MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects.

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).

The MCP-1 -2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population.

We investigated the MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) in Slovak cohort of patients with ischemic heart disease (IHD). Our study comprised 270 patients with IHD, out of them 92 with myocardial infarction (MI). We found that the frequencies of the mutant GG genotype in Slovak patients with IHD (10.7%; p=0.019) and MI (12.0%; p=0.046) were significantly higher than those in the control subjects (5.8%). After subdividing the groups according to the sex, statistically significant difference was found only in men (IHD: p=0.013, MI: p=0.009). We also found a higher rate of GG homozygous genotype in patients with early (< or =50 years of age) MI (18.4%; p=0.004)--statistically significant again only in men (23.1%; p=0.002). The frequencies of G alleles in IHD male patients (30.3%, p=0.046) and in early MI male patients (38.5%, p=0.019) were also statistically significantly higher than in control group. Our results confirm that IHD and MI are linked to MCP-1 -2518 (A/G) single nucleotide polymorphism (Tab. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.

Science and religion.

Religion and science have often been in conflict throughout human history. There are many who think that they can never be reconciled. In this essay, it will be argued that religion and science are in harmony, and, in fact, they are both necessary for the advancement of human civilization. In essence, religion and sciences represent to pathways in the search for truth. In general, religion deals with spiritual matters and science with physical matters. In some cases they overlap. The very word, "science" has had different meanings throughout the centuries. The sciences studied in the ancient world, such as alchemy, would have no meeting today. It is likely that some sciences, which are considered very important today, will in future centuries become irrelevant. (Ref. 15.).

Acute hemodynamic effects of alternate and combined site pacing in patients after cardiac surgery.

We hypothesized that pacing at sites other than the right ventricular (RV) apex or at two or more ventricular sites would activate the myocardium more rapidly and improve cardiac function in patients undergoing coronary revascularization or aortic valve replacement. Epicardial electrodes were placed on the right atrium (A), RV paraseptal area close to the RV apex (B), RV outflow tract (C), LV apex (D), in patients undergoing bypass surgery. At constant rate and AV delay, we measured CO during A pacing, DVI pacing at B, C, D, and various combinations of sites in random order in ten patients with EF > 50% and 27 patients with EF < or = 50%. When pacing at two sites, we made one electrode a cathode and one an anode and noted two distinct thresholds by careful observation of the 12-lead ECG. There were no significant differences in CO, systemic vascular resistance, systolic, or mean arterial pressure. Significant differences were noted in QRS duration, which increased progressively going from AAI to 3-site, 2-site, and single site pacing (P < 0.05 each comparison). Thus: (1) QRS duration correlated inversely with the number of ventricular sites paced; (2) despite this, CO did not improve irrespective of baseline EF; (3) multisite pacing produced multiple distinct thresholds which appeared to be related to the number of sites paced, and (4) unique ECG patterns confirmed multisite pacing.

Systolic and diastolic function with alternate and combined site pacing in the right ventricle.

UNLABELLED: We hypothesized that pacing at two ventricular sites simultaneously would activate the myocardium more rapidly and improve ventricular function. We studied the effect of pacing at the right ventricular outflow tract (RVOT) and the RV apex (RVA) on systolic and diastolic function. In 14 patients with a reduced systolic ejection fraction < 40% (mean EF 32% +/- 4%) we measured RV pressures, left ventricular pressures, EF, cardiac output, peak dP/dt, peak negative dP/dt, and the time constant of relaxation, Tau, during intrinsic rhythm, atrial pacing and DVI pacing at the RVA, the RVOT, and both RV sites combined in random order. Repeated measures analysis of variance showed no significant differences in any of these parameters. The highest absolute values of dP/dt were observed during sinus rhythm and the lowest with RVA pacing. This parameter tended to improve progressively with pacing in the RVOT and at both sites. Peak negative dP/dt showed a similar nonsignificant trend. CONCLUSION: These data suggest that in patients with poor LV function, there may be subtle improvements in diastolic and systolic function with pacing in the RVOT and at combined sites in the RV compared to traditional RVA pacing.

Coronary vasomotion after percutaneous transluminal coronary angioplasty depends on the severity of the culprit lesion.

