Cardiac catheterization is among the most performed medical procedures in the modern era. There were sporadic reports indicating that cardiac arrhythmias are common during cardiac catheterization, and there are risks of developing serious and potentially life-threatening arrhythmias, such as sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and high-grade conduction disturbances such as complete heart block (CHB), requiring immediate interventions. However, there is lack of systematic overview of these conditions.

To systematically review existing literature and gain better understanding of the incidence of cardiac arrhythmias during cardiac catheterization, and their impact on outcomes, as well as potential approaches to minimize this risk.

We applied a combination of terms potentially used in reports describing various cardiac arrhythmias during common cardiac catheterization procedures to systematically search PubMed, EMBASE and Cochrane databases, as well as references of full-length articles.

During right heart catheterization (RHC), the incidence of atrial arrhythmias (premature atrial complexes, atrial fibrillation and flutter) was low (< 1%); these arrhythmias were usually transient and self-limited. RHC associated with the development of a new RBBB at a rate of 0.1%-0.3% in individuals with normal conduction system but up to 6.3% in individuals with pre-existing left bundle branch block. These patients may require temporary pacing due to transient CHB. Isolated premature ventricular complexes or non-sustained VT are common during RHC (up to 20% of cases). Sustained ventricular arrhythmias (VT and/or VF) requiring either withdrawal of catheter or cardioversion occurred infrequently (1%-1.3%). During left heart catheterizations (LHC), the incidence of ventricular arrhythmias has declined significantly over the last few decades, from 1.1% historically to 0.1% currently. The overall reported rate of VT/VF in diagnostic LHC and coronary angiography is 0.8%. The risk of VT/VF was higher during percutaneous coronary interventions for stable coronary artery disease (1.1%) and even higher for patients with acute myocardial infarctions (4.1%-4.3%). Intravenous adenosine and papaverine bolus for fractional flow reserve measurement, as well as intracoronary imaging using optical coherence tomography have been reported to induce VF. Although uncommon, LHC and coronary angiography were also reported to induce conduction disturbances including CHB.

Cardiac arrhythmias are common and potentially serious complications of cardiac catheterization procedures, and it demands constant vigilance and readiness to intervene during procedures.

Hypotension, bradycardia, and contrast induced chest pain are potential complications of cardiac catheterization and coronary angiography. Catheter-induced coronary spasm has been occasionally demonstrated, but its relationship to spontaneous coronary spasm is unclear. We describe a 64-year-old female who underwent coronary artery bypass surgery in 1998 on the basis of an angiographic diagnosis of severe left main disease, who recently presented with increasingly frequent typical angina. Repeat coronary angiography was immediately complicated by severe chest pain, hypotension, and bradycardia but demonstrated only mild disease of the left main artery and entire coronary tree with complete occlusion of her prior grafts. This reaction was almost identical to that observed during her original coronary angiogram. We now believe her original angiogram was complicated by severe catheter-induced left main spasm, with the accompanying contrast reaction attributed to left main disease, and the occlusion of coronary grafts explained by the absence of significant left main disease. The combination of these symptoms has not been documented in the literature. In this instance, these manifestations erroneously led to coronary bypass surgery. It is unknown whether routine, systematic injection of intracoronary nitroglycerin prior to angiography might blunt the severity of such reactions.

To compare the frequency of adverse events after cardioangiography with iohexol and iodixanol in an unselected patient population with special regard to previously defined "risk patients": age> or =65 years, severe coronary artery disease, unstable angina pectoris and left ventricular dysfunction.

A total of 1020 patients referred to cardioangiography were included in this open, prospective cross-sectional study, comparing iodixanol (320 mgI/ml) and iohexol (350 mgI/ml). Adverse events were recorded and the patients answered a questionnaire.

Cardiac adverse events (CAE) i.e., angina pectoris, arrhythmia and dyspnea within 24 h of examination were reported by 9% of patients receiving iohexol and by 7% receiving iodixanol. Two cases of ventricular fibrillation occurred, both after iohexol. The proportion of CAE was 11% for patients> or =65 years receiving iohexol and 7% in younger patients. For patients receiving iodixanol the proportion was 7%, in both age groups. Patients with severe coronary disease had more CAE than less ill patients in both CM groups. The proportion of unstable patients with CAE was 18% in the iohexol group and 12% in the iodixanol group. Left ventricular dysfunction was not related to CAE.

