["Cryptogenic" coronary embolism - Case 4/2011]. / "Kryptogene" Koronarembolie - Fall 4/2011.

HISTORY AND ADMISSION FINDINGS: We report on a 42-year-old patient who presented with acute chest pain which occurred during defaecation. History revealed no cardiovascular risk factors. INVESTIGATIONS: ECG and laboratory testing showed an non-ST-elevation myocardial infarction (NSTEMI). DIAGNOSIS, TREATMENT AND COURSE: Coronary angiography revealed an embolic occlusion of the ramus intermedius. As origin of the embolus a deep vein thrombosis and a persistent foramen ovale (PFO) was diagnosed. We occluded the PFO with an Amplatz occluder. Because of the traumatic deep vein thrombosis phenprocoumon and clopdiogrel were given for 6 months. CONCLUSIONS: Patients with no cardiovascular risk profile, who present with typical chest pain, an embolic cause is an important differential diagnosis. Especially history is very helpful for the correct diagnosis. Interventional occlusion of PFO is a simple and safe approach for patients with symptomatic PFO regarding no permanent antithrombotic medication.

Prevalence of aspirin resistance in patients with type 2 diabetes.

Aspirin resistance has been recognised to occur in patients with cardiovascular disease and is associated with poor clinical prognosis. The purpose of the present study was to evaluate the prevalence of aspirin resistance in 172 patients with diabetes mellitus type 2 (DM-2). Platelet function of 172 consecutive patients with type 2 diabetes on chronic aspirin therapy was evaluated. The effect of aspirin was assessed using the platelet function analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the time required to close a small aperture in a biologically active membrane. Resistance to aspirin was defined as a normal collagen/epinephrine-induced closure time (82-165 s). Aspirin responders were defined when closure time was > or =300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106 (61.6%) were responders. Univariate analysis revealed that aspirin non-responders were significantly younger (p<0.05) compared to aspirin responders. A significant number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin resistance can be evaluated by point-of-care testing and should be recognised in diabetic patients that are treated for primary or secondary prevention.

Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.

BACKGROUND: We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease. METHODS AND RESULTS: This study was a 12-month, open-label, randomized, multicenter trial, which used serial 3D intracoronary ultrasound to calculate plaque volume and plaque echogenicity. After transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86 mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care group. Mean absolute plaque volume showed a larger increase in the usual care group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3), atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the plaque increased to a larger extent for the atorvastatin group than for the usual care group, with a significant treatment effect for the percent change (atorvastatin 42.2%, usual care 10.1%; P=0.021). CONCLUSIONS: One year of lipid-lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque growth of minor lesions. The significantly larger increase in plaque hyperechogenicity is most likely due to a change in plaque composition.

Reproducibility of serial intravascular ultrasound measurements in patients with angiographically silent coronary artery disease after heart transplantation.

BACKGROUND: Intracoronary ultrasound (ICUS) imaging is the most sensitive method for the early detection and serial evaluation of vasculopathy of transplants. Both lack of agreement between observers and lack of agreement between serial, independent pullback procedures (repeatability), which can result in a variable intraluminal catheter position may limit the reproducibility of ICUS measurements. OBJECTIVE: To evaluate the reproducibility of serial measurements of standard linear and area cross-sectional coronary dimensions in patients with non-obstructive transplant vasculopathy. METHODS: We performed ICUS imaging of patients without angiographic evidence of obstructive epicardial coronary artery disease after heart transplantation. A 30 MHz phased-array transducer was used. Two independent pullbacks of the left anterior descending coronary artery were performed and recorded on CD-ROM for off-line quantitative analysis of the most severely diseased site. Agreement of observers and repeatability of serial measurements were calculated by the use of linear regression analysis and Bland-Altman plots. RESULTS: Regarding agreement of observers, correlation coefficients for intra-observer agreement ranged from r = 0.98 to r = 0.99; those for interobserver agreement ranged from r = 0.87 to r = 0.98. Serial measurements of the identical coronary artery cross-section within independent catheter pullback procedures were possible for 104 of 112 target lesions (92.90/%). Correlation coefficients ranged from r = 0.91 to r = 0.97 (for lumen diameter r = 0.91, for lumen area r = 0.93, for vessel diameter r = 0.91, for vessel area r = 0.97, for thickness of plaque r = 0.96 and for area of plaque 0.94). The mean difference of measurements was around zero for all parameters with SD from 0.13 to 0.4 mm for linear parameters and from 1.53 to 1.82 mm2 for area parameters. CONCLUSION: Serial intravascular ultrasound measurements are highly reproducible without any evidence of systematic error and a SD of differences of measurements beyond the maximal spatial resolution of currently available intravascular ultrasound catheters.