OBJECTIVES: This study sought to evaluate coronary vasomotor response to percutaneous transluminal coronary angioplasty (PTCA) and its influence on proximal and distal vessel diameters with regard to stenosis severity and coronary blood flow. BACKGROUND: Coronary vasoconstriction of the distal vessel segment has been reported after PTCA. This vasoconstrictive effect was thought to be due to balloon-induced injury of the vessel wall, with release of local vasoconstrictors or stimulation of the sympathetic system with release of catecholamines, or both. METHODS: Thirty-nine patients were prospectively studied before and after PTCA. Patients were classified into two groups according to the severity of the culprit lesion: group 1 = > or = 70% to < or = 85% diameter stenosis (n = 23); and group 2 = > 85% to < or = 95% diameter stenosis (n = 16). The coronary vessel diameter of the proximal and distal vessel segments as well as the minimal lumen diameter were determined by quantitative coronary angiography. In a subgroup of 16 patients, basal and maximal coronary flow velocity was measured before and after PTCA with the Doppler FloWire system. RESULTS: The groups were comparable with regard to age, gender, serum cholesterol levels and medical therapy. The proximal vessel segment remained unchanged after PTCA in group 1 ([mean +/- SD] 0.9 +/- 3.5%, p = 0.8) but showed vasodilation in group 2 (+13.7 +/- 3.6%, p < 0.05). However, the distal segment showed vasoconstriction in group 1 (-6.7 +/- 2.0%, p < 0.01) and vasodilation in group 2 (+31 +/- 8.0%, p < 0.01). A significant correlation was found between the change in distal vessel diameter after PTCA and stenosis severity (r = 0.61, p < 0.0001). Changes in blood flow were directly correlated to stenosis severity (r = 0.85, p < 0.002); that is, rest flow increased after PTCA in narrow lesions but remained unchanged in moderate lesions. The diameter changes in the distal vessel segment after PTCA were significantly related to flow changes (r = 0.90, p < 0.0001). Coronary distending pressure of the distal vessel segment increased significantly in both groups; however, this increase was significantly greater in group 2 than in group 1 (55 +/- 4 vs. 14 +/- 3 mm Hg, p < 0.0001). CONCLUSIONS: Coronary vasomotion of the proximal and distal vessel segments after PTCA depends on the severity of the culprit lesion; that is, vasoconstriction of the distal segment is found in patients with moderate lesions and vasodilation in those with severe lesions. Thus, vasomotion of the post-stenotic vessel segment depends on the severity of the culprit lesion and is influenced by changes in coronary flow or distending pressure, or both.

Vibration, acceleration, gravitation, and movement: activity controlled rate adaptive pacing during treadmill exercise testing and daily life activities.

Activity-based sensors for rate adaptive pacing have been available for several years and now include several different types: vibration; acceleration; gravitation; and movement. However, a systematic comparison evaluating the relative advantages and disadvantages of these various sensors has received little study. The purpose of the present study was to compare these sensor subtypes using treadmill testing and an outdoor test circuit, which simulated daily life activities and included both uphill and downhill walking. Pacemakers were strapped on the chest of healthy volunteers and connected to one channel of an ambulatory recording device, which also recorded the subject's intrinsic heart rate. The pacemakers were programmed using an initial treadmill test to standardize the rate responsive parameters for each device. Nine different pacemaker models were studied including 3 vibration-based (Elite, Synchrony, Metros), 4 acceleration-based (Relay, Excel, Ergos, Trilogy), 1 gravitational-based (Swing), and 1 movement-based (Sensorithm) device. All devices demonstrated a prompt rate response with casual walking on flat ground. The vibration-, gravitational-, and movement-based pacemakers showed a pronounced rate decline during more strenuous work, e.g., walking uphill. This phenomenon was absent in the accelerometer-based units. In particular, the vibration- and movement-based units showed a higher rate with walking downhill compared to uphill. An optimally tuned rate behavior on the treadmill usually did not provide an optimal rate behavior during daily activities and there was a tendency to overstimulation during low workload. The development of the two newest sensors (gravitational and movement) did not result in an improved performance of rate response behavior. Overall, the accelerometer-based pacemakers simulated or paralleled sinus rate behavior the most closely.

High thresholds may alter end-of-life behavior in a dual chamber pacemaker.