Iodixanol could be advantageous in patients with unstable angina.

Cerebral embolization has been documented as one of the complications of diagnostic heart catheterization by transcranial Doppler (TCD). This study aimed to evaluate our hypothesis that the nature of embolic signals involved in different stages of catheter manipulation may be distinct. TCD-detected cerebral emboli occurring at different phases of cardiac catheterization were registered and differentiated by comparing their acoustic signatures with the Doppler signals generated from clinically frequently encountered embolic materials in an in vitro middle cerebral artery model. We found that there was a significant difference in embolic signal intensity and duration between different phases of cardiac catheterization. Our data suggest that different types of emboli may be involved in different phases of the catheterization. Cathet Cardiovasc Intervent 2001;53:323-330.

To compare the electrophysiological effects of two contrast media (CM), the non-ionic dimer iodixanol and the ionic dimer ioxaglate using computerised dynamic vectorcardiography (VCG) during coronary angiography.

The study was designed as a double-blind, three-period crossover, randomised comparison between iodixanol (320 mg I/ml) and ioxaglate (320 mg I/ml). Group 1 (HVV) received ioxaglate (H) in the first injection in the left coronary artery (LCA) and iodixanol (V) in the following injections. Group 2 (VHH) received iodixanol in the first injection in LCA and ioxaglate in the following injections. The first three injections in the LCA were subjected to electrocardiographic analysis.

For five out of six VCG variables, there was a significant difference in response between iodixanol and ioxaglate. For these five variables, the deviations from baseline were greater in the ioxaglate than in the iodixanol group (P<0.05). The most pronounced effects from ioxaglate were seen on the ST-segment and T-wave.

Iodixanol caused less pronounced electrophysiological changes than ioxaglate, especially during the repolarisation phase. Vectorcardiography is a sensitive and reproducible technique for detecting electrophysiological effects induced by CM.

Previous studies have proposed that sodium supplement to nonionic contrast media (CM) can decrease the risk of ventricular fibrillation (VF). This study was designed to compare the occurence of VF induced by ioxilan (containing 9 mmol/LNa+) with other nonionic CMs. After wedging a catheter in the right coronary artery, test solutions including ioxilan, ioversol, iomeprol, and iopromide were infused for 30 sec at the rate of 0.4 ml/sec or until VF occurred. Then, incidence of VF, contact time (i.e. the time required to produce VF), and QTc were measured. Also, the CMs other than ioxilan were investigated at sodium levels adjusted to 9 and 20 mmol/L Na+. The incidence of VF with ioxilan (0%) was the lowest of all. In the other CMs, the incidence decreased in accordance with increase of sodium. Iomeprol and iopromide showed significant reduction of VF incidence at the sodium level of 20 mmol/L. The higher sodium supplements also prolonged the contact times. The increase of QTc was the greatest in ioxilan. Ioxilan has the least arrythmogenic property among the current low-osmolality nonionic CMs. This property might be attributable to an optimal sodium concentration of 9 mmol/L in the CM.

We investigated the possible cardiac effects of oxygen addition to contrast media (CM) during coronary arteriography in dogs that did and did not have ischemic heart failure.

Acute ischemic heart failure was induced by injecting small plastic microspheres into the left coronary artery of 18 dogs. Hemodynamic and electrophysiologic measurements were performed during a single injection before and during heart failure and during a single injection and five rapidly repeated CM injections during heart failure. Iohexol supplemented with electrolytes (iohexol + electrolytes = IPE), oxygenated IPE (IPE+O), Ringer acetate, and oxygenated Ringer acetate were injected into the left coronary artery.

Single injections of IPE and IPE+O induced small hemodynamic and electrophysiologic effects. However, repeated injections of IPE and IPE+O increased left ventricular inotropy (maximum value of the first derivative of the left ventricular pressure) by 36% and 39%, reduced heart rate by 7% (for both), and lengthened QTc time (corrected QT interval) by 39 and 38 msec, respectively. A comparison of IPE and IPE+O revealed no statistically significant differences.

Although electrolyte addition to nonionic CM may reduce the risk of cardiac complications during coronary arteriography, oxygenation does not seem to significantly further reduce this risk.

