ABSTRACT
BACKGROUND: Optimization of AV and VV delay programming has been shown to be essential for the success of cardiac resynchronization therapy (CRT). Acute hemodynamic improvement can be obtained by intracardiac electrocardiogram (IEGM)-based optimization. The aim of the present study was to evaluate whether this IEGM-based algorithm is comparable to the current gold standard of echocardiography. METHODS: After device implantation patients with standard criteria for CRT, AV and VV delay programming was either optimized by an IEGM-based algorithm (IEGM group, n = 24) or by echocardiography (echo group, n = 24). Cardiopulmonary exercise capacity was assessed after 3 and 12 months on the basis of NYHA class and the 6-min-walk test. Left ventricular ejection fraction was evaluated by echocardiography. RESULTS: In both groups there was a significant decrease in NYHA class and a significant increase in 6-min-walk distance and ejection fraction after 3 and 12 months. After 12 months there was no significant difference in the proportion of responders, NYHA class and 6-min-walk distance between the IEGM the echo group. CONCLUSION: The present data show that a sustained improvement of cardiopulmonary exercise capacity can be obtained by optimizing CRT patients on the basis of an IEGM algorithm. The comparable results for cardiopulmonary exercise parameters suggest that this new method might become an important tool for adjusting CRT programming in daily practice.
Subject(s)
Cardiac Resynchronization Therapy/methods , Echocardiography/methods , Electrocardiography/methods , Heart Failure/therapy , Signal Processing, Computer-Assisted , Aged , Algorithms , Bundle-Branch Block/mortality , Bundle-Branch Block/physiopathology , Bundle-Branch Block/therapy , Cardiac Resynchronization Therapy Devices , Echocardiography/instrumentation , Electrocardiography/instrumentation , Electrodes, Implanted , Equipment Design , Exercise Test , Female , Follow-Up Studies , Heart Atria/physiopathology , Heart Failure/mortality , Heart Failure/physiopathology , Heart Ventricles/physiopathology , Hemodynamics/physiology , Humans , Male , Middle Aged , Signal Processing, Computer-Assisted/instrumentation , Software , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: High-dose dobutamine stress magnetic resonance (DSMR) is a well-established imaging technique for the detection of coronary artery disease (CAD). PURPOSE: To investigate the value of DSMR for the detection of in-stent restenoses (ISR) in patients with prior coronary stenting, using invasive coronary angiography (ICA) as the standard of reference. MATERIAL AND METHODS: 50 patients with 74 stents and without wall motion abnormalities at rest were examined on a 1.5T MR scanner and underwent ICA for clinical reasons within 14 days after DSMR examination. A dobutamine/atropine stress protocol was employed until age-predicted heart rate was achieved, and imaging was performed in at least three long- and three short-axis views using a segmented steady-state free precession sequence (repetition/echo time [TR/TE] 3/1.5 ms, flip angle 60 degrees). All examinations were read by an experienced cardiologist and radiologist in consensus, with myocardial ischemia being defined as a new stress-induced wall motion abnormality in at least one myocardial segment. Statistical analysis was performed on a per-vessel (left circumflex artery [LCX], left anterior descending artery [LAD], and right coronary artery [RCA]) basis and with regard to the number of affected vessels (one-, two- or three-vessel disease). RESULTS: ICA yielded seven ISR, of which one was missed by DSMR (sensitivity 86%, 95% confidence interval [CI] 0.42-0.99). Sixty-seven coronary arteries showed no ISR in ICA; however, due to new wall motion abnormalities, seven ISR were suspected in DSMR (2xRCA, 3xLCX, and 2xLAD; sensitivity 86%, specificity 90%, positive predictive value 46%, negative predictive value 98%, and diagnostic accuracy 89%). The per-vessel analysis of the three main coronary arteries revealed highest sensitivity (100%), specificity (93%), and diagnostic accuracy (94%) for the LAD. CONCLUSION: High-dose DSMR is an accurate, noninvasive technique for the detection of ISR and reliably allows identification of patients who need to undergo control ICA.
