Wolfgang Lepper

Assessment of Myocardial Reperfusion by Intravenous Myocardial Contrast Echocardiography and Coronary Flow Reserve After Primary Percutaneous Transluminal Coronary Angiography in Patients With Acute Myocardial Infarction

Background—This study investigated whether the extent of perfusion defect determined by intravenous myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction (AMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) relates to coronary flow reserve (CRF) for assessment of myocardial reperfusion and is predictive for left ventricular recovery. Methods and Results—Twenty-five patients with first AMI underwent intravenous MCE with NC100100 with intermittent harmonic imaging before PTCA and after 24 hours. MCE before PTCA defined the risk region and MCE at 24 hours the “no-reflow” region. The no-reflow region divided by the risk region determined the ratio to the risk region. CFR was assessed immediately after PTCA and 24 hours later. Left ventricular wall motion score indexes were calculated before PTCA and after 4 weeks. CFR at 24 hours defined a recovery (CFR ≥1.6; n=17) and a nonrecovery group (CFR <1.6; n=8). Baseline CFR did not differ between groups. M...

Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion

OBJECTIVES We sought to evaluate and compare recently suggested parameters of reperfusion after angioplasty in acute myocardial infarction (AMI) for risk stratification during long-term follow-up. BACKGROUND Abnormal myocardial perfusion has a detrimental impact on survival. Several parameters of reperfusion have been evaluated in controlled study populations for risk stratification. METHODS In 253 consecutive patients undergoing intervention in AMI on a native coronary vessel, angiographic myocardial blush grade (MBG), corrected TIMI (thrombolysis in myocardial infarction) frame count (CTFC) and persistent ST-segment elevation (STE) were determined to evaluate reperfusion. This was a high-risk population, including referral for treatment failure at a primary center in 29.2%, failed thrombolysis in 22.1% and cardiogenic shock in 13.4% of cases. RESULTS In addition to age, patient referral, LBBB and heart rate on admission, MBG 0 to 1 (odds ratio [OR] = 3.23, p < 0.001), CTFC (OR = 1.01, p = 0.015) and persistent STE >2 leads (OR = 3.46, p = 0.010) were univariate predictors of mortality during a 22.1 +/- 15.6 months follow-up. Myocardial blush grade 0 to 1 (OR = 2.17, p = 0.033) and persistent STE (OR = 3.61, p = 0.017) persisted as independent predictors of mortality, whereas CTFC failed. Differences in mortality between reperfusion groups at 30 days remained throughout the complete follow-up. In sequential Cox models, the predictive power of clinical data alone for mortality (model chi-squared 55.8) was strengthened by adding MBG (model chi-squared 64.2) and ECG postintervention (model chi-squared 69.2). CONCLUSIONS Myocardial blush grade 0 to 1 and persistent STE are independent predictors for long-term mortality after angioplasty in AMI. Corrected TIMI frame count is a less powerful predictor. Combining both parameters to consider quality of reperfusion in the myocardium at risk and extent of the infarct zone increases the predictive power.

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders

Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p < 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.

Transthoracic Echocardiography Using Second Harmonic Imaging Diagnostic Alternative to Transesophageal Echocardiography for the Detection of Atrial Right to Left Shunt in Patients With Cerebral Embolic Events