Small electrolyte additions to a nonionic contrast medium reduce the risk of ventricular fibrillation (VF) during wedged catheter injection of a contrast medium. The current study was designed to further investigate contrast-medium-induced VF by studying the effect of pretreatment with different antiarrhythmic drugs.

During a simulated wedged catheter situation, iohexol was injected into the anterior descending branch of the left coronary artery in five open-chest, anesthetized dogs pretreated with lidocaine, propranolol, amiodarone, almokalant, or verapamil.

Wedging the catheter for 60 sec did not induce VF. However, all 15 wedged catheter injections with iohexol induced VF within 28 sec (19 +/- 1 [mean +/- standard error of the mean]) despite pretreatment with antiarrhythmic drugs. Prior to VF, conduction was slowed and monophasic action potential duration lengthened in the contrast-medium-perfused myocardium, although no significant changes occurred in the control area.

The combination of catheter wedging and long-lasting contrast medium injection has a high risk of causing VF. Although adding a small amount of electrolytes to nonionic contrast media can reduce the risk of VF, antiarrhythmic drug therapy may not have a protective effect.

We investigated the cardiac effects of single and repeated contrast media injections in dogs with heart failure and compared the effects of iohexol with iohexol supplemented with electrolytes (30 mmol/l NaCl, 0.15 mmol/l CaCl2, 0.9 mmol/l KCl, and 0.1 mmol/l MgCl2; iohexol + electrolytes [IPE]). Although it has a higher osmolality than iohexol, IPE appears to be safer when injected through a wedged catheter.

Acute ischemic heart failure was induced by injections of small plastic microspheres into the left coronary artery of 16 anesthetized dogs. Iohexol, IPE, and Ringer acetate were injected into the left coronary artery either as a 5-ml single injection or repeatedly five times, once every 10th second.

Single injections of iohexol and IPE induced small hemodynamic and electrophysiologic effects. However, repeated injections of iohexol and IPE increased the maximum rate of isovolumetric contraction by 46% and 36%, reduced heart rate by 8% and 7%, and lengthened QTc (the Q-T interval corrected for heart rate) time by 44 and 39 msec, respectively. No statistically significant differences were found in a comparison of IPE and iohexol.

During heart failure, repeated injections of iohexol and IPE induced similar additive hemodynamic and electrophysiologic effects without inducing arrhythmias or serious hemodynamic changes.

The purpose of this study was to determine whether an adverse interaction exists between radiographic contrast agents and thrombolytic drugs.

Coronary thrombosis may occur in the setting of unstable angina and after coronary angioplasty. However, the use of thrombolytic drugs in the setting of unstable angina has not been beneficial and, in one large trial of angioplasty in patients with unstable angina, was associated with an increased incidence of ischemic complications and abrupt closure. The reasons for these results are not clear. Coronary arteriography was performed in many of these trials, and it is known that fibrin structure and assembly are altered by radiographic contrast agents.

Blood samples were obtained from patients before (n = 25) and after (n = 20) angiography using iohexol. Blood samples obtained before angiography were tested for response to streptokinase (10 and 100 IU/ml), urokinase (100, 200 and 500 IU/ml) and recombinant tissue-type plasminogen activator (rt-PA) (100 and 1,000 IU/ml) and the results measured. Iohexol, diatrizoate or ioxaglate (4% by volume) was added to separate aliquots of the baseline sample, and the test was repeated. Blood samples obtained after angiography were tested in a similar manner.

The onset of lysis at baseline by rt-PA at 1,000 IU/ml occurred at 72 +/- 8.2 s (mean +/- SD) and was markedly delayed in the presence of diatrizoate (527 +/- 181.7 s, p < 0.001) or iohexol (460 +/- 197.0 s, p < 0.001) but not ioxaglate. At 100 IU/ml, there was no lysis detected with rt-PA after the addition of any contrast agent. The addition of a contrast agent caused similar delays in the onset of lysis by urokinase and streptokinase; similar to rt-PA, the effect was smaller at higher concentrations of drug. In vivo blood samples obtained from the patient after angiography showed delays in the onset of lysis by rt-PA and urokinase but not streptokinase.

These data demonstrate that radiographic contrast agents impede fibrinolysis. This previously undescribed interaction was demonstrated using an in vitro test system, but these findings may have clinical relevance when thrombolytic drugs are used at the time of angiography.

