The history of the German Cardiac Society and the American College of Cardiology and their two founders.

The German Cardiac Society is the oldest national cardiac society in Europe, founded on June 3, 1927, in Bad Nauheim by Dr. Bruno Kisch and Professor Arthur Weber. They were actively supported by Dr. Franz Groedel, who together with Kisch became co-founders of the American College of Cardiology in 1949. Both Groedel and Kisch would be proud to see the fulfillment of their visions and dreams, which was commemorated at the joint session of the two societies held during the 78th annual meeting of the German Cardiac Society in Mannheim, Germany. "It is ironic that their dreadful years in Germany and their loss to German Cardiology helped to contribute to advances in American and international Cardiology," said Dr. Simon Dack, American College of Cardiology president in 1956 and 1957. The legacy of Groedel might be reflected by his own words: "We will meet the future not merely by dreams but by concerned action and inextinguishable enthusiasm".

Myocardial contrast echocardiography enhances long-term prognostic value of supine bicycle stress two-dimensional echocardiography.

BACKGROUND: The aim of this study was to determine the incremental prognostic value of myocardial contrast echocardiography (MCE) over two-dimensional echocardiography (2DE) in patients undergoing supine bicycle stress. METHODS: Eighty-four patients with known or suspected coronary artery disease who underwent supine bicycle stress with 2DE and MCE (mean age, 58.5 +/- 9.7 years; 68 men) were followed up for 48.3 +/- 8.9 months for cardiac death (n = 1), nonfatal myocardial infarction (n = 9), and revascularization (n = 20). RESULTS: In sequential Cox models, the predictive power of the clinical model was strengthened by 2DE (chi(2) = 7.73 vs 12.92, P = .02) and further improved by MCE (chi(2) = 19.04, P = .01). On multivariate analysis, the only independent follow-up event predictor was ischemia on MCE (hazard ratio, 6.79; 95% confidence interval, 2.02-22.82; P = .001). Among patients with normal results on 2DE, those with normal results on MCE had greater 4.5-year event-free survival than those with abnormal results on MCE (93% vs 69%, P = .01). CONCLUSIONS: MCE enhances the predictive power of supine bicycle stress 2DE and allows the risk stratification of patients with normal results on 2DE.

Historical perspectives of cardiac electrophysiology.

The diagnosis and treatment of clinical electrophysiology has a long and fascinating history. From earliest times, no clinical symptom impressed the patient (and the physician) more than an irregular heart beat. Although ancient Chinese pulse theory laid the foundation for the study of arrhythmias and clinical electrophysiology in the 5th century BC, the most significant breakthrough in the identification and treatment of cardiac arrhythmias first occurred in this century. In the last decades, our knowledge of electrophysiology and pharmacology has increased exponentially. The enormous clinical significance of cardiac rhythm disturbances has favored these advances. On the one hand, patients live longer and thus are more likely to experience arrhythmias. On the other hand, circulatory problems of the cardiac vessels have increased enormously, and this has been identified as the primary cause of cardiac rhythm disorders. Coronary heart disease has become not just the most significant disease of all, based on the statistics for cause of death. Arrhythmias are the main complication of ischemic heart disease, and they have been directly linked to the frequently arrhythmogenic sudden death syndrome, which is now presumed to be an avoidable "electrical accident" of the heart. A retrospective look--often charming in its own right--may not only make it easier to sort through the copious details of this field and so become oriented in this universe of important and less important facts: it may also provide the observer with a chronological vantage point from which to view the subject. The study of clinical electrophysiology is no dry compendium of facts and figures, but rather a dynamic field of study evolving out of the competition between various ideas, intentions and theories.

WPW syndrome: the 'Rosetta stone' of rhythmology. The history of the Rosetta stone.

