Role of the laboratory in monitoring patients receiving dual antiplatelet therapy.

INTRODUCTION: The increasing demand for therapeutic monitoring in patients receiving antiplatelet therapy has been paralleled by the development of instruments and tests whose clinical usefulness is still under debate. We devised a laboratory approach to detect patients with antiplatelet resistance at risk to develop thrombotic events. METHODS: One hundred and eighty patients, under aspirin and clopidogrel after angioplasty and stent implantation, were studied by PFA100(®) with collagen/epinephrine (CoEPI, cutoff 165s) cartridge and by Multiplate(®) using arachidonic acid (ASPItest, pos < 862AUC), ADP (ADPtest, pos < 417AUC), and collagen (COLtest, pos < 607AUC). RESULTS: Only 67 of 173 patients with ASPI < 862 displayed a prolonged CoEPI and up to 65 patients had normal CoEPI despite ASPI < 300. Patients with ASPI < 300 had significantly lower COL than patients with ASPI > 300. One hundred and thirty-eight patients displaying ADP < 417 had significantly lower COL than those with ADP > 417. Association between COL and ADP remained after ASPI stratification: in patients with suboptimal (ASPI 300-892) or maximal (ASPI < 300) response to aspirin, having ADP < 417 (clopidogrel responsive) increased COL positivity, respectively, from 9.5 to 58.8% and from 47.6 to 82.7%. CONCLUSION: A combination of specific tests may be useful in identifying higher-risk patients with poor compliance or drug resistance who potentially may benefit from therapy change.

Toxoplasmose: ocorrência de anticorpos antitoxoplasma gondii e diagnóstico / Toxoplasmosis: occurrence of antibodies antitoxoplama gondii and diagnosis

A toxoplasmose é uma zoonose de ampla distribuiçäo geográfica, sendo uma infecçäo oportunista, principalmente em pacientes com Aids. A incidência dos anticorpos séricos, antiToxoplasma gondii, é variável, sendo crescente com os diferentes grupos etários. Os métodos laboratoriais para o diagnóstico desta doença incluem o exame da espécie patógena e os testes imunológicos. Embora os testes sorológicos tenham suas limitações, säo ainda os mais utilizados nos laboratórios de análises clínicas. Na melhoria do diagnóstico da toxoplasmose congênita e em pacientes com AIDS, tem-se empregado, alternativamente, a reaçäo em cadeia de polimerase (PCR) e Nested-PCR. OBJETIVOS: Enfocar a ocorrência de toxoplasmose, considerando-se as diferentes técnicas e formas de interpretaçäo nos exames sorológicos. MÉTODOS: No presente trabalho, avaliamos os anticorpos (Ac) antiToxoplasma gondii de 2.994 pacientes atendidos no Laboratório do Hospital Universitário (LAC-HU), da Universidade Federal de Santa Catarina, no período de 28 de fevereiro de 1996 a 28 de julho de 1998. Essa avaliaçäo foi realizada através da utilizaçäo da reaçäo de Imunofluorescência Indireta (IFI) e confirmada pelo método do ensaio imunoenzimático (ELISA). RESULTADOS: Os resultados mostraram que 41,91 por cento desses pacientes possuíam Ac antiToxoplasma gondii, sendo que 0,87 por cento possuíam IgM, em diferentes títulos, estando ou näo desenvolvendo a fase aguda da doença. Este estudo vem demonstrar que a prevalência de toxoplasmose em nosso meio é relativamente alta e que para a identificaçäo do processo agudo da doença, a rotina sorológica pode ser enriquecida de técnicas mais sensíveis e específicas, que permitam a evidenciaçäo do microrganismo, contribuindo para o melhor diagnóstico

[Toxoplasmosis: occurrence of antibodies antitoxoplasma gondii and diagnosis]. / Toxoplasmose: ocorrência de anticorpos antitoxoplasma gondii e diagnóstico.