OBJECTIVES We sought to evaluate whether transthoracic contrast echocardiography using second harmonic imaging (SHI) is a diagnostic alternative to transesophageal contrast echocardiography (TEE) for the detection of atrial right to left shunt. BACKGROUND Paradoxic embolism is considered to be the major cause of cerebral ischemic events in young patients. Contrast echocardiography using TEE has proven to be superior to transthoracic echocardiography (TTE) for the detection of atrial shunting, SHI is a new imaging modality that enhances the visualization of echocardiographic contrast agents. METHODS We evaluated 111 patients with an ischemic cerebral embolic event for the presence of atrial right to left shunt using an intravenous (IV) contrast agent in combination with three different echocardiographic imaging modalities: 1) TTE using fundamental imaging (FI); 2) TTE using SHI; and 3) TEE. The severity of atrial shunting and the duration of contrast visibility within the left heart chambers were evaluated for each imaging modality. Image quality was assessed separately for each modality by semiquantitative scoring (0 = poor to 3 = excellent). Presence of atrial right to left shunt was defined as detection of contrast bubbles in the left atrium within the first three cardiac cycles after contrast appearance in the right atrium either spontaneously or after the Valsalva maneuver. RESULTS A total of 57 patients showed evidence of atrial right to left shunt with either imaging modality. Fifty-one studies were positive with TEE, 52 studies were positive with SHI, and 32 were positive with FI (p<0.001 for FI vs. SHI and TEE). The severity of contrast passage was significantly larger using SHI (61.6+/-80.2 bubbles) compared to FI (53.7+/-69.6 bubbles; p<0.005 vs. SHI) but was not different compared to TEE (43.9+/-54.3 bubbles; p = NS vs. SHI). The duration of contrast visibility was significantly longer for SHI (17.4+/-12.4 s) compared to FI (13.1+/-9.7 s; p<0.001) and TEE (11.9+/-9.6 s; p<0.02). Mean image quality improved significantly from FI (1.5+/-0.8) to SHI (2.0+/-0.8; p<0.001 vs. FI) and TEE (2.5+/-0.7; p<0.001 vs. SHI). CONCLUSIONS In combination with IV contrast injections, TEE and SHI have a comparable yield for the detection of atrial right to left shunt. Both modalities may miss patients with atrial shunting. In young patients with an unexplained cerebrovascular event and no clinical evidence of cardiac disease, a positive SHI study may obviate the need to perform a TEE study to search for cardiac sources of emboli.

Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function

This study evaluated recently suggested invasive and noninvasive parameters of myocardial reperfusion after acute myocardial infarction (AMI), assessing their predictive value for left ventricular function 4 weeks after AMI and reperfusion defined by myocardial contrast echocardiography (MCE). In 38 patients, angiographic myocardial blush grade, corrected Thrombolysis In Myocardial Infarction frame count, ST-segment elevation index, and coronary flow reserve (n = 25) were determined immediately after primary percutaneous transluminal coronary angioplasty (PTCA) for first AMI, and intravenous MCE was determined before, and at 1 and 24 hours after PTCA to evaluate myocardial reperfusion. Results were related to global wall motion index (GWMI) at 4 weeks. MCE 1 hour after PTCA showed good correlation with GWMI at 4 weeks (r = 0.684, p <0.001) and was in an analysis of variance the best parameter to predict GWMI 4 weeks after AMI. The ST-segment elevation index was close in its predictive value. Considering only invasive parameters of reperfusion myocardial blush grade was the best predictor of GWMI at 4 weeks (R(2) = 0.3107, p <0.001). A MCE perfusion defect size at 24 hours of > or =50% of the MCE perfusion defect size before PTCA was used to define myocardial nonreperfusion. In a multivariate analysis, low myocardial blush grade class was the best predictor of nonreperfusion defined by MCE. Thus, intravenous MCE allows better prediction of left ventricular function 4 weeks after AMI than other evaluated parameters of myocardial reperfusion. Myocardial blush grade is the best predictor of nonreperfusion defined by MCE and is the invasive parameter with the greatest predictive value for left ventricular function after AMI. Coronary flow parameters are less predictive.

Repeated Assessment of Coronary Flow Velocity Pattern in Patients With First Acute Myocardial Infarction

OBJECTIVES The aim of this study was to evaluate the coronary blood flow velocity pattern immediately and 24 h after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) in relation to myocardial reperfusion and follow-up left ventricular (LV) function. BACKGROUND Analysis of coronary blood flow velocity pattern after AMI may provide information about microvascular damage and the occurrence of a reperfusion injury. METHODS Measurement of coronary blood flow velocity pattern was performed immediately after PTCA and after 24 h in 25 patients with first AMI using a Doppler guidewire. Measurements were related to reperfusion determined by intravenous myocardial contrast echocardiography (MCE) performed before PTCA and at 24 h and to LV function at four weeks. RESULTS Using MCE, 13 patients showed reperfusion and 12 patients showed nonreperfusion. Compared with patients with reperfusion, patients with MCE nonreperfusion had a lower systolic peak flow velocity immediately after PTCA (10.0 +/- 0.3 cm/s vs. 19.3 +/- 0.8 cm/s, respectively) and after 24 h (12.3 +/- 0.4 cm/s vs. 21.3 +/- 0.1 cm/s, respectively, p = 0.0022), more frequent early systolic retrograde flow (6/12 vs. 0/13, p = 0.0052 immediately after PTCA and 24 h later) and a shorter diastolic deceleration time immediately after PTCA (483 +/- 6 ms vs. 737 +/- 0 ms, respectively) and after 24 h (551 +/- 9 ms vs. 823 +/- 2 ms, respectively, p = 0.0091). Similarly, patients with impaired LV function at four weeks had altered coronary flow pattern compared with patients with preserved function. The coronary flow velocity pattern showed a tendency for improvement after 24 h in the reperfusion and the nonreperfusion groups. CONCLUSIONS The coronary flow velocity pattern immediately and 24 h after PTCA for AMI relates to myocardial perfusion determined by MCE and LV function at four weeks. The flow velocity pattern shows slight improvement during the first 24 h after revascularization, indicating the absence of a major reperfusion injury.