Subject(s)
Cardiotonic Agents , Coronary Restenosis/diagnosis , Dobutamine , Magnetic Resonance Imaging/methods , Stents , Adult , Aged , Contrast Media , Coronary Angiography , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
BACKGROUND: Patients with internal carotid artery (ICA) stenosis have an increased incidence of coronary heart disease. Evidence about the incidence of clinically silent myocardial infarction (MI) in these patients is limited. Contrast-enhanced cardiac magnetic resonance (CMR) imaging allows for the detection of minor myocardial damage. OBJECTIVE: We tested whether patients with ICA stenosis exhibit a relevant incidence of silent MI when assessed by CMR. METHODS: In a single-center study, 77 consecutive patients (age 68 +/- 7 years) with suspected ICA stenosis were imaged prospectively with a combined MRI protocol including T(1), T(2), diffusion-weighted imaging, fluid-attenuated inversion recovery, and contrast-enhanced MR angiography (CEMRA) imaging of the brain and a short (11 min) CMR protocol with left ventricular function and late gadolinium enhancement imaging. Blinded to any clinical information, two readers evaluated the cardiac and neuroradiologic examinations. RESULTS: Of 154 imaged ICA, 85 presented with stenosis and 17 were occluded. In 7 patients, the suspected ICA stenosis could not be confirmed by CEMRA. In the remaining 70 patients with ICA stenosis, 34.3% had cerebral lesions (15.7% with a homodynamic pattern,18.6% with territorial infarction). CMR detected MI in 29 (41%) patients, whereas ECG and medical history enabled diagnosis in only 7 (10%) patients. CONCLUSIONS: ICA stenosis patients have a higher incidence of myocardial scars proving silent MI when detected by contrast-enhanced CMR than clinically expected. Whether the presence and extent of silent MIs detected by CMR affect peri-interventional risk and prognosis of ICA stenosis patients remains to be evaluated in a large patient cohort with long-term follow-up.
Subject(s)
Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Myocardial Infarction/complications , Myocardial Infarction/pathology , Myocardium/pathology , Aged , Carotid Stenosis/diagnosis , Electrocardiography , Female , Gadolinium , Humans , Incidence , Magnetic Resonance Angiography , Magnetic Resonance Imaging/methods , Male , Middle Aged , Myocardial Infarction/epidemiology , Prospective Studies , Sensitivity and Specificity , Single-Blind Method , UltrasonographyABSTRACT
BACKGROUND: Aortic valve stenosis is the most common type of valve lesion in Europe and North America. Patient treatment is based on disease severity, which is classified by determining the aortic valve area (AVA). PURPOSE: To compare dual-source computed tomography (DSCT) with magnetic resonance (MR) imaging for quantifying AVA. MATERIAL AND METHODS: Thirty-two patients, 28 with normal aortic valve function and four with aortic valve stenosis, who underwent DSCT coronary angiography (Somatom Definition; Siemens, Erlangen, Germany), were included in this study. Retrospective ECG-gated contrast-enhanced DSCT scans with dose-reducing tube current modulation were performed, and data sets were reconstructed in 3% steps of the R-R interval (slice thickness 0.75 mm, increment 0.6 mm). Planimetry of the AVA in systole was assessed on cross-sectional images by multiplanar reformations. Within 48 hours, MR was performed with a 1.5T scanner (Magnetom Sonata; Siemens, Erlangen, Germany) using a balanced steady-state free-precession cine sequence (repetition/echo time 3/1.5 ms, flip angle 60 degrees, spatial resolution 1.4 x 1.4 mm(2)). Cine sequences of the left ventricular outflow tract (LVOT) were obtained in two orthogonal planes, and MR planimetry was performed on cross-sectional images of the aortic valve perpendicular to the LVOT images. RESULTS: AVA assessment by DSCT and MR was feasible in all 32 patients. Mean AVA values determined by DSCT and MR were 4.73+/-1.5 cm(2) and 4.69+/-1.4 cm(2), respectively. A strong positive correlation was found between both imaging modalities (R=0.98, P<0.001). Bland-Altman analysis demonstrated an excellent intermodality agreement, with a slight underestimation of AVA by DSCT. The mean difference was -0.04 cm(2), with a standard deviation of 0.32 cm(2). CONCLUSION: Retrospective ECG-gated contrast-enhanced DSCT with tube current modulation provides an accurate imaging technique for the assessment of the AVA. Further studies are required to determine whether DSCT also allows for AVA quantification in patients with aortic valve stenosis.