UNLABELLED: Toxoplasmosis is a zoonosis of broad geographic distribution, being an opportunist infection mainly in AIDS patients. The incidence of serum antibodies of the type anti-Toxoplasma gondii is variable and growing according the different age groups. The laboratory test for the diagnostic of this disease, include the exam of the pathologic species as well as immunologic tests. Although the serum tests have limitations, they are still utilized in the Clinical Analysis laboratories. To improve the congenital toxoplasmosis diagnosis in AIDS patients, the polymerase chain reaction (PCR) and Nested-PCR have been utilized alternatively. PURPOSES: To focus the occurrence of toxoplasmosis, considering the different techniques and shapes of point of views in the serological analysis. METHODS: The antibodies (Ac) anti-Toxoplasma gondii of 2994 patients from the Santa Catarina Federal University Hospital, in the period from February 28, 1996 to July 28, 1998 were evaluated. This evaluation was accomplished by the Immunofluorescency Indirect reaction, which was confirmed by the ELISA method. RESULTS: The results showed that 41.91% of the patients had the antibodies anti-Toxoplasma gondii. From this total we concluded that 0.87% of these patients had the IgM in different titles which can be or not classified in the acute phase of the disease. This study demonstrates that the incidence of toxoplasmosis in our orment is relatively high. It shows too that in the identification of the acute process of the disease, the serologic tests can be added to a more sensible and specific techniques that allows the evidentiation of the microorganism thus contributing to a better diagnosis.

Prognostic value of the admission electrocardiogram in acute coronary syndromes.

CONTEXT: The presence of ischemic changes on electrocardiogram (ECG) correlates with poorer outcomes in patients with acute chest pain. OBJECTIVE: To determine the prognostic value of various ECG presentations of acute myocardial ischemia. DESIGN: Retrospective analysis of the presenting ECGs of patients enrolled in Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb). SETTING: Three hundred seventy-three hospitals in 13 countries in North America, Europe, Australia, and New Zealand. PATIENTS: A total of 12142 patients who reported symptoms of cardiac ischemia at rest within 12 hours of admission and had signs of myocardial ischemia confirmed by ECG. On presenting ECG, 22% of patients had T-wave inversion, 28% had ST-segment elevation, 35% had ST-segment depression, and 15% had a combination of ST-segment elevation and depression. MAIN OUTCOME MEASURE: Ability of presenting ECG to predict death or myocardial reinfarction during the first 30 days of follow-up. RESULTS: The 30-day incidence of death or myocardial reinfarction was 5.5% in patients with T-wave inversion, 9.4% in those with ST-segment elevation, 10.5% in those with ST-segment depression, and 12.4% in those with ST-segment elevation and depression (P<.001). After adjusting for factors associated with an increased risk of 30-day death or reinfarction, compared with those who had T-wave inversion only, the odds of 30-day death or reinfarction were 1.68 (95% confidence interval [CI], 1.36-2.08) in those with ST-segment elevation, 1.62 (95% CI, 1.32-1.98) for those with ST-segment depression, and 2.27 (95% CI, 1.80-2.86) for those with combined elevation and depression. An elevated creatine kinase level at admission correlated with a higher risk of death (odds ratio [OR], 2.36; 95% CI, 1.92-2.91) and death or reinfarction (OR, 1.56; 95% CI, 1.32-1.85). The ECG category and creatine kinase level at admission remained highly predictive of death and myocardial infarction after multivariate adjustment for the significant baseline predictors of events. CONCLUSIONS: The ECG at presentation allows immediate risk stratification across the spectrum of acute coronary syndromes. An elevated creatine kinase level at admission is associated with worse outcomes.

[Short and intermediate term clinical outcome in patients with cardiogenic shock treated with aortic counterpulsation]. / Evoluzione clinica a breve e medio termine di pazienti cardiopatici in shock cardiogeno trattati con contropulsazione aortica.