Prior to the 'discovery' of the Wolff-Parkinson-White syndrome, interpreting the respective phenomena was akin to reading hieroglyphic characters; thus a clear pathophysiological understanding and practical clinical diagnosis were impossible. The epochal work by Wolff, Parkinson, and White, which resulted in the electrophysiologically correct interpretation of circus movements as the cause of tachycardic rhythm disorders, can therefore indeed be compared to the deciphering of hieroglyphic writing by Champollion in 1822 with the aid of the Rosetta stone. After intensive archaeological and graphological examinations by the Society of Antiquaries, the Rosetta stone finally made its way to the British Museum, where it can still be viewed and admired today.

Recovery from ultra-high dose organophosphate poisoning after "in-the-field" antidote treatment: potential lessons for civil defense.

Organophosphate poisoning is associated with a high mortality rate due to respiratory failure, dysrhythmias, and multi-organ failure. We report two cases of survival after "in-the field" antidote treatment of very severe organophosphate poisonings. Two patients orally ingested large amounts of the organophosphorous agent oxydemeton-methyl in suicide attempts, resulting in the hypercholinergic syndrome in both. Resuscitation included early administration of antidote by emergency medical personnel as well as high-dose atropine. Plasma levels of pseudo cholinesterase were initially very low in both patients. Long-term mechanical ventilation was necessary, and both patients developed aspiration pneumonia. At discharge, no major neurological deficits were present. Prompt antidote treatment and aggressive supportive emergency and intensive care unit therapy contribute to improved survival after acute organophosphate poisoning. We believe that in cases of mass poisonings--for example, terrorist activity--therapy must be available on the scene as soon as possible. This also may require decentralized antidote storage.

Impact of previous myocardial infarction on the incremental value of myocardial contrast to two-dimensional supine bicycle stress echocardiography in evaluation of coronary artery disease.

BACKGROUND: If compared to two-dimensional echocardiography (2DE), myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but data on MCE vs. 2DE during supine bicycle stress is limited. Although previous myocardial infarction (MI) influences sensitivity of 2DE, its effect on MCE has not been evaluated. OBJECTIVES: The study sought to determine the incremental benefit of MCE over 2DE for evaluation of CAD during supine bicycle stress and to assess the impact of previous MI on diagnostic values of both methods. METHODS: We studied 103 consecutive patients scheduled for coronary angiography. Prior to coronary angiography, all patients underwent supine bicycle stress. 2DE and MCE were performed during this stress test. The diagnosis of obstructive CAD (> or =50% stenosis) was based on the presence of inducible wall motion and perfusion abnormalities. RESULTS: Quantitative coronary angiography revealed > or =50% stenosis in 53 of 77 patients without previous MI and in 21 of 26 patients with previous MI. If compared to 2DE, MCE was more sensitive (68% vs. 86%; p<0.001) and more accurate (73% vs. 86%; p < 0.001) to detect > or =50% stenosis. In patients without previous MI, 2DE and MCE yielded sensitivity of 65% and 85% (p < 0.01) and accuracy of 71% and 85% (p < 0.01), whereas in patients with previous MI sensitivity was 79% and 90% (p=NS) and accuracy 79% and 88% (p = NS), respectively. CONCLUSIONS: MCE enhances sensitivity and accuracy of 2DE in detection of obstructive CAD during supine bicycle stress. The incremental benefit of MCE is especially present in patients without previous MI.

Past and future aspects of clinical electrophysiology.