Subject(s)
Aortic Valve Stenosis/diagnosis , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/pathology , Contrast Media , Electrocardiography , Feasibility Studies , Female , Humans , Male , Middle Aged , Radiographic Image Enhancement/methods , Reproducibility of Results , Retrospective Studies , Severity of Illness Index , Triiodobenzoic AcidsSubject(s)
Critical Care/standards , Emergency Service, Hospital/standards , Cardiovascular Diseases/mortality , Cardiovascular Diseases/therapy , Critical Care/organization & administration , Emergency Service, Hospital/organization & administration , Germany , Humans , Respiratory Insufficiency/mortality , Respiratory Insufficiency/therapy , Time Factors , WorkforceABSTRACT
Sudden cardiac death related to sports in young patients can have many causes. Hypertrophic cardiomyopathy, congenital coronary abnormalities, and myocarditis make up about half of the causes of sudden cardiac death after sports. Screening for all athletes is important to prevent such episodes. This involves yearly examinations including clinical examinations, stress echocardiograms, echocardiography, and laboratory investigations. Also, behavioral follow up should be addressed, as cocaine administration and doping can both lead to cardiac problems and sudden cardiac death after sports. We present a case of a 17-year-old boy who collapsed after an ice hockey competition as a result of an acute myocardial infarction, which was first represented by ventricular fibrillation. We also review the main causes of sudden cardiac death in such young athletes and the main investigations that have to be performed to reach the proper diagnosis and etiology of the condition.
Subject(s)
Myocardial Infarction/etiology , Adolescent , Death, Sudden, Cardiac/etiology , Hockey/injuries , Humans , Male , Myocardial Infarction/therapyABSTRACT
This paper reports in detail on a project of Integrated Health Care in cardiology at Essen, Germany. Information on the structure of the contract, the participants, the agreed claiming of benefits and provision of services are provided as well as relevant figures and contact data.
Subject(s)
Cardiology/trends , Delivery of Health Care, Integrated/organization & administration , Contracts/trends , Delivery of Health Care, Integrated/economics , Germany , Heart Diseases/therapy , Humans , Practice Guidelines as Topic , Program DevelopmentABSTRACT
PURPOSE: Transthoracic echocardiography is the routine diagnostic procedure in assessing patients with left ventricular thrombi, but is limited by the acoustic window and poor contrast between thrombus and adjacent myocardium. This study evaluates the role of cardiac MRI in the detection of left ventricular thrombi in patients with chronic myocardial infarction compared to standard transthoracic echocardiography. MATERIALS AND METHODS: In 82 patients (55 men and 27 women, age 36 to 79 years, median 59 +/- 11 years) who suffered a myocardial infarction more than 6 months earlier, transthoracic echocardiography and MRI were performed. The MRI protocol included steady state cine imaging (true FISP: TR 3.0 ms, TE 1.5 ms, FA 65 degrees ) in standard long and short axis orientation and contrast-enhanced imaging using a 3D IR-FLASH sequence with long inversion time (TR 4 ms, TE 1.43 ms, FA 10 degrees , TI 300 ms) early, and a 2D IR-FLASH sequence with optimized inversion time (TR 8 ms, TE 4.3 ms, FA 20 degrees , TI 180 - 280 ms) late after administration of gadolinium. RESULTS: Transthoracic echocardiography depicted 12 thrombi. Contrast-enhanced MRI confirmed these 12 thrombi and detected 23 additional thrombi. With the exception of 2 very small apical thrombi only visible on contrast-enhanced MR images, spherical thrombi were diagnosed by both techniques, whereas only contrast-enhanced MRI was able to visualize mural thrombi. Left ventricular thrombi were more frequently diagnosed in patients with moderate to severe impairment of the left ventricular systolic function, 32/42 (76 %), or in patients with left ventricular aneurysms, 21/24 (84 %). CONCLUSION: Contrast-enhanced MRI is mostly superior to transthoracic echocardiography in diagnosing mural left ventricular thrombi in patients who had suffered a myocardial infarction. Intracavitary thrombi are more frequently found in patients with impaired regional and global left ventricular function.