BACKGROUND: Despite improvements in coronary care, cardiogenic shock (CS) remains the leading cause of death in patients with dramatic cardiac diseases of which acute myocardial infarction (AMI) is the most frequent event. Conventional therapy for CS with coronary care unit (CCU) monitoring and vasopressor agents to support blood pressure has historically been associated with an 80% to 90% mortality rate in large series. Intra-aortic balloon pump (IABP) therapy for shock results in initial favourable clinical and haemodynamic responses, but ultimately, in most patients, death is merely delayed and hospital mortality still exceeds 80%. In several recent non-randomised series, coronary revascularisation performed early in the course of CS with the use of coronary artery by-pass grafting (CABG) or coronary angioplasty (PTCA) resulted in an apparent reduction in the hospital mortality rate to less than 50% in selected patients with shock. OBJECTIVES: This study reviews our experience of cardiogenic shock treatment at a time when standard care included aggressive use of the intra-aortic balloon pump counterpulsation, cardiac catheterisation, coronary angioplasty and/or coronary artery by-pass grafting, ventricular septal defect and mitral incompetence repair. METHODS: We retrospectively analysed 20 patients (13 M and 7 F, with an average age of 62 years and a half) affected by cardiogenic shock consecutively admitted to our CCU between October 1, 1992 and April 1, 1995. Fifteen patients (pts) were hospitalised for AMI, shock and pump failure (2 of them with pulmonary oedema), all with admittance delay less than 24 hours. Five patients were hospitalised for AMI with shock and mechanical defects, of which 3 pts with AMI and ventricular septal rupture and 2 pts with AMI and mitral regurgitation. All patients underwent IABP, coronary angiography (CA) and then were treated with PTCA, CABG and cardiac surgery or medical treatment. RESULTS: On the whole, 7 pts died (35%): 4 of shock, 1 of haemorrhagic complications, 1 of septic shock in the CCU, and 1 of heart failure after CABG in cardiosurgery. One more patient died of heart failure two months after discharge (late mortality 5%). Out of the 15 patients hospitalised with AMI, shock and pump failure, 13 patients with AMI and CS less than 24 hrs were treated as follows: 1 patient was successfully submitted to emergency CABG and 12 patients to PTCA of the infarct related artery (IRA). Eight patients enjoyed a good outcome, but 1 patient died of haemorrhagic complications and 4 with a persistently occluded IRA also died (3 in the CCU and 1 after CABG). Of the 2 remaining pts with AMI, shock and pulmonary oedema, 1 patient underwent CABG with success and 1 patient with the 3-vessel disease was submitted to PTCA with reperfusion of the IRA, but he died from reocclusion three days later. Out of the 5 patients with AMI, shock and mechanical defects, 3 patients with AMI and septal ventricular rupture underwent cardiac surgery and CABG with early and late success. One of the 2 patients with AMI, shock and mitral regurgitation underwent cardiac surgery with valve repair and CABG and had a good outcome, the other died from septic complications in the CCU. CONCLUSIONS: IABP is an useful device for stabilising patients in cardiogenic shock and safely performing angiography as well as PTCA, CABG or surgical correction of all mechanical complications with a more stable haemodynamic balance. Therefore, IABP is an useful tool to improve successful coronary revascularisation after direct PTCA or direct CABG. These data also suggest that the combination of successful coronary revascularisation and intra-aortic balloon pumping can improve survival in pts with cardiogenic shock complicating AMI with early pump failure.

Silent versus symptomatic dipyridamole-induced ischemia after myocardial infarction: clinical and prognostic significance.

The prevalence and prognostic significance of silent myocardial ischemia were prospectively assessed in 217 patients (mean age 57 +/- 9 years, 83% male) recovering from a first uncomplicated acute myocardial infarction and undergoing a dipyridamole echocardiography test before hospital discharge. Clinical, angiographic, exercise electrocardiographic (ECG) and dipyridamole echocardiographic variables were also examined. Of the 217 patients, 89 had no echocardiographically proved dyssynergy after dipyridamole, whereas 128 had dipyridamole-induced wall motion abnormalities that were silent in 94 (Group I) and symptomatic in 34 (Group II). There was no intergroup difference with respect to dipyridamole time (i.e., the time from onset of the test to frank dyssynergy: 7 +/- 3 vs. 8 +/- 3 min; p = NS); prevalence of inferior myocardial infarction (69% vs. 71%; p = NS); ischemic ECG changes during the test (83% vs. 71%; p = NS); diabetes (8.5% vs. 6%; p = NS); ongoing medical therapy; multivessel disease (57% vs. 56%; p = NS); and baseline left ventricular ejection fraction (57 +/- 13% vs. 57 +/- 10%; p = NS). There was also no significant difference between Group I and Group II with respect to wall motion score index at peak dipyridamole effect (1.77 +/- 0.39 vs. 1.78 +/- 0.36; p = NS). Patients were followed up for 24 +/- 4 and 25 +/- 5 months, respectively (p = NS). Life table analysis revealed no difference in unstable angina, reinfarction and death between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological sensitivity of respiratory-dependent cardiac pacing: four-year follow-up.