Medium-term results of heart transplantation using older donor organs.

BACKGROUND: Donor heart shortage has necessitated the expansion of the donor pool by the use of older hearts. PATIENTS AND METHODS: In a 13-year period, 1,070 heart transplants were performed in 1,035 adults at the German Heart Institute Berlin. We divided the patients into 3 groups: Group I, donor age <35 years (n = 524); Group II, donor age 35 to 50 years (n = 379); Group III, donor age >50 years (n = 167). We analyzed post-operative mortality (up to 30 days), cumulative survival rates, cardiac dependent morbidity, and changes in the left/right ventricular ejection fraction as well as freedom from cytomegalovirus infection and freedom from acute rejection episodes grade >/= 2 (International Society for Heart and Lung Transplantation). We also calculated the rate of cardiac interventions per patient in the groups. RESULTS: Recipients in Group III were significantly older, compared with Groups I and II. The post-operative mortality was 16.8% in Group I, 29.8% in Group II, and 23.4% in Group III. The differences were significant (p = 0. 00001) between Group I and Group II. The long-term cumulative survival rates were significantly better in Group I when compared with Groups II and III (p < 0.00001, p = 0.014), but it did not differ between Groups II and III (p = 0.18). However, cardiac morbidity in Groups I and II was significantly lower when compared with Group III (p = 0.0009, p = 0.037). Mean left and right ventricular ejection fraction was >55% and did not significantly change in groups for up to 10 years. Freedom from cytomegalovirus infection was not significantly different between Groups II and III (p = 0.09). Significantly fewer percutaneous transluminal coronary angioplasties were performed in Group I, but comparable numbers were carried out in Groups II and III (p = 0.53). For retransplantation a similar situation occurred. CONCLUSION: We did not find significant differences in the mid-term follow-up between patients who received hearts from 35- to 50-year-old donors and from those who had received hearts from donors >50 years, despite increased cardiac morbidity in Group III. Close monitoring of the coronary situation after heart transplantation and expanded indications for revascularization in Group III makes heart transplantation with older hearts a suitable option to save the lives of patients in end-stage heart failure.

Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy.

BACKGROUND: Transplant vasculopathy is the main limiting factor of the long-term success of heart transplantation. We sought to establish the role of platelets in the development and progression of transplant vasculopathy. METHODS AND RESULTS: Platelet analysis and intracoronary ultrasound examination were performed in 78 heart transplant recipients. Quantitative intracoronary ultrasound was used to define the severity of disease at baseline (48.8+/-4.5 months after transplantation) and at 1-year follow-up. Platelet activation was assessed with the use of immunological surface markers of activation (ligand-induced binding site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly increased in patients with diffuse disease when compared with focal transplant disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predictor for the presence and progression of diffuse transplant vasculopathy (P=0.04). Patients with enhanced LIBS-1 levels (>75% quartile) had a 3.3-fold increased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence of diffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1.9 and 12.5, P<0.01) for the progression of transplant vasculopathy. CONCLUSIONS: Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Understanding the underlying pathophysiological mechanisms might contribute to the development of treatment strategies to prevent transplant vasculopathy.