Subject(s)
Echocardiography , Heart Diseases/diagnostic imaging , Heart Diseases/diagnosis , Heart Ventricles , Magnetic Resonance Imaging , Thrombosis/diagnostic imaging , Thrombosis/diagnosis , Adult , Aged , Chronic Disease , Contrast Media , Echocardiography/methods , Electrocardiography , Female , Gadolinium DTPA , Heart Aneurysm/diagnosis , Heart Ventricles/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Myocardial Infarction/complications , Time Factors , Ventricular Dysfunction, Left/complicationsABSTRACT
The German "GKV-Modernisierungsgesetz" offers new opportunities for patient care. The concept of "integrated care" provides organizational structures for an standardized treatment of myocardial infarction by bridging the different sectors of the German health care system. Apart from guideline-based therapy, innovative diagnostic (cardiac MRI) and therapeutic (drug-eluting stents) techniques are implemented in the "integrated care" model as well. The "Herzinfarktverbund Essen" is the first national real world experience of the integrated care concept in the treatment of myocardial infarction.
Subject(s)
Delivery of Health Care, Integrated/organization & administration , Myocardial Infarction/therapy , National Health Programs/organization & administration , Diffusion of Innovation , Germany , Health Plan Implementation/organization & administration , Humans , Myocardial Infarction/diagnosis , Practice Guidelines as TopicABSTRACT
AIM: Purpose of our study was to compare the image quality of 3D-navigator steady state free precession (SSFP) and gradient echo (GE) sequences for magnetic resonance coronary angiography (MRCA) in volunteers and patients. METHODS: Following informed consent 8 volunteers and 12 patients were included into this study. In all subjects a 3D navigator MRCA of the right and the left coronary artery was performed with a SSFP (TR 3.9 ms, TE 1.7 ms, FA 65 degrees, bandwidth 540 Hz) and a GE (TR 5.8 ms, TE 2.2 ms, FA 25 degrees, bandwidth 200 Hz) sequence using a 1.5 T-MR-System (Magnetom Sonata, Siemens Erlangen). The slice thickness was 1.5 mm and the in-plane resolution was 0.9 x 0.7 mm (2) for all measurements. RESULTS: The blood pool showed a significantly (p < 0.01) higher signal intensity on SSFP images (147 +/- 36) compared to GE images (103 +/- 36). Although noise increased with SSFP (9.3 +/- 1.4 versus 5.3 +/- 0.9), the contrast-to-noise ratio between myocardium and the coronaries was significantly (p < 0.01) higher on SSFP images (7.8 +/- 3.7 versus 3.4 +/- 3.3). The CNR between the coronaries and the epicardial fat showed no significant differences (12 +/- 5 versus 13 +/- 4). CONCLUSION: The 3D-navigator SSFP sequence is a promising new technique for MRCA which improves the contrast between the coronaries and the myocardium and shortens the data acquisition compared to gradient-echo imaging.
Subject(s)
Coronary Angiography/instrumentation , Coronary Disease/diagnosis , Image Enhancement/instrumentation , Image Processing, Computer-Assisted/instrumentation , Imaging, Three-Dimensional/instrumentation , Magnetic Resonance Angiography/instrumentation , Adult , Aged , Coronary Vessels/pathology , Female , Humans , Male , Middle Aged , Myocardium/pathology , Reference Values , Sensitivity and SpecificityABSTRACT
Acquired muscular ventricular septal defects (MVSD) after myocardial infarction (MI) can lead to right heart failure and cardiogenic shock with high mortality. Early surgical therapy is often difficult to perform but can reduce the mortality. The closure of congenital septal defects is performed with high safety. Therefore, the interventional closure of an acquired post-MI VSD might be feasible and of potential benefit. To date, experiences with closure of post-MI MVSDs are minimal. We report on two patients with post-MI VSD.
