerin reduces filling pressure and slightly improves left ventricular global function during acute coronary occlusion. Nitroglycerin, however, has little effect on ischemia-induced regional dysfunction and on ST-segment elevation in the intracoronary ECG.

Reduced diastolic left ventricular posterior wall motion in patients with constrictive pericarditis — incidence, hemodynamic and clinical correlations

In 24 patients with constrictive pericarditis proven by cardiac catheterization, the amplitude of diastolic left ventricular posterior wall motion was evaluated by M-mode echocardiography and compared to the results of 24 healthy volunteers. The amplitude was significantly less in constrictive pericarditis patients than in normal controls (0.3 +/- 0.2 mm versus 3.9 +/- 0.4 mm) (P less than 0.001). No constrictive pericarditis patient demonstrated a higher value than 2 mm whereas none of the healthy volunteers had an amplitude less than 3 mm. In 11 of 13 constrictive pericarditis patients who underwent pericardiectomy, an increase in amplitude was observed. In 6 patients the amplitude returned to normal limits after surgery. No significant correlation between the degree of heart failure or the level of left ventricular end-diastolic pressure and the reduction of the amplitude was found. In addition, the amplitude of left ventricular diastolic posterior wall motion did not allow a clear separation between patients who could be treated medically and those requiring pericardiectomy.