Electron-beam computed tomography in the assessment of coronary artery disease after heart transplantation.

BACKGROUND: Our aim was to compare the electron-beam CT (EBCT) features of coronary arteries in heart transplant recipients with those of biplane coronary angiography and intracoronary ultrasound (ICUS). METHODS AND RESULTS: We examined 112 heart transplant recipients (25 female; age, 17 to 69 years; median, 52 years) 1 to 153 months (median, 46 months) after surgery by EBCT to detect coronary artery calcifications. Calcifications were quantified by the Agatston scoring system. EBCT scores were compared with coronary angiography in all patients and ICUS of the left anterior descending coronary artery (LAD) in 100 patients. Coronary artery calcifications were found in 84 patients (75%). Angiographically, 16 patients displayed >50% coronary artery stenoses, all of whom had some degree of coronary artery calcification and only 1 of whom had a score of <55 (P<0.0001). With this threshold, EBCT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting stenosis. ICUS confirmed the presence of calcified plaques in all patients with an LAD score >9. EBCT total calcium score was associated with the degree of intimal proliferation in that patients without ICUS features of allograft vasculopathy had a median score of 0 (25th percentile, 0; 75th percentile, 0), whereas patients with Stanford class IV vasculopathy had a median score of 41 (9 to 98, P<0.0001). CONCLUSIONS: EBCT is a promising noninvasive test for the detection of coronary heart disease in cardiac transplant recipients.

[Influence of image quality on the diagnostic accuracy of dobutamine stress magnetic resonance imaging in comparison with dobutamine stress echocardiography for the noninvasive detection of myocardial ischemia]. / Einfluss der Bildqualität auf die Genauigkeit der nichtinvasiven Ischämiediagnostik mit der Dobutamin-Stressmagnetresonanztomographie im Vergleich zur Dobutamin-Stressechokardiographie.

The analysis of wall motion abnormalities with dobutamine stress echocardiography is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, the application of identical stress protocols as used for echocardiography is possible. In 208 consecutive patients (147 M, 61 F) with suspected coronary artery disease, dobutamine stress echocardiography partially using harmonic imaging and dobutamine stress magnetic resonance tomography (DSMR) were performed prior to cardiac catheterization. DSMR images were acquired during short breath holds in 3 short axis-, a 4-, and a 2-chamber view using a turbo gradient echo technique. Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16 segment model. Significant coronary heart disease was defined as angiographic >/=50% diameter stenosis. With DSMR, significantly more patients yielded very good (69%) or good (13%) image quality in comparison with dobutamine stress echocardiography (20% and 31%, p<0. 05). Moderate image quality occurred in 16% with MR and 41% with dobutamine stress echocardiography (p<0.05), 2% and 8% were non-diagnostic. With each technique 18 patients could not be examined (DSE: emphysema: 10, adipositas: 8, DSMR: claustrophobia: 11, adipositas: 6, contraindication: 1). Four patients did not reach target heart rate. In 107 patients, significant coronary artery disease was found. With DSMR sensitivity was 88.7% (dobutamine stress echocardiography: 74.3%; p<0.05) and specificity 85.7% (dobutamine stress echocardiography: 69.8%; p <0.05). This difference was most pronounced in the group with moderate echocardiographic image quality. High dose DSMR is superior to dobutamine stress echocardiography and can replace this technique especially in patients with moderate echocardiographic image quality.

Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography.

BACKGROUND: The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. METHODS AND RESULTS: In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. CONCLUSIONS: High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE.

Does dobutamine stress echocardiography induce damage during viability diagnosis of patients with chronic regional dysfunction after myocardial infarction?