Subject(s)
Cardiac Catheterization , Cardiomyopathies/etiology , Embolization, Therapeutic , Heart Septum , Myocardial Infarction/complications , Aged , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/methods , Equipment Design , Female , Humans , Prostheses and ImplantsABSTRACT
INTRODUCTION: True nodoventricular or nodofascicular pathways and left-sided anterograde decremental accessory pathways (APs) are considered rare findings. METHODS AND RESULTS: Two unusual patients with paroxysmal supraventricular tachycardia were referred for radiofrequency (RF) ablation. Both patients had evidence of dual AV nodal conduction. In case 1, programmed atrial and ventricular stimulation induced regular tachycardia with a narrow QRS complex or episodes of right and left bundle branch block not altering the tachycardia cycle length and long concentric ventriculoatrial (VA) conduction. Ventricular extrastimuli elicited during His-bundle refractoriness resulted in tachycardia termination. During the tachycardia, both the ventricles and the distal right bundle were not part of the reentrant circuit. These findings were consistent with a concealed nodofascicular pathway. RF ablation in the right atrial mid-septal region with the earliest atrial activation preceded by a possible AP potential resulted in tachycardia termination and elimination of VA conduction. In case 2, antidromic reciprocating tachycardia of a right bundle branch block pattern was considered to involve an anterograde left posteroseptal atriofascicular pathway. For this pathway, decremental conduction properties as typically observed for right atriofascicular pathways could be demonstrated. During atrial stimulation and tachycardia, a discrete AP potential was recorded at the atrial and ventricular insertion sites and along the AP. Mechanical conduction block of the AP was reproducibly induced at the annular level and at the distal insertion site. Successful RF ablation was performed at the mitral annulus. CONCLUSION: This report describes two unusual cases consistent with concealed nodofascicular and left anterograde atriofascicular pathways, which were ablated successfully without impairing normal AV conduction system.
Subject(s)
Catheter Ablation , Heart Conduction System/physiopathology , Heart Conduction System/surgery , Tachycardia, Supraventricular/physiopathology , Tachycardia, Supraventricular/surgery , Adult , Atrioventricular Node/physiopathology , Bundle-Branch Block/physiopathology , Cardiac Pacing, Artificial , Electrocardiography , Electrophysiology , Female , HumansABSTRACT
AIM: Most atrioventricular accessory pathways (AV-APs) exhibit Kent bundle physiology characterized by fast and non-decremental conduction properties. In contrast, atriofascicular APs, which are only capable of reaching slow levels of long antegrade decremental conduction, are uncommon. The aim of this study was to describe antegrade and/or retrograde AV-APs with unusual decremental properties. METHODS AND RESULTS: Five patients with unusual decremental AV-APs underwent electrophysiological evaluation and radiofrequency catheter ablation for symptomatic tachycardias. Three were found to have structural heart disease, and three latent decremental AV-APs in the anterograde and/or retrograde direction that could not be demonstrated by routine electrophysiological testing. In Case 1, a right posteroseptal AV-AP with bidirectionally latent decremental conduction was associated with clinical antidromic circus movement tachycardia (CMT) mimicking ventricular tachycardia and orthodromic CMT, the latter inducible only with isoprenaline. In Case 2, incessant orthodromic CMT was due to a latent retrograde left posterolateral AV-AP. In both cases, double atrial responses to a single paced ventricular beat, initiating orthodromic CMT, were observed. In Case 3 with latent preexcitation unmasked by adenosine and atrial pacing, retrograde latent decremental conduction over a right posteroseptal AV-AP could be shown only with isoprenaline. This patient and the remaining two with overt preexcitation demonstrated anterograde decremental AP conduction that was discontinuous over a right posteroseptal AV-AP in Cases 3 and 4 and was continuous over a midseptal AV-AP in Case 5. In the latter case, the site of decremental conduction could be localized at the proximal AP origin. All five AV-APs were successfully ablated at the annulus level. CONCLUSION: AV-APs with unusual decremental properties that are either latent, demonstrable only during CMT or overt, exhibiting functional longitudinal dissociation are described. These APs could be identified and successfully ablated after detailed electrophysiological analysis.