We noted a series of 12 consecutive patients with a DDD Genisis pacemaker that showed an unexpected and a relatively rapid fall in battery voltage and output as these devices approached end-of-life (EOL). Twenty-one of 24 leads were Vitatron Helifix leads and there was a relatively high mean threshold (atrial 2.5 +/- 0.94 V; ventricular 2.9 +/- 0.65 V). These devices were replaced after 65 +/- 12 months. During the 9.3 +/- 3.5 months before replacement, a striking fall in voltage from 2.7 +/- 0.04 V to 2.49 +/- 0.05 V was seen. Battery impedance rose from 3 +/- 1.2 K omega to 10.2 +/- 4.3 K omega during this same period. We unexpectedly observed a marked difference between programmed and telemetered output for both atrial (50%) and ventricular leads (30%). A discrepancy between measured and telemetered magnet rate was also seen. Despite this relatively rapid fall in battery voltage, several of these devices did not meet the manufacturer's recommended replacement time (RRT) criteria by magnet rate or according to the projected RRT determined by the relationship of battery impedance to current drain. These data have implications for the selection of RRT and EOL criteria for this device. Magnet rate measured by surface ECG was the safest indicator for RRT. Follow-up for this pulse generator should be increased to every 2 months when battery impedance is > 2 KOhms or if there is a difference between programmed and measured output amplitude of more than 15%. The data also highlight the effect of combining high threshold leads with modern pacemakers with relatively "small" batteries as well as certain problems with telemetered data.

Acute hemodynamic effects of atrioventricular pacing at differing sites in the right ventricle individually and simultaneously.

We hypothesized that pacing, which provided a rapid uniform contraction of the ventricles with a narrower QRS, would produce a better stroke volume and cardiac output (CO). We sought to study whether pacing simultaneously at two sites in the right ventricle (right ventricular apex and outflow tract) would provide a narrower QRS and improved CO in 11 patients undergoing elective electrophysiology studies. Patients were studied by transthoracic echocardiography measurement of CO using the Doppler flow velocity method in normal sinus rhythm, AOO pacing (rate 80), DOO pacing in the right ventricular apex (AV delay 100 ms), DOO pacing in the right ventricular outflow tract, and DOO pacing at both right ventricular sites simultaneously in random order. The COs were 5.42 +/- 1.83, 5.61 +/- 1.97, 5.67 +/- 1.6, 5.84 +/- 1.68, and 5.86 +/- 1.52 L/min, respectively (no significant difference by repeated measures analysis of variance [ANOVA]). The QRS durations were 0.09 +/- 0.02, 0.09 +/- 0.02, 0.13 +/- 0.027, 0.13 +/- 0.03, and 0.11 +/- 0.03 secs respectively. Repeated measures ANOVA showed that the QRS duration significantly increased with right ventricular apex or right ventricular outflow tract pacing compared to sinus rhythm and AOO pacing (P < 0.001) but then diminished with pacing at both sites (P < 0.01). QRS duration was not correlated with CO, however the change in QRS duration correlated significantly with the change in CO when pacing was performed at the two right ventricular sites simultaneously. In conclusion, during DOO pacing, there was a trend for pacing in the right ventricular outflow tract or both sites to improve the CO compared to the right ventricular apex. With simultaneous pacing at both ventricular sites, the QRS narrowed. Further studies will be required to see if this approach has value in patients with poor left ventricular function or congestive heart failure.

Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).

BACKGROUND: The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos. METHODS AND RESULTS: CAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency > or = 50/h and heart rate > or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction < or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01). CONCLUSIONS: Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment.

Report of the NASPE Policy Conference on antibradycardia pacemaker follow-up: effectiveness, needs, and resources. North American Society of Pacing and Electrophysiology.

On May 4-5, 1993, a policy conference was held in San Diego, California, under the sponsorship of the North American Society of Pacing and Electrophysiology (NASPE) to identify the fundamental goals of antibradycardia pacemaker follow-up, evaluate the effectiveness with which it achieves those goals, and formulate specific recommendations as to how it can be made more effective. The conference addressed clinical, administrative, and educational objectives, focusing on existing and potential resources for follow-up testing and the appropriate frequency of their application. The training of physicians and associated professionals engaged in follow-up also was addressed, as were regulatory and reimbursement issues. This report summarizes the conclusions and recommendations arrived at during the conference and subsequently approved by the NASPE Board of Trustees.

Differences in corrected QT intervals at minimal and maximal heart rate may identify patients at risk for torsades de pointes during treatment with antiarrhythmic drugs.