Contrast media are used as substances for visualization of vascular system. But, their administration is often associated with thromboembolic complications. The purpose of this study is to evaluate the thrombogenic action of ionic and non-ionic contrast media on thrombus formation. The experimental destruction of endothelial cells by Laser injury leads to thrombus and emboli formation. Two ionic and two non-ionic contrast media were injected intravenously via penis vein and tested at various dosages (1.0 and 2.5 ml/kg) 5, 30, 45 and 65 minutes after injection. The administration of these contrast media decreases the number of Laser injuries required to induce thrombus formation, increases the number of emboli which detached from thrombus and prolongs duration of embolization (p < or = 0.05). These experimental results suggest that ionic and non-ionic contrast media induce thrombogenic effects. This thrombogenicity was the greatest for non-ionic contrast media. It was observed the decrease of the white cells, red cells and platelets.

Patient safety should be in focus when using contrast media (CM) in diagnostic and interventional cardiac procedures. Side-effects that occur during cardioangiography due to hemodynamic effects of CM include direct effects on the heart, effects on the systemic and pulmonary circulation, and effects on the blood volume. Although not a totally inert solution, iodixanol (Visipaque) has less pronounced direct inotropic effects on the heart than have other CM; its vasodilatory effects on peripheral arteries are smaller, and the increase in blood volume is smaller after administering iodixanol than after other CM. Thus, iodixanol represents a further step forward in terms of reducing side-effects during contrast-enhanced diagnostic and interventional cardiac procedures.

Contrast media (CM) affect normal cardiac electrophysiology when injected into the coronary arteries. High-osmolality CM cause more pronounced electrophysiological effects than do low-osmolality CM. Further, both high- and low-osmolality ionic CM have more pronounced effects than the nonionic CM. The CM-induced electrophysiological effects involve regional disturbances of depolarization and repolarization, thereby causing disturbances of impulse conduction as well as dispersion of refractoriness. Recent experimental studies have demonstrated that the addition of sodium or a balanced electrolyte supplement to nonionic CM reduces the risk of ventricular fibrillation (VF), particularly when the CM is injected in a wedged catheter situation. The reduced risk of VF may be due to the small and transient lengthening of repolarization seen in the CM-perfused area of the myocardium. Iodixanol, which is an isotonic nonionic dimer supplemented with NaCl and CaCl(2), is as well tolerated as iohexol during free coronary flow. However, when flow is restricted, such as when CM is injected through a wedged catheter, the risk of VF is less with iodixanol than with iopamidol, iohexol and ioxaglate.

This study was designed to compare the cardiac electrophysiology and mechanical effects of iodixanol to those of iotrolan, iopromide, ioxaglate and diatrizoate. Two consecutive injections of contrast media (CM) (0.3 g I/kg and 0.9 g I/kg b.w.) were given to spontaneously beating, Langendorff-perfused rat hearts. CM were given as a single, short-lasting bolus injection (i.e. over 2 and 5 s). Changes in aortic pressure, left ventricular pressures and ECG were continuously recorded during constant volume perfusion. The nonionic CM had less pronounced effects on aortic pressure than had the ionic media. The peak rate of isovolumetric contraction (LV dP/dt(max)) was slightly decreased by iodixanol and iotrolan, slightly more decreased by iopromide and markedly decreased by ioxaglate and diatrizoate. Similarly, the peak rate of pressure decline (LV dP/dt (min)) was only slightly decreased by iodixanol and iotrolan. Also, the 2 nonionic dimers had the smallest effects on the left ventricular end diastolic pressure (LVEDP) and heart rate. Ioxaglate lengthened the PQ-interval, but less so than diatrizoate. THe QT-interval was only slightly lengthened by iodixanol and iotrolan, as compared to the lenghthening caused by iopromide, ioxaglate and diatrizoate. Single ventricular extrasystoles were seen in all groups. Extrasystoles up to 3 coupled beats were registered after ioxaglate and diatrizoate. No episodes of ventricular fibrillation occurred with any CM. In conclusion, the nonionic dimers, and in particular iodixanol, induce only minor changes in cardiac function, whereas the ionic dimer ioxaglate and the ionic monomer diatrizoate induce pronounced effects.