Subject(s)
Arrhythmias, Cardiac/physiopathology , Bundle of His/physiopathology , Electrocardiography/methods , Adenosine/therapeutic use , Adult , Aged , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/therapy , Bundle of His/surgery , Cardiac Pacing, Artificial , Catheter Ablation , Female , Heart Rate , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: We present the case of a 17-year-old woman who underwent an electrophysiological study and radiofrequency (RF) ablation of supraventricular tachycardia refractory to medical treatment. Two right-sided, concealed, nondecremental atrioventricular accessory pathways (AV-APs) involved in orthodromic circus movement tachycardias were identified. After RF ablation of both AV-APs, evidence of bidirectional dual AV nodal conduction was demonstrated and regular narrow complex tachycardia was induced. METHODS AND RESULTS: During the tachycardia, retrograde slow and fast AV nodal pathway conduction with second-degree ventriculoatrial (VA) block and VA dissociation were observed. During the tachycardia with second-degree VA block, ventricular extrastimuli elicited during His-bundle refractoriness advanced the next His potential or terminated the tachycardia. Mapping the right atrial mid-septal region, a distinct high-frequency activation P potential was recorded in a discrete area, two thirds of the way from the His bundle toward the os of the coronary sinus. Detailed electrophysiologic testing with the recordable P potential demonstrated that the tachycardia utilized a concealed nodoventricular AP arising from the proximal slow AV nodal pathway. CONCLUSION: The tachycardia with slow 1:1 VA conduction could be reset by ventricular extrastimuli elicited during His-bundle refractoriness advancing the subsequent activation P potential and atrial activation. RF ablation guided by recording of the activation P potential resulted in elimination of both the slow AV nodal pathway and the nodoventricular connection with preservation of the normal AV conduction system.
Subject(s)
Bundle of His/surgery , Catheter Ablation , Tachycardia, Supraventricular/surgery , Wolff-Parkinson-White Syndrome/surgery , Adolescent , Bundle of His/physiopathology , Electrocardiography , Female , Humans , Tachycardia, Supraventricular/complications , Tachycardia, Supraventricular/physiopathology , Wolff-Parkinson-White Syndrome/complications , Wolff-Parkinson-White Syndrome/physiopathologyABSTRACT
Heparin-induced thrombocytopenia type II (HIT type II) is the most serious complication of heparin treatment apart from bleeding, which is the most common side effect. Eleven days after coronary bypass grafting, a 71 year old patient showed a posterolateral myocardial infarction and a thrombocytopenia of 80,000/microliter. This was considered a postoperative thrombocytopenia. Coronary angiography revealed closed venous bypass grafts. The right coronary artery (RCA) was revascularized by percutaneous transluminal coronary angioplasty (PTCA) and stent placement. During both coronary angiography and PTCA, heparin was administered to the patient. The platelet number did not change. Four days later the patient showed an inferior myocardial infarction and an AV-block III degrees and a syncope. The following coronary angiography revealed RCA stent occlusion. HIT type II was presumed and recanalization was carried out using Lepirudin (Refludan) as the anticoagulant. After placing the guide wire, thrombi could be seen in the proximal RCA. Abciximab (Reo pro), a monoclonal antibody against the glycoprotein IIb/IIIa receptor was additionally administered. Coronary angiography on the next day revealed only a small remaining thrombus. The AV-block disappeared immediately after revascularization. The diagnosis of HIT type II was confirmed through heparin-induced-platelet-activation-test (Hipa-test) and immunoassay (PF 4/heparin-ELISA). This case report illustrates the complicated diagnosis of HIT type II and the successful simultaneous use of Lepirudin (Refludan) and Abciximab (Reo pro). The number of platelets should be checked daily during heparin treatment. In the case of a thrombocytopenia, the treatment should be stopped immediately, and Hipa-test and PF 4/heparin-ELISA should be carried out.