Experimental hibernating-model investigations of animals have shown that myocardial necrosis can be induced by longer-term intracoronary dobutamine infusion. This study was designed to determine whether myocardial infarction could be ascertained in patients with chronic regional wall motion abnormalities and greater than 75% stenosis in the supplying coronary artery through dobutamine stress echocardiography. Twenty patients with coronary artery disease and regional resting wall motion abnormalities were examined with a standard dobutamine protocol (5 to 50 microg/kg/min). Exclusion criteria were an acute coronary syndrome, severe heart failure, and severe hypertension. Creatine kinase (CK, CKMB), myoglobin, and troponine-I were measured before and at each of the first 7 hours after beginning of infusion. Fourteen of these 20 patients exhibited viable myocardium. The serum markers CK, CKMB, myoglobin, and troponin-I demonstrated no increase beyond the reference range, suggesting that with this protocol, no myocardial necrosis was induced.

Safety of intracoronary ultrasound imaging in patients with acute myocardial infarction.

In 103 patients with acute myocardial infarction, intracoronary ultrasound imaging (ICUS) was performed before and after percutaneous transluminal coronary angioplasty (PTCA) with a pre-PTCA success rate of 79 of 103 patients (76.7%), post-PTCA rate of 88 of 103 patients (85.4%), and a reversible subacute occlusion rate after initial ICUS of 3.9%. Time consumption was 7 +/- 1 minute for pre-PTCA ICUS and 3 +/- 1 minute for post-PTCA ICUS.

Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease.

BACKGROUND: Graft coronary disease (GCD) remains the single greatest limitation to long-term survival of heart transplant recipients. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited; palliative coronary revascularization has been attempted. Because of the high mortality rate associated with advanced forms of GCD our institution offers the option of retransplantation in selected cases. The aim of this study was by analyzing retrospectively the outcomes of angioplasty, coronary bypass grafting, and retransplantation in cardiac transplant patients to attempt to identify subgroups of transplant recipients with graft coronary disease who may profit from myocardial revascularization. METHODS: Of the 989 patients undergoing 1016 heart transplantations (HTx) at our institution between 10/86 and 12/97, all were screened for the development of GCD. Analyzing routinely annual angiography, intracoronary ultrasound in defined study patients, and autopsy findings, GCD was diagnosed in 124 patients (110 male, 14 female) 2 to 107 months after HTx (mean 30 months). RESULTS: PTCA: Fourty-six out of 124 patients underwent 76 angioplasties at a mean of 50 +/- 30 months (range 4-91 mo) following cardiac transplantation. The primary success rate was 96% (73/76). The reason for the unsuccessful angioplasty attempts (n = 3) was failure to completely penetrate a stenosis of LAD in 2 patients and severe dissection of RCA, which required emergency surgery, in one. Angiographic restenosis occurred in 42% (31 of 76 lesions) and was diagnosed 11 +/- 11 months after the first angioplasty. There was no procedure-related death. CABG: Seven patients underwent bypass surgery at a mean of 67 months (range 6-128 months) after HTx. Elective surgery was performed in 2 patients with proximal severe triple-vessel disease (Type A lesion) and in 1 patient with severe tricuspid regurgitation who received a tricuspid valve replacement and concomitant single-vessel bypass surgery for proximal GCD (Type A lesion). One patient with combined Type A and B/C lesions required emergency surgery for dissection of RCA after an angioplasty procedure. Three patients with post-infarction unstable angina developed worsening congestive heart failure which required emergency surgery. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients and the patient with dissection of RCA were successfully treated and survived beyond hospital discharge (overall survival for CABG in GCD patients 4/7 = 57%). After a mean follow-up of 10 months (range 2-32 months) all are in good clinical condition. All 3 patients with distal arteriopathy and emergency surgery died in hospital of left-ventricular failure (43%). Retransplantation: Eight patients underwent retransplantation at a mean of 54 months (range 6-96 months) after HTx. Six of 8 patients had successful operations and survived beyond hospital discharge with a one-year-survival rate of 75%. In a mean follow-up of 31 months (5-68 months) 3 of 6 retransplant recipients developed a recurrence of GCD. CONCLUSION: The presence of angiographic distal arteriopathy should be considered a significant factor in patient selection for coronary revascularization procedure. Coronary angioplasty is to be considered as a method of treatment for severe, local stenoses (Type A lesion). PTCA may be applied in these selected cardiac transplant recipients with primary success and complication rates comparable to routine angioplasty but with an increased rate of restenosis especially in small vessels (diameter < 2.5 mm). The distinction between Type A lesions in large (diameter > or = 2.5 mm) and small vessels may be important not only with respect to restenosis but also with respect to long-term benefit. The overall survival did not differ between GCD patients with and without PTCA, suggesting this treatment to be largely palliative. (ABSTR