Comparison of the 6-minute walk test with established parameters for assessment of cardiopulmonary capacity in adults with complex congenital cardiac disease

BACKGROUND Objective assessment of the cardiopulmonary capacity in patients with complex congenital cardiac disease often remains difficult in clinical practice. The cardiopulmonary exercise test and determination of the levels of brain natriuretic peptide in the plasma are established tests, but expensive. The 6-minute walk test is also validated, but has not often been used in patients with heart failure due to congenital heart disease, nor compared with other tests. We sought to compare its value with the results of cardiopulmonary exercise testing and measuring the levels of brain natriuretic peptide in the plasma. METHODS We carried out a standardized 6-minute walk test in 31 patients with complex congenital cardiac disease on the same day that they underwent cardiopulmonary exercise testing and determination of levels of brain natriuretic peptide in the plasma. Of the patients, 7 had functionally univentricular hearts, 9 had transposition, 9 had tetralogy of Fallot, 3 had common arterial trunk, and 3 had pulmonary atresia with intact interventricular septum. Uptakes of oxygen at peak exercise, and at the anaerobic threshold, were determined using cardiopulmonary exercise testing, and classified as suggested by Weber. The 6-minute walk test was performed according to a standard protocol. RESULTS There was a significant correlation between brain natriuretic peptide, oxygen uptakes at peak exercise and 6-minute walk. The correlation between the 6-minute walk test and oxygen uptakes at the anaerobic threshold, however, was not significant. CONCLUSIONS The 6-minute walk test can be performed easily, is inexpensive, widely available, and correlates well with measurements of brain natriuretic peptide and cardiopulmonary exercise testing, even in patients with corrected or palliated congenital cardiac malformations. A cut-off value of 450 metres in the 6-minute walk test allows a semi-quantitative classification in analogy to the classification suggested by Weber for cardiopulmonary exercise testing, and to a level of brain natriuretic peptide in the plasma of less or more than 100 picograms per millilitre.

Serial measurements of whole blood nitrite in an intensive care setting.

Nitrite plays an eminent role in cardiovascular physiology and pathology, mediating hypoxic vasodilation, reducing ischemia-reperfusion injury, and regulating cardiac energetics and function. The role of circulating nitrite in critically ill patients has not been examined so far. To investigate whether whole blood nitrite can be determined reproducibly in an intensive care setting, 30 patients from a cardiology intensive care unit were enrolled in this study, no matter what the underlying disease. Blood was drawn from an arterial catheter and whole blood nitrite was determined, using a tri-iodide/ozone-based chemiluminescence assay after incubation with a ferricyanide-containing stabilization solution. Whole blood nitrite levels ranged from 35 to 1193 nmol/L (mean+/-SEM: 220+/-20 nmol/L). Myocardial infarction was associated with lower whole blood nitrite levels (200+/-53 nmol/L for elevated serum CK MB levels vs 432+/-95 nmol/L in the normal CK MB range, p=0.039). Neither impaired kidney function nor an inflammatory state was associated with higher or lower whole blood nitrite levels. In conclusion, whole blood nitrite can be measured easily and reproducibly in critically ill patients, regardless of renal function and inflammation. The origin of decreased nitrite levels in myocardial infarction is currently unclear and needs to be further elucidated.