Clinical and physiological data on long-term follow-up of 143 patients with respiratory-dependent pacemakers (RDP3) are reported; 121 patients received ventricular (VVI-RD) and 22 patients atrial (AAI-RD) respiratory-dependent stimulation. Functional evaluation was based on the exercise testing (130 pts) with oxygen uptake VO2, ventilation, ECG and arterial pressure monitoring and the dynamic Holter electrocardiogram (95 pts). In each patient, the stimulation rate curve selected was that which produced the best work tolerance and moved the anaerobic threshold to the right. Respiratory levels were assessed by telemetry verifying proper sensing of tidal volume variations and absence of interference and artefacts. In patients with VVIR or AAIR stimulation, exercise tolerance, oxygen uptake and anaerobic threshold increased significantly in comparison with VVI or AAI pacing respectively. The physiological sensitivity of the stimulation system (i.e., a linear relationship of the pacing rate with metabolic requirements) was excellent (up to exhaustion) in 70%, very good (up to anaerobic threshold) in 20% and erratic (no relationship between pacing rate and VE/VO2) in 10% of patients. In dynamic electrocardiographic monitoring, the automatic pacing rate was always predominant during the night and during rest periods; the pacing rate increased properly with daily activity; myopotential inhibition (none longer than 3,500 ms) was observed in 38 patients, but without subjective complaints. The incidence of the RDP3 malfunction was less than 8%; it may have stemmed from the pacing system itself, or from other clinical conditions. Oversensing of impedance system pulses has not been recorded in the last 3 years. Partial respiration undersensing results from incorrect accessory lead position, pulmonary emphysema, marked obesity or other causes. Respiratory sensing becomes erratic at the anaerobic threshold point in such patients, but functions well at submaximum exercise levels. In patients with left ventricular failure, exercise tolerance was improved by setting a lower ratio between the pacing rate and respiration, which prevented the occurrence of excessive pacing rates.

[Physiologic limitations of dual chamber stimulators during physical activity]. / Limitazioni fisiologiche degli stimolatori bicamerali durante l'attività fisica.

Dual chamber DDD pacing is fully physiologic when chronotropic response of sinus node to exercise is normal and when retrograde ventriculo-atrial conduction is absent. Comparison of results from exercise test with increasing work load showed that atrial-triggered ventricular pacing provides a significant functional benefit (delta VO2 15%) P less than 0.01, if compared with fixed rate ventricular pacing. The benefit is closely related with the amount of sinus rate increase during exercise. In patients with sinus node syndrome the atrial triggered ventricular pacing rate did not show significant increase during exercise and exercise capability was similar to that observed with fixed ventricular pacing. Retrograde ventriculo-atrial conduction was observed in 56% of patients with sick sinus syndrome and 28% of patients with complete AV block and was the reason for endless loop tachycardias (ELTs). ELTs can be eliminated by lengthening atrial refractory period (ARP). In patients with ARP greater than or equal to 250 ms (47%), mild (8:7, 4:3) or important (2:1) AV block appeared during exercise test, with sudden drop of pacing rate and cardiac output at highest work load. Among other "physiologic" pacing modes, respiration traced ventricular stimulation showed high physiologic sensitivity (90%) and haemodynamic benefit comparable to that obtained during dual chamber pacing and without the related disadvantages.

[Arrhythmia in patients with a DDD bicameral pacemaker]. / Aritmie in pazienti portatori di pacemaker bicamerale DDD.