The diagnosis and treatment of clinical electrophysiology has a long and fascinating history. From the earliest time, no clinical symptom impressed the patient (and the physician) more than an irregular heart beat. Although ancient Chinese pulse theory laid the foundation for the study of arrhythmias and clinical electrophysiology in the 5th century BC, the most significant breakthrough in the identification and treatment of cardiac arrhythmias first occurred in this century. In the last decades, our knowledge of electrophysiology and pharmacology has increased exponentially. The enormous clinical significance of cardiac rhythm disturbances has favoured these advances. On the one hand, patients live longer and thus are more likely to experience arrhythmias. On the other hand, circulatory problems of the cardiac vessels have increased enormously, and this has been identified as the primary cause of cardiac rhythm disorders. Coronary heart disease has become not just the most significant disease of all, based on the statistics for cause of death. Arrhythmias are the main complication of ischemic heart disease, and they have been directly linked to the frequent arrhythmogenic sudden death syndrome, which is now presumed to be an avoidable "electrical accident" of the heart. A retrospective look--often charming in its own right--may not only make it easier to sort through the copious details of this field and so become oriented in this universe of important and less important facts; it may also assist the observer in a chronological vantage point of the subject. The study of clinical electrophysiology is no dry compendium of facts and figures, but rather a dynamic field of study evolving out of the competition between various ideas, intentions and theories.

Automatic p wave analysis over 24 hours in patients with paroxysmal or persistent atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in the 24-hour-Holter-ECG of 60 patients with paroxysmal or persistent AF and 12 healthy subjects. METHODS: Recorded ECG signals were transferred to the analysis program where 5-10 P and R waves were manually marked. A wavelet transform performed a time-frequency decomposition to train neural networks. Afterwards, the detected P waves were described using a Gauss function optimized to fit the individual morphology and providing amplitude and duration at half P wave height. RESULTS: >96% of P waves were detected, 47.4 +/- 20.7% successfully analyzed afterwards. In the patient population, the mean amplitude was 0.073 +/- 0.028 mV (mean variance 0.020 +/- 0.008 mV(2)), the mean duration at half height 23.5 +/- 2.7 ms (mean variance 4.2 +/- 1.6 ms(2)). In the control group, the mean amplitude (0.105 +/- 0.020 ms) was significantly higher (P < 0.0005), the mean variance of duration at half height (2.9 +/- 0.6 ms(2)) significantly lower (P < 0.0085). CONCLUSIONS: This method shows promise for identification of triggering factors of AF.

Real time myocardial contrast echocardiography during supine bicycle stress and continuous infusion of contrast agent. Cutoff values for myocardial contrast replenishment discriminating abnormal myocardial perfusion.

BACKGROUND: Myocardial contrast echocardiography (MCE) is a new imaging modality for diagnosing coronary artery disease (CAD). OBJECTIVE: The aim of our study was to evaluate feasibility of qualitative myocardial contrast replenishment (RP) assessment during supine bicycle stress MCE and find out cutoff values for such analysis, which could allow accurate detection of CAD. METHODS: Forty-four consecutive patients, scheduled for coronary angiography (CA) underwent supine bicycle stress two-dimensional echocardiography (2DE). During the same session, MCE was performed at peak stress and post stress. Ultrasound contrast agent (SonoVue) was administered in continuous mode using an infusion pump (BR-INF 100, Bracco Research). Seventeen-segment model of left ventricle was used in analysis. MCE was assessed off-line in terms of myocardial contrast opacification and RP. RP was evaluated on the basis of the number of cardiac cycles required to refill the segment with contrast after its prior destruction with high-power frames. Determination of cutoff values for RP assessment was performed by means of reference intervals and receiver operating characteristic analysis. Quantitative CA was carried out using CAAS system. RESULTS: MCE could be assessed in 42 patients. CA revealed CAD in 25 patients. Calculated cutoff values for RP-analysis (peak-stress RP >3 cardiac cycles and difference between peak stress and post stress RP >0 cardiac cycles) provided sensitive (88%) and accurate (88%) detection of CAD. Sensitivity and accuracy of 2DE were 76% and 79%, respectively. CONCLUSIONS: Qualitative RP-analysis based on the number of cardiac cycles required to refill myocardium with contrast is feasible during supine bicycle stress MCE and enables accurate detection of CAD.

Role of high frequency atrial pacing for the termination of acute atrial fibrillation and atypical atrial flutter.