Stress echocardiography in special groups: in women, in left bundle branch block, in hypertension and after heart transplantation.

The non-invasive diagnosis of coronary artery disease by exercise electrocardiography is less accurate in women than in men, with a high rate of false-positive results in women. In contrast, recent studies have demonstrated that stress echocardiography in women is more accurate than exercise echocardiography and that the significantly higher specificity of stress electrocardiography may have the benefit of avoiding unnecessary angiography in women. Exercise-induced changes in the electrocardiogram are non-diagnostic in the presence of left bundle branch block or basal ST changes. In these patients, stress echocardiography can be used instead of conventional scintigraphy for the detection of coronary artery disease, but further echocardiographic studies are needed to confirm the promising results. Exercise electrocardiography and exercise echocardiography have been reported to be disappointing in the early detection of cardiac allograft vasculopathy after heart transplantation, and dobutamine stress echocardiography overestimates the incidence of angiographic evidence of cardiac allograft vasculopathy. However, compared to intravascular ultrasound imaging, dobutamine stress echocardiography seems to be a suitable non-invasive method for detecting cardiac allograft vasculopathy.

Intravascular ultrasound assessment of direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction is caused by sudden thrombotic occlusion of the coronary artery due to a previous rupture of atherosclerotic plaque. OBJECTIVE: To use intracoronary ultrasound measurements to evaluate lumen and plaque changes in patients with acute myocardial infarction. METHODS: Patients (n = 103) with acute myocardial infarction who had been scheduled to undergo primary percutaneous transluminal coronary angioplasty (PTCA) were selected. Both before and after successful coronary angioplasty, intracoronary 30 MHz ultrasound studies were performed using a 3.5F monorail catheter. The ultrasound catheter was successfully advanced into the occluded vessel segment without major complications prior to PTCA in 79 of 103 (76.7%) patients and after PTCA in 88 of 103 (85.3%) patients. RESULTS: The plaques were eccentric in 66 patients (83.5%). The plaque morphology was purely low echogenic in 14 (17.7%), highly echogenic in six (7.6%) and mixed in 59 (74.7%) patients. Partial (59 of 79, 74.7%) or ring-like calcification (3 of 79, 3.8%) was observed in 62 patients (78.5%). Plaque fissuring or dissection was detected prior to PTCA in 25 patients (31.7%). Coronary angioplasty successfully enlarged the inner luminal area from 2.1 +/- 0.7 to 7.4 +/- 1.9 mm2 (P < 0.01), whereas the plaque-thrombus area decreased significantly (13.8 +/- 1.7 mm2 before and 9.0 +/- 1.9 mm2 after PTCA; P < 0.01). The total vessel area remained virtually constant (15.9 +/- 1.9 mm2 before and 16.4 +/- 2.5 mm2 after PTCA, NS). PTCA-induced plaque rupture or dissection was observed in only 13 (16.5%) patients. CONCLUSION: Intracoronary ultrasound imaging can be performed safely and successfully prior and subsequent to PTCA in selected patients with acute myocardial infarction. Early reperfusion via PTCA seems to be attributable to a significant reduction in the amount of low-echogenic plaque and thrombus material, whereas factors like balloon-induced dissection and stretching of vessels play only a minor role.