Dual chamber pacemakers, with coordinate atrial and ventricular sensing and stimulation (DDD), even if allowing "physiological" pacing, exhibited new and complicated arrhythmic manifestations, whose real frequency is still unascertained. In 65 patients (mean age 68 +/- 12 years), implanted with a DDD multiprogrammable device (15 pts. Medtronic Versatrax 7000 A, 50 pts. Pacesetter AFP 283), we carried out a 24 hours Holter monitoring while pacemaker was programmed with standard parameters. In a subset of 15 patients Holter monitoring was performed before and after pacemaker implantation. We evidenced: a) atrial sensing and/or pacing malfunction in 3 patients (4.5%); b) pacer-unrelated arrhythmias in 49 patients (75%): atrial extra beats 35 patients (54%), ventricular extra beats 23 patients (35%), non-sustained ventricular tachycardias 10 patients (15%), atrial tachyarrhythmias 8 patients (12%); c) supraventricular arrhythmias with PM-mediated high rate ventricular pacing in 12 patients (18%); d) PM induced and sustained endless loop tachycardias in 31 patients (47%); e) arrhythmias depending on over-sensing in 11 patients (17%): myopotential interferences 9 patients (14%), cross-talk ventricular pacing inhibition 2 patients (3%). The prevalence of ventricular arrhythmias was not different before and after the pacemaker implantation. The prevalence of atrial extrasystoles (53% versus 40%) and atrial tachyarrhythmias (26% versus 6%) decreased after the pacemaker implantation. Aimed reprogramming with progressive extension of atrial refractory period (from 250 to 400 msec and DDX) achieved disappearance of PM-endless loop tachycardias in 95%. Use of multi-programmability lowered the incidence and symptoms of most PM-related arrhythmias. Drug therapy was of choice in clinical arrhythmias unrelated to pacer.

[Ventricular repolarization abnormalities and arrhythmia in the athlete. A long-term follow-up clinical case]. / Anomalie della ripolarizzazione ventricolare e aritmie nell'atleta. Caso clinico di osservazione prolungata.

Clinical and prognostic significance of ventricular repolarization anomalies in sportsmen is still uncertain, even if they are most commonly regarded as benign. We studied a patient in whom those manifestations didn't show any progression within 30 years even after interruption of athletics and were related to idiopathic hypertrophic cardiomyopathy. Anatomical findings were combined with cardiac rhythm and conduction disturbances (paroxysmal atrial flutter, premature contractions, 2nd degree AV block). In our patient ventricular repolarization anomalies, even though without a negative prognosis, can't be related to "athlete's heart" but rather to organic cardiomyopathy.

[Late potentials, myocardial kinetics and ventricular vulnerability as markers of sudden death after myocardial infarct]. / Potenziali "tardivi", cinetica miocardica e vulnerabilità ventricolare come "markers" di morte improvvisa dopo infarto miocardico.

The 1st myocardial infarction requires the identification of patients who are at high risk of malignant ventricular arrhythmias. Our study group included 55 consecutive patients (age less than 70): all had non-invasive "signal averaging" recording and 24 hour dynamic electrocardiogram at the post-acute phase of their 1st myocardial infarction (MI) and 3 months later. Wall motion abnormalities were evaluated in each patient but two. 24 randomized patients (without documented sustained ventricular tachycardia) underwent right programmed ventricular stimulation at the 3rd month after MI and pathological repetitive responses were evaluated (Table III); they were hemodynamically stable and without persistent ischemia. Late potentials have been compared to spontaneous and induced ventricular arrhythmias, wall motion abnormalities (Table II) and two-year follow-up (Table VI), in order to identify predictive markers of sudden death or malignant arrhythmias. Ventricular late potentials were identified in 28 patients (51%) 4-8 days after MI: mean duration was equal to 75 +/- 33 msec; they did not show any relationship to the site (Table I) and to the extension of necrosis (Table II). Ventricular late potentials had no significant association with myocardial dyskinesia (Table II) while their association with complex ventricular arrhythmias, detected on Holter monitoring within 8 days after MI, and with the induction of repetitive ventricular responses (greater than or equal to 2 complexes) showed significant correlations (respectively p = 0.02; p = 0.01). In regard of the recognition of spontaneous ventricular tachycardia (greater than or equal to 3 complexes) in the follow-up, the detection of late potentials showed 75% sensibility with predictive value equal to 32% (Table V); the combination of late potentials and ventricular dyskinesia exhibited the highest specificity (88%) and predictive value (54%). By the end of follow-up there had been 6 cardiac deaths (2 sudden, 4 from left ventricular failure): late potentials longer than 75 msec were recorded in all patients who had cardiac death; in the post acute phase of MI repetitive ventricular arrhythmias were detected in only 1 of the 2 case of sudden cardiac death and in none of the patients who developed sustained ventricular tachycardia in the follow-up (Table VI). Myocardial dyskinesia was present in each patient who developed non sudden cardiac death (Table VI).(ABSTRACT TRUNCATED AT 400 WORDS)

Respiration-dependent ventricular pacing compared with fixed ventricular and atrial-ventricular synchronous pacing: aerobic and hemodynamic variables.