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Coronary Artery Bypass/adverse effects , Heparin/adverse effects , Hirudins/analogs & derivatives , Immunoglobulin Fab Fragments/therapeutic use , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy , Abciximab , Aged , Angioplasty, Balloon, Coronary/methods , Heparin/pharmacology , Heparin/therapeutic use , Hirudin Therapy , Humans , Male , Myocardial Infarction/chemically induced , Myocardial Infarction/diagnosis , Myocardial Infarction/drug therapy , Postoperative Complications/drug therapy , Recombinant Proteins/therapeutic use , Stents/adverse effects , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , Thrombosis/diagnosis , Thrombosis/drug therapyABSTRACT
Early action of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI) has been shown in large scale clinical trials to reduce mortality over the first weeks. However, the mechanisms involved are yet unclear and several trials showed a tendency toward a small, albeit unexpected, rise in cardiogenic shock or mortality. Since cardiopulmonary exercise testing (CPX) has become a "gold standard" in assessing the severity of heart failure, we studied--after finishing a pilot trial--the effect of captopril versus placebo in 208 patients who were individually titrated (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve their blood pressure in the acute phase of myocardial infarction; we followed the development of congestive heart failure (CHF) over 4 weeks by measuring oxygen consumption. After 4 weeks, overall oxygen consumption at the anaerobic threshold (VO2-AT; 13.7 vs 13.1), maximal oxygen consumption (VO2max 19.3 vs 18.9 mL/kg per min) and exercise duration (896 vs 839 sec) showed a nonsignificant difference in favor of the captopril group. The predefined, categorized, combined endpoint of severe heart failure or death (heart failure necessitating ACE inhibition, VO2max < 10 mL/kg per min, or death) was significantly reduced in the captopril group (n = 7/104) versus placebo (n = 18/104; p = 0.03). Differences were mainly caused by fewer CHF events (delta n = 10). We conclude that ACE inhibition with individualized dose titration markedly reduces the 4-week incidence of severe heart failure or death; > 10 patients per 100 treated gained major benefits from this therapy.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Captopril/pharmacology , Cardiomegaly/prevention & control , Exercise Test , Heart Failure/prevention & control , Myocardial Infarction/complications , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Blood Pressure/drug effects , Captopril/therapeutic use , Carbon Dioxide/metabolism , Cardiomegaly/diagnostic imaging , Cardiomegaly/etiology , Double-Blind Method , Echocardiography , Female , Germany , Heart Failure/etiology , Heart Ventricles/drug effects , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Oxygen Consumption/drug effects , Treatment OutcomeABSTRACT
1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has been provided that in the perfused hearts and isolated atria PD 81,723 causes a sensitization to adenosine via this mechanism. 2. We have studied the effect of PD 81,723 in guinea-pig isolated atrial myocytes by use of whole-cell measurement of the muscarinic K+ current (I[K(ACh)]) activated by different Gi-coupled receptors (A1, M2, sphingolipid). PD 81,273 caused inhibition of I[K(ACh)] (IC50 approximately 5 microM) activated by either of the three receptors. Receptor-independent I[K(ACh)] in cells loaded with GTP-gamma-S and background I[K(ACh)], which contributes to the resting conductance of atrial myocytes, were equally sensitive to PD 81,723. At no combination of concentrations of adenosine and PD 81,723 could an enhancing effect be detected. 3. The compound was active from the outside only. Loading of the cells with PD 81,723 (50 microM) via the patch pipette did not affect either I[K(ACh)] or its sensitivity to adenosine. We suggest that PD 81,723 acts as an inhibitor of inward rectifying K+ channels; this is supported by the finding that ventricular I(K1), which shares a large degree of homology with the proteins (GIRK1/GIRK4) forming I[K(ACh)] but is not G protein-gated, was also blocked by this compound. 4. It is concluded that the functional effects of PD 81,723 described in the literature are not mediated by the A1 adenosine receptor-Gi-I[K(ACh)] pathway.