BACKGROUND: The aim of this study was to assess the efficacy of high-frequency (HF) pacing from the right atrial appendage (RAA) or coronary sinus ostium (CS-Os) for the termination of acute atrial fibrillation (AF) and atypical atrial flutter (AAFL) during an electrophysiological (EP) study. METHODS: 128 episodes of acute fast atrial arrhythmias (FAAs; 93 AF and 35 AAFL) were analyzed in 110 patients. Patients were initially observed for 60s leading to spontaneous termination of 28 FAAs. The remaining 100 FAAs (70 AF) episodes were randomized to the following strategies: (A) pacing at RAA using up to 10 consecutive 20-Hz trains followed by the same stimulation protocol at CS-Os if RAA pacing failed, (B) pacing at CS-Os using the same stimulation protocol followed by HF pacing at RAA, or (C) observation up to 6 minutes ("no pacing"). RESULTS: The 20-Hz pacing at both RAA and CS-Os was associated with higher conversion of AAFL, as compared to strategy C (60% and 77% vs 11%; P < 0.05). Only HF pacing at CS-Os was superior to observation strategy for the conversion of AF (21% vs 4%; P < 0.05). CONCLUSIONS: The 20-Hz pacing protocol is superior to observation strategy for interruption of either acute AF or acute AAFL episodes; however, its efficacy is higher in AAFLs. These results can be helpful for the termination of acute atrial tachyarrhythmias during EPstudy and should be further evaluated in patients with implantable devices capable of antitachycardia pacing.

Echocardiographic assessment of left ventricular mass in neonatal and adult mice: accuracy of different echocardiographic methods.

Echocardiography is an established method to estimate left-ventricular mass (LVM) in mice. Accuracy is determined by cardiac size and morphology and influenced by mathematical models. We investigated accuracy of three common algorithms in three early developmental stages. High-resolution echocardiography was performed in 35 C57/BL6-mice. Therefore, two-dimensional-guided M-mode echocardiography and parasternal short- and long-axis views in B-mode were obtained. LVM was assessed in vivo applying Penn (P), Area Length (AL), and Truncated Ellipsoid (TE) algorithms and validated with histomorphometry. Regression analysis of all mice showed fair estimation of LVM assessed with M-mode-based Penn algorithm (y = 0.6*x - 0.12, r: 0.71). In contrast two-dimensional assessment of LVM revealed close linear relationship with histomorphometry (y(AL)= 1.21*x - 12.1, r: 0.88, y(TE)= 1.38*x - 2.88, r: 0.86). Bias was lowest for LVM-AL at diastole underestimating 3.2%. In concordance with the summarized data, LVM-P revealed lower regression coefficients and significant underestimation in all three subgroups. Small hearts (<50 mg, n = 12) correlated best with LVM-AL at systole. Hearts of adolescent (50-75 mg, n = 13) and adult (75-100 mg, n = 10) mice revealed close linear relationship with LVM-AL and LVM-TE at diastole. Echocardiographic assessment of LVM is feasible in hearts weighting less than 50 mg and can be estimated best in systole. Hearts weighting more than 50 mg are estimated most accurately by means of LVM-AL at diastole.

Persistence of iatrogenic atrial septal defect after pulmonary vein isolation--an underestimated risk?