Improved endocardial border delineation during dobutamine stress echocardiography using the left heart contrast agent BY 963

The interpretation of induced wall motion abnormalities during dobutamine stress echocardiography is affected in the case of impaired image quality. In 48 consecutive patients (mean age 62±9 years, 32 males, 16 females) with suspected coronary disease undergoing coronary angiography, the transpulmonary contrast agent BY 963 was given i.v. as bolus during dobutamine stress echocardiography (10–40μgkgmin, plus max. 1mg atropine) to analyze improvements in endocardial border delineation. For each of the 16 segments of the left ventricle, the endocardial border delineation was evaluated. Using BY 963 the average number of non-evaluable segments decreased by 58% from 5.2% to 2.2% at rest (p=0.008) and by 56% from 5.9% to 2.6% at maximal stress (p=0.003) as compared to the non-contrast study for all patients. In patients with impaired image quality, defined as at least 1 non-evaluable segment at rest without contrast enhancement (N=14), the number of non-evaluable segments decreased from 19.2% to 8.2% (p=0.004) at rest and from 19.2% to 9.6% (p=0.006) at maximal stress. The greatest decrease of non-evaluable segments was seen in the lateral and anterior segments of the apical views (maximum of 80%). The improved endocardial border delineation resulted in an improved agreement between two observers in the interpretation of the dobutamine stress echocardiograms as positive or negative (kappa=0.38 without contrast, kappa=0.58 with contrast). Contrast application resulted in a slight improvement of diagnostic accuracy of dobutamine stress echocardiography in the detection of angiographically proven significant coronary artery disease. Conclusion: In patients with impaired endocardial border delineation the use of the echo contrast agent BY 963 reduces the number of non-evaluable segments. Improvement of endocardial delineation is greatest for lateral and anterior segments in the apical views. Die Interpretation induzierter Wandbewegungsstörungen während der Dobutamin-Belastungsechokardiographie ist bei einem Teil der Patienten durch unzureichende Endokardabgrenzbarkeit beeinträchtigt. Bei 48 konsekutiven Patienten (mittleres Alter 62±9 Jahre, 32 Männer, 16 Frauen) mit vermuteter koronarer Herzkrankheit, bei denen die Indikation zur Koronarangiographie gestellt worden war, wurde untersucht ob die intravenöse Applikation des lungengängigen Echokontrastmittels BY 963 eine verbesserte Endokarderkennbarkeit im linken Ventrikel sowohl in Ruhe als auch unter Dobutaminbelastung (10 bis 40μg/kg/min + maximal 1mg Atropin) erlaubt. Für jedes der 16 linksventrikulären Segmente wurde die endokardiale Erkennbarkeit beurteilt. Durch Einsatz des Kontrastmittels BY 963 ließ sich die durchschnittliche Zahl nicht-auswertbarer Segmente um 58% von 5,2% auf 2,2% in Ruhe (p=0,008) und um 56% von 5,9% auf 2,6% unter maximaler Belastung (p=0,003) senken. Bei Patienten mit eingeschränkter Bildqualität (N=14), definiert als fehlende Beurteilbarkeit mindestens eines Wandsegmentes in Ruhe, konnte die durchschnittliche Zahl nicht-auswertbarer Segmente von 19,2% auf 8,2% (p=0,004) vor Belastung und von 19,2% auf 9,6% (p=0,006) unter maximaler Belastung gesenkt werden. Die größte Abnahme nicht-auswertbarer Segmente zeigte sich in den lateralen und anterioren Segmenten der apikalen Schnittebenen (maximal um 80%). Die verbesserte endokardiale Abgrenzbarkeit resultierte in einer größeren Übereinstimmung zwischen zwei Untersuchern in der Bewertung der Dobutamin-Belastungsechokardiogramme als normal oder pathologisch (Kappa=0,38 ohne Kontrast, Kappa=0,58 mit Kontrast). Die diagnostische Genauigkeit der Dobutamin-Belastungsechokardiographie in der Erfassung einer angiographisch signifikanten koronaren Herzkrankheit stieg geringfügig an. Schlußfolgerung: Bei Patienten mit eingeschränkter Endokarderkennbarkeit führt der Einsatz des Echokontrastmittels BY 963 zu einer verminderten Zahl nicht-auswertbarer Segmente, wobei die Verbesserung in den lateralen und anterioren Segmenten der apikalen Schnittebenen am ausgeprägtesten ist.