We studied the effect of the addition of sodium to nonionic contrast medium (CM) on the incidence of ventricular fibrillation (VF) during coronary arteriography in dogs.

We infused 20 ml (0.5 ml/sec) of iohexol, iohexol plus 30 mmol of Na+ per liter, and NaCl-Ringer's acetate in randomized order through a wedged catheter placed in the right coronary artery (RCA) or in the left anterior descending coronary artery (LAD) in 12 anesthetized dogs. In addition to electrocardiographic and hemodynamic measurements, epicardial monophasic action potential durations and ventricular activation times were recorded during infusions into the LAD.

All infusions with iohexol into the RCA and the LAD (n = 16) caused VF. Seven of 19 infusions with iohexol plus 30 mmol of Na+ per liter caused VF. Infusions with iohexol plus 30 mmol of Na+ per liter that did not cause VF lengthened monophasic action potential durations and increased ventricular activation times more in the CM-perfused area than in the control area.

The addition of sodium to iohexol reduces the incidence of VF when infused through a wedged catheter. The protective mechanisms may be attributable to a lengthened repolarization phase and an increased activation time in the CM-perfused area.

We investigated the cardiac effects of an ionic dimer, ioxaglate and two nonionic dimers, iotrolan, and iodixanol.

During a simulated wedged catheter situation, 22 ml of each contrast medium was injected into the left anterior descending branch of the left coronary artery in seven open-chested, anesthetized dogs.

Of 13 injections with each contrast medium, ioxaglate induced ventricular fibrillation in 11 after 34 +/- 5 sec, iotrolan in 6 after 42 +/- 4 sec, and iodixanol in 3 after 61 +/- 1 sec. Ioxaglate markedly lengthened monophasic action potential duration in contrast medium-perfused myocardium. Iotrolan, and iodixanol induced biphasic changes, first lengthening and then shortening action potential duration. The electrophysiological changes occurred later when using iodixanol.

The risk of ventricular fibrillation during long-lasting contrast media exposure to the myocardium, as in a wedged catheter situation, appears to be much lower with iodixanol compared with ioxaglate and also lower than when using iotrolan.

Cardiac tamponade secondary to ventricular wall perforation is one of the possible complications of right-sided as well as left-sided cardiac catheterization. Ventriculography was performed on a patient with obstructive cardiomyopathy using a nonionic contrast medium. During the procedure, the right ventricle was accidentally perforated and the patient developed cardiac tamponade. Pericardiocentesis was unsuccessful and surgical drainage was needed after the patient developed progressive hemodynamic deterioration. At surgery, pericardial thrombus was found. We consider the reason for failure of pericardiocentesis was rapid coagulation of the extravasated blood in connection with nonionic contrast material.

Radiographic contrast agents are essential for the performance of coronary angiography and angioplasty. Historical data show that thrombosis-related events have occurred since coronary angiography has been performed. Newer non-ionic agents have been shown to be safer than conventional high osmolar ionic agents especially in high risk patients, but concern has been raised about a potentially increased risk of thrombosis with the use of these agents. A review of basic and clinical evidence for this perception does not support the view that an increase in thrombosis-related events has occurred as a results of non-ionic contrast media use in coronary angiographic procedures.

To evaluate the occurrence of complications during diagnostic or interventional catheterization a retrospective analysis of catheterization procedures in 12 Italian laboratories using the nonionic contrast medium (CM) iopamidol (370 mgI/ml) was performed. Data obtained on 26,219 patients greater than or equal to 14 years are presented. The overall complication rate was 1.89% (485/26,219). The overall mortality rate was 0.1% (27/26,219). Procedure related complications were 389 (1.48%) and CM related complications were 106 (0.4%). No death was attributed to CM. Ventricular fibrillation (VF) rate was 0.11% comparable to the low rate observed with nonionic CM in other studies and less than the rate observed in surveys concerning the use of ionic CM. Fifty-seven thrombotic events were recorded (0.22%), a rate comparable with other surveys with ionic and nonionic CM. The total complication rate (6.1%), the rates of coronary occlusion (1.34%), myocardial infarction (0.37%) and urgent coronary artery by-pass grafting (0.5%) in 1,348 coronary angioplasties were lower than those recorded in previous surveys. These data confirm a good tolerability and no increased risk of VF and thrombotic events with iopamidol in cardiac catheterization.