BACKGROUND: According to present knowledge, pulmonary vein isolation (PVI) bears a low interventional risk and has a high feasibility. For completion of PVI, left atrial access is achieved via single or double transseptal puncture. We sought to determine the incidence and echocardiographic characteristics of persistent iatrogenic atrial septal defect (iASD) after PVI. Further objectives were to define clinical and periprocedural risk factors for the development of iASD. METHODS: Every patient admitted for PVI at our hospital was screened for eligibility for study participation. Exclusion criteria were inability for undergoing transesophageal echocardiography, preexisting atrial septal defect, open-heart surgery or another transseptal procedure during the follow-up period. Transesophageal echocardiography was performed before PVI and after 9 months. Interatrial shunt was characterized by echocardiographic parameters; right-to-left-shunting (RLS) was quantified by contrast echocardiography. RESULTS: Forty-two patients were included, 27 patients underwent PVI with single transseptal puncture and additional advancement of a second electrophysiologic catheter (group A) 15 patients underwent PVI with double transseptal puncture (group B). In 8 patients of group A, iASD persisted after the follow-up period, including 6 patients with distinct RLS. We saw no iASD in group B (P = .011, CI -0.79 to -0.11). Preprocedural pulmonary artery pressure was significantly higher in patients with iASD and accompanying RLS, compared with patients with iASD and no evidence of RLS (23.75 +/- 0.50 vs 17.59 +/- 5.82, P = .048, CI 0.048-12.27). CONCLUSION: This is the first study that demonstrates a high incidence of long-term persistent iatrogenic atrial septal defect with RLS after PVI. All interatrial shunts occurred after single transseptal puncture with passage of 2 electrophysiologic catheters into the left atrium. Increased preprocedural pulmonary artery pressure seems to promote the occurrence of RLS across iASD.

Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial.

AIMS: Treatment of atrial fibrillation remains a major clinical challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease. METHODS AND RESULTS: To evaluate the efficacy of azimilide, a new class III anti-arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned electrical cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy analysis was based on event recurrence, which was defined as atrial fibrillation lasting>24 h, or requiring DC cardioversion. Median time to recurrence was 14 days for azimilide, 12 days for placebo, and 28 days for sotalol (P=0.0320 when comparing azimilide with placebo; P=0.0002 when comparing azimilide with sotalol). The placebo-to-azimilide hazard ratio was 1.291 (95% CI: 1.022-1.629) and the sotalol-to-azimilide hazard ratio was 0.652 (95% CI: 0.523-0.814). Adverse events causing patient withdrawal were more frequent (P<0.01) in patients on azimilide (12.3%) and on sotalol (13.9%) than on placebo (5.4%). Eight patients in the sotalol (3.5%) and 16 in the azimilide (7.6%) group interrupted the study because of QTc prolongation. Torsade de pointes was reported in five patients of the azimilide group. The percentage of patients who completed the 26 week study period without events were 19% for azimilide, 15% for placebo, and 33% for sotalol (P<0.01). Unsuccessful day 4 cardioversion, arrhythmia recurrence, and adverse events were the main causes of withdrawal from the study. CONCLUSION: This study demonstrates that the anti-arrhythmic efficacy of azimilide is slightly superior to placebo but significantly inferior to sotalol in patients with persistent AF. The modest anti-arrhythmic efficacy and high rate of torsade de pointes and marked QTc prolongation limit azimilide utilization for the treatment of AF.

[Atrial fibrillation: current therapeutic options]. / Vorhofflimmern: therapeutische Möglichkeiten.

The treatment of atrial fibrillation still remains challenging in everyday practice. Even after the introduction of catheter ablation, the decision making about the type of therapy became more complex. The recently published guidelines of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology clearly show therapeutic approaches for different types of atrial fibrillation. The fear of thromboembolism still forces the physician to restore sinus rhythms and perform a perfect anticoagulation. Based on large studies, we are able to decide for each patient individually whether oral anticoagulation or acetylsalicylic acid/clopidogrel are required. Future studies in a large cohort of patients are still necessary to clarify the value of interventional therapy in conjunction with antiarrhythmic drug therapy. These will provide patients with a safe therapy and high quality of life despite presenting paroxysmal or persistent atrial fibrillation.

Identification of "substrate fibrillators" and "trigger fibrillators" by pacemaker diagnostics.