The mechanism of torsades de pointes as a proarrhythmic response to antiarrhythmic drugs is not clear. We hypothesized that the difference in the corrected QT interval (QTc, Bazett's formula) with varying autonomic tone and heart rate during 24-hour ambulatory ECG would help identify patients at risk. Ten patients with antiarrhythmic drug-induced torsades de pointes were compared with 28 controls. The QTc at maximal and minimal heart rate during antiarrhythmic drug-free ambulatory ECGs were measured. The mean QTc at minimal heart rates for patients was 0.413 +/- 0.102 seconds and 0.420 +/- 0.072 seconds and for controls (P = 0.715). The mean QTc at maximal heart rates for patients was 0.555 +/- 0.022 seconds and for controls was 0.439 +/- 0.011 seconds (P = 0.001). Mean QTc between minimal and maximal heart rates were significantly different for patients (P = 0.015) but were not for controls (P = 0.151). Using an arbitrary QTc difference cutoff of 0.075 seconds, this approach identified patients at risk for antiarrhythmic drug-induced torsades de pointes with a sensitivity of 70% (7 of 10) and a specificity of 89% (P < or = 0.003 by Chi-square analysis with Yates' correction). In conclusion, patients with antiarrhythmic drug-induced torsades de pointes had a greater rise in QTc from minimal to maximal heart rate during ambulatory ECG than controls. Further larger prospective trials will be required to establish the value of this approach to identify patients at risk for this type of proarrhythmia.

Does atrial fibrillation cause false-positive late potentials?

We hypothesized that atrial fibrillation may cause false-positive late potentials due to the recording of baseline atrial activity. We performed signal-averaged ECGs in 26 patients with atrial fibrillation before and after conversion to normal sinus rhythm. Signal-averaged ECGs were recorded for > 200 cycles with a noise level of < or = 0.5 microV. The signals were band-pass filtered at 40-250 Hz. We examined filtered QRS duration (fQRS), duration of low amplitude signal < 40 microV (LAS), and the root mean square (RMS) of the terminal 40 msec of the QRS complex. A late potential was considered present when two of the following three criteria were met: fQRS > or = 114 msec, LAS > or = 38 msec, and RMS < or = 20 microV. The mean +/- standard deviation of the fQRS in atrial fibrillation and sinus rhythm were 113 +/- 28 and 110 +/- 25 msec; of the LAS 38 +/- 17 and 37 +/- 15 msec; of the RMS 27 +/- 22 and 28 +/- 21 microV; of the noise 0.25 +/- 0.08 and 0.22 +/- 0.07 microV (P = NS). Ten signal-averaged ECGs in atrial fibrillation had late potentials. With reversion to sinus rhythm one of these 26 patients gained a late potential; two others lost a late potential (P = NS by McNemar's Chi-square). There was no significant difference in the signal-averaged ECG parameters or noise levels. In conclusion, signal-averaged ECG parameters are not significantly changed by cardioversion of atrial fibrillation to normal sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effects of dextro-amphetamine in the treatment of vasodepressor syncope.

Three patients with history of documented hypotension, near syncope, or syncope before or after the administration of isoproterenol during head-up tilt table are reported. Severe bradycardia was also noted in one patient. All three patients responded to the administration of 2.5 mg of oral dextroamphetamine 45 minutes prior to a repeat head-up tilt table study. The potent central and peripheral adrenergic agonist pharmacological properties of this drug permitted the prevention of severe vasodepressor syncope in these patients.

Inappropriate implantable cardioverter defibrillator shocks secondary to sensing lead failure: utility of stored electrograms.

The Ventritex Cadence is a fourth generation implantable cardioverter defibrillator that provides for retrieval of stored electrograms related to therapy. In two patients, this feature enabled us to troubleshoot sensing lead problems, in one instance before it became clinically apparent. This may be an important consideration in selecting an appropriate device.

Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block.

Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency-domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory (Holter) electrocardiography signal-averaging: a current perspective.

Signal-averaging is an emerging new application of the ambulatory ECG. Whereas real-time signal-averaging of the high-resolution ECG has led to the measurement of abnormal QRS complex parameters and to the detection of ventricular late potentials in patients with a history of ventricular tachycardia or fibrillation at increased risk of an arrhythmic event, similar measurements can also be derived from ambulatory ECG tape recordings. This review describes the technical differences between real-time and ambulatory high-resolution ECG signal-averaging, and the early clinical studies that correlated measured QRS complex parameters and defined the agreement of late potential detection with the two technologies. Although there appears to be a promising cost-effective benefit from ambulatory ECG signal-averaging, limitations imposed by the technical differences must be recognized, and additional investigation is needed to define the appropriate clinical use and criteria for best diagnostic and prognostic value.

In anterior myocardial infarction, frequency domain is better than time domain analysis of the signal-averaged ECG for identifying patients at risk for sustained ventricular tachycardia.

Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged ECG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40-250 Hz), the duration of the late QRS < 40 microV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location.