Verbesserte Endokarderkennung der Dobutamin-Belastungsechokardiographie durch Einsatz des Linksherzkontrastmittels BY 963

The interpretation of induced wall motion abnormalities during dobutamine stress echocardiography is affected in the case of impaired image quality. In 48 consecutive patients (mean age 62±9 years, 32 males, 16 females) with suspected coronary disease undergoing coronary angiography, the transpulmonary contrast agent BY 963 was given i.v. as bolus during dobutamine stress echocardiography (10–40μgkgmin, plus max. 1mg atropine) to analyze improvements in endocardial border delineation. For each of the 16 segments of the left ventricle, the endocardial border delineation was evaluated. Using BY 963 the average number of non-evaluable segments decreased by 58% from 5.2% to 2.2% at rest (p=0.008) and by 56% from 5.9% to 2.6% at maximal stress (p=0.003) as compared to the non-contrast study for all patients. In patients with impaired image quality, defined as at least 1 non-evaluable segment at rest without contrast enhancement (N=14), the number of non-evaluable segments decreased from 19.2% to 8.2% (p=0.004) at rest and from 19.2% to 9.6% (p=0.006) at maximal stress. The greatest decrease of non-evaluable segments was seen in the lateral and anterior segments of the apical views (maximum of 80%). The improved endocardial border delineation resulted in an improved agreement between two observers in the interpretation of the dobutamine stress echocardiograms as positive or negative (kappa=0.38 without contrast, kappa=0.58 with contrast). Contrast application resulted in a slight improvement of diagnostic accuracy of dobutamine stress echocardiography in the detection of angiographically proven significant coronary artery disease. Conclusion: In patients with impaired endocardial border delineation the use of the echo contrast agent BY 963 reduces the number of non-evaluable segments. Improvement of endocardial delineation is greatest for lateral and anterior segments in the apical views. Die Interpretation induzierter Wandbewegungsstörungen während der Dobutamin-Belastungsechokardiographie ist bei einem Teil der Patienten durch unzureichende Endokardabgrenzbarkeit beeinträchtigt. Bei 48 konsekutiven Patienten (mittleres Alter 62±9 Jahre, 32 Männer, 16 Frauen) mit vermuteter koronarer Herzkrankheit, bei denen die Indikation zur Koronarangiographie gestellt worden war, wurde untersucht ob die intravenöse Applikation des lungengängigen Echokontrastmittels BY 963 eine verbesserte Endokarderkennbarkeit im linken Ventrikel sowohl in Ruhe als auch unter Dobutaminbelastung (10 bis 40μg/kg/min + maximal 1mg Atropin) erlaubt. Für jedes der 16 linksventrikulären Segmente wurde die endokardiale Erkennbarkeit beurteilt. Durch Einsatz des Kontrastmittels BY 963 ließ sich die durchschnittliche Zahl nicht-auswertbarer Segmente um 58% von 5,2% auf 2,2% in Ruhe (p=0,008) und um 56% von 5,9% auf 2,6% unter maximaler Belastung (p=0,003) senken. Bei Patienten mit eingeschränkter Bildqualität (N=14), definiert als fehlende Beurteilbarkeit mindestens eines Wandsegmentes in Ruhe, konnte die durchschnittliche Zahl nicht-auswertbarer Segmente von 19,2% auf 8,2% (p=0,004) vor Belastung und von 19,2% auf 9,6% (p=0,006) unter maximaler Belastung gesenkt werden. Die größte Abnahme nicht-auswertbarer Segmente zeigte sich in den lateralen und anterioren Segmenten der apikalen Schnittebenen (maximal um 80%). Die verbesserte endokardiale Abgrenzbarkeit resultierte in einer größeren Übereinstimmung zwischen zwei Untersuchern in der Bewertung der Dobutamin-Belastungsechokardiogramme als normal oder pathologisch (Kappa=0,38 ohne Kontrast, Kappa=0,58 mit Kontrast). Die diagnostische Genauigkeit der Dobutamin-Belastungsechokardiographie in der Erfassung einer angiographisch signifikanten koronaren Herzkrankheit stieg geringfügig an. Schlußfolgerung: Bei Patienten mit eingeschränkter Endokarderkennbarkeit führt der Einsatz des Echokontrastmittels BY 963 zu einer verminderten Zahl nicht-auswertbarer Segmente, wobei die Verbesserung in den lateralen und anterioren Segmenten der apikalen Schnittebenen am ausgeprägtesten ist.