A pacemaker that adapts heart rate in response to the patient's metabolic requirements has been developed. The pacemaker uses breathing frequency and tidal volume as the indicators of physiologic demand. Maximal physical work capacity, anaerobic threshold, oxygen uptake (16 patients) and hemodynamic variables (9 patients) were assessed with fixed rate (VVI), atrial synchronous (VDT/I) and respiration-dependent ventricular (VVI-RD) pacing. All subjects attained their anaerobic threshold in stress tests with VVI pacing. The maximal physical capacity (p less than 0.001), work time to attain the anaerobic threshold (p less than 0.01) and oxygen uptake (p less than 0.001) were significantly greater with VVI-RD than with VVI pacing. The transition from the supine to the standing position was characterized by a significant increase of cardiac index at rest with both VDT/I and VVI-RD pacing as compared with VVI pacing. Progressive increments in the cardiac index and average left ventricular stroke work index were significantly different at submaximal and maximal exercise when VVI and VVI-RD were compared. At maximal exercise, mean cardiac output was also significantly different: 10.21 +/- 2.5 (SD) liters/min with VVI, 11.2 +/- 0.8 liters/min with VDT/I (p less than 0.05) and 12.65 +/- 3.1 liters/min with VVI-RD (p less than 0.05) pacing. Maximal oxygen extraction values were greater with VVI and VVI-RD pacing than with VDT/I pacing. Pulmonary artery end-diastolic pressures at maximal exercise were within the normal range with the three different modes of pacing. In conclusion, there is a significant (25%) improvement in exercise performance with VVI-RD pacing as compared with VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Increasing cardiac rate by tracking the respiratory rate.

The rate responsive pacemaker using respiratory rate as a sensor was implanted in 22 patients, 19 patients for ventricular pacing and three for atrial pacing. The level of exercise achieved with this system was consistently higher than with a fixed ventricular pacing rate. In addition, no special chemical or mechanical sensors are required; the sensor itself is simple, long-lasting, and energy efficient. Thus, this system adapts easily to the individual patient.

[Non-invasive recording of the His bundle electrogram: choice of leads and reliability of the "averaging" technic]. / Riconoscimento non invasivo dell'elettrogramma hisiano: scelta delle derivazioni e attendibilità della tecnica di "averaging".

An improvement in detecting His bundle activity using a Marquette high resolution Mac unit, without pharmacologic depression of AV node conduction, was obtained with two surface lead systems, which were selected on the basis of the His bundle anatomical position and its electrostimulation axis. In 8 patients the direction of the His bundle bipolar stimulation vector was evaluated in the frontal plane, on the orthogonal leads and with map of the chest potential. In 39 patients the surface recording, using high-gain amplification, filtering between 50-300 Hz and an averaging of 256-512 cycles, was obtained by positioning the electrodes in the following sites: manubrium sterni-xiphisternum-V4. When this lead system failed, it was replaced by another one, which included V4-right sternal and right vertebral border at the level of the 3rd intercostal space. In 24 patients (PR less than 0.16" in 4 cases) intracavitary and surface H-V recording were compared. The surface interval was measured between the apex of the surface "blip" and onset of the QRS. Sensitivity was 86% with a good correlation (r = 0.94) between invasive and non-invasive measurements. The surface leads, in which the His bundle activity was best detected, were the manubrium-xiphisternum (on the midsternal line) and V4-right vertebral border at the 3rd intercostal space level. Our external measurement technique avoids subjective misinterpretations; the surface H-V interval was on an average 6 msec. shorter than the invasive one. The upper normal value of non-invasive H-V interval is therefore 50 msec in our measurement method.