To review the incidence, definition, clinical course, risk factors, pathogenesis and prevention of contrast-associated nephropathy (CAN) following cardiac angiography with emphasis on differences between high-osmolality contrast media (HOCM) and low-osmolality contrast media (LOCM).

Investigations in animal models and in patients following cardiac angiography.

Animal models of the pathogenesis of CAN are presented. Human studies describing the incidence, clinical course, risk factors, and prevention of CAN are reviewed. Comparative clinical trials of HOCM (diatrizoate, metrizoate) and LOCM (iohexol, iopamidol, ioxaglate) nephrotoxicity following cardiac angiography are critically evaluated.

All clinical studies comparing CAN of HOCM versus LOCM following cardiac angiography have some methodologic limitations (e.g., small sample size, lack of control for other factors) that may affect renal function, lack of stratification for other reported risk factors, and variable or short follow-up periods.

Whether the incidence of CAN following cardiac angiography is reduced with LOCM remains controversial. The incidence of CAN in patients with normal renal function does not appear to differ in patients treated with LOCM versus HOCM because few patients in each group develop renal failure. Additional controlled clinical trials comparing CAN of LOCM and HOCM in patients with renal dysfunction are needed. Because of greater product cost and scarcity of documented benefit compared with HOCM, selection of LOCM based on the presence of renal dysfunction cannot be recommended at this time.

Ionic and nonionic contrast materials are similarly efficacious in providing excellent images with minimal risk to the patient. In comparison with ionic media, the nonionic agents produce minor alterations in intracardiac and peripheral pressures as well as in electrocardiographic intervals and morphology. In addition, nonionic media are less often associated with undesirable symptoms, such as flushing and vomiting. At the same time, ionic and nonionic media are accompanied by a similar incidence of nephrotoxicity, serious arrhythmias, and death. Finally, nonionic contrast material is substantially more expensive than ionic media. In light of this marked difference in cost, one could argue that nonionic media should be reserved for "high-risk" patients, that is, those with a history of a serious adverse reaction to ionic contrast media and those in whom contrast-induced hypotension would be particularly deleterious.

Contrast agents are used as diagnostic molecules for the visualization of the vascular system. Despite their rapid pharmacokinetic distribution, and their excretion within a few minutes, their injection is associated with clinical symptoms of relative bioincompatibility. Allergoid reactions and disturbances of the hemostatic system represent the main fields of biological investigations. Due to the extent of clinical and experimental works the ubiquitous interactions between these molecules and cellular and/or protein systems have emerged. The development of a new family of low osmolality ionic or non-ionic contrast molecules had decreased the incidence of minor reactions, but did not modify the frequency of severe accidents and even led to the emergence of new iatrogenic syndromes. Despite extensive laboratory investigations there are still no predictive criteria nor any specific therapeutic prevention of these allergoid reactions. The suggested future line of investigation concerns the physicochemical interaction of CM and targeted biological systems which may allow the analysis and predictivity of these interactions at the molecular level.

The evolution of contrast material for intravascular use has been directed toward the development of better-tolerated agents. Currently, a variety of such "dyes" are available for coronary angiography and left ventriculography. Considerable animal and human investigation suggests that significant differences exist between the families of contrast agents that relate to patient tolerance. The newer low osmolality agents (especially the nonionic agents) produce less perturbation of the homeostatic state, which is clinically manifested by a lessened incidence of side effects, including those of a hemodynamic and electrophysiologic nature. While controversy continues over the cost/benefit ratio of the low osmolality contrast agents compared to traditional high osmolality agents, the former are rapidly becoming the community standard for diagnostic and especially therapeutic cardiologic procedures. Accepting the advantages of the low osmolality contrast agents, differences between the ionic dimers and the nonionic agents have been examined. Both experimental and clinical data suggest superiority of the nonionic agents. Although controversy still surrounds the issue of thromboembolism with the nonionic agents, accumulating evidence fails to support a clinically significant relation. The choice of contrast material is the responsibility of the invasive cardiologist. While the benefits of low osmolality agents are most obvious in high-risk patients, experience with large-scale intravenous studies suggests that the choice of contrast agent is a better discriminator of adverse reaction than is preprocedural risk stratification.