BACKGROUND: The population of patients likely to respond to selected pacing algorithms for maintenance of sinus rhythm is unknown. OBJECTIVES: The purpose of this study was to identify patients with specific onset patterns of paroxysmal atrial fibrillation (AF). METHODS: Dual-chamber pacemakers with advanced diagnostic functions were implanted in 112 patients with conventional indications for antibradycardia pacing and a history of paroxysmal AF. Pacemaker diagnostic data were analyzed after 97.5 +/- 40.9 days. According to the frequency of premature atrial contractions (PACs) during the 5 minutes before AF onset, patients were assigned to one of three groups: group A (high PAC activity), group B (moderate PAC activity), or group C (low PAC activity). RESULTS: AF burden was lower in group A (4.6% +/- 2.4%) than group B (15.8% +/- 3.0%, P = .003) and group C (15.5% +/- 3.1%, P = .003). Fewer AF episodes occurred in group A (2.1 +/- 1.3 per day) than group B (3.8 +/- 1.2 per day, P = .006). Mean AF episode duration was shorter in group A (11.4 +/- 10.2 hours) than group C (41.4 +/- 27.5 hours, P = .03). CONCLUSION: The coincidence of low PAC activity before AF onset, high AF burden, and extended arrhythmia episode duration appears to be the consequence of a high atrial substrate factor. In these "substrate fibrillators," the efficacy of pacing algorithms for maintenance of sinus rhythm may be limited. In contrast, "trigger fibrillators" exhibiting low AF burden despite high PAC incidence may represent the target population for specific PAC-suppressing pacing algorithms.

Pro-arrhythmic effects of amiodarone and concomitant rate-control medication.

AIMS: Amiodarone is one of the most efficient and safe antiarrhythmic drugs in the treatment of atrial fibrillation (AF). Although pro-arrhythmic effects of amiodarone therapy are rare, the aim of the present study was to identify clinical constellations which may lead to amiodarone-associated pro-arrhythmia. METHODS AND RESULTS: Sixty-three consecutive patients (pts) (49 males; 64+/-10.3 years; 35 with coronary heart disease, 17 with lone AF) were retrospectively included in this study. All received an oral (92.1%) or i.v. (7.9%) loading dose of amiodarone for the treatment of AF. Cardiac diseases, concomitant medical treatment, and incidence of pro-arrhythmic effects were analysed. Three pts (4.8% of the total population) developed a clinical relevant, polymorphic ventricular tachyarrhythmia, 3-48 h after initiation of amiodarone loading. Coronary heart disease was present in all of these pts, and in two of them left ventricular ejection fraction was severely reduced. The mean QTc in these pts was only slightly prolonged; mean heart rate was significantly decreased compared with the total study population (61.0+/-7.5 vs. 74.5+/-24.1 bpm; P < or = 0.05). In all pts with pro-arrhythmia, amiodarone (two pts i.v., one patient oral) was initiated during concomitant beta-blocker/digitalis therapy. Twenty-five per cent of the patients receiving this 'triple' therapy developed ventricular arrhythmia. CONCLUSION: The present study implies that initiation of amiodarone therapy in pts with structural heart disease and AF that are concomitantly treated with beta-blockers and digitalis may have an increased risk of amiodarone-associated pro-arrhythmia.

Atrial thrombi-a prospective follow-up study over 3 years with transesophageal echocardiography and cranial magnetic resonance imaging.

BACKGROUND: Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients under oral anticoagulation. METHODS: Consecutive patients with persistent or permanent AF and left atrial (LA) thrombi were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 3 years. Oral anticoagulation was continued or initiated in all patients. A target INR of 2.5 was intended in all patients. RESULTS: Forty-three patients with LA thrombi and persistent or permanent AF were included. During the follow-up period 31(72%) of the thrombi disappeared. Patients with disappearance of thrombi had significantly smaller thrombi (P < 0.01), a lower echogenicity of thrombi (P < 0.01), and a lower LA volume (P = 0.02). Twenty-two (51%) patients suffered from cerebral embolism and/or death during the observation period. Five patients died due to embolic events. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (P < 0.001) and a history of previous thromboembolism (P < 0.01). CONCLUSIONS: Patients with persistent or permanent AF and atrial thrombi have a high long-term risk of cerebral embolism and/or death (51%) even despite the oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.