Lukas Kappenberger

Angiographic follow-up after placement of a self-expanding coronary artery stent

BACKGROUND The placement of stents in coronary arteries after coronary angioplasty has been investigated as a way of treating abrupt coronary-artery occlusion related to the angioplasty and of reducing the late intimal hyperplasia responsible for gradual restenosis of the dilated lesion. METHODS From March 1986 to January 1988, we implanted 117 self-expanding, stainless-steel endovascular stents (Wallstent) in the native coronary arteries (94 stents) or saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were obtained immediately before and after placement of the stent and at follow-up at least one month later (unless symptoms required angiography sooner). The mortality after one year was 7.6 percent (8 patients). Follow-up angiograms (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with 105 stents and were analyzed quantitatively by a computer-assisted system of cardiovascular angiographic analysis. The 10 patients without follow-up angiograms included 4 who died. RESULTS Complete occlusion occurred in 27 stents in 25 patients (24 percent); 21 occlusions were documented within the first 14 days after implantation. Overall, immediately after placement of the stent there was a significant increase in the minimal luminal diameter and a significant decrease in the percentage of the diameter with stenosis (changing from a mean [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10 percent, respectively; P less than 0.0001). Later, however, there was a significant decrease in the minimal luminal diameter and a significant increase in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34 percent at follow-up). Significant restenosis, as indicated by a reduction of 0.72 mm in the minimal luminal diameter or by an increase in the percentage of stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14 percent of patent stents, respectively. CONCLUSIONS Early occlusion remains an important limitation of this coronary-artery stent. Even when the early effects are beneficial, there are frequently late occlusions or restenosis. The place of this form of treatment for coronary artery disease remains to be determined.

Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy

Although attempts have been made to treat hypertrophic obstructive cardiomyopathy with right ventricular pacing, the usual treatment for those refractory to medical therapy is open heart surgery. To assess in detail the value of non-surgical therapy the effects of acute and long-term dual-chamber pacing were investigated in 13 patients with hypertrophic obstructive cardiomyopathy refractory to medical treatment. In the first part of the study, atrioventricular (AV) sequential pacing was found to reduce peak subaortic pressure gradient in 12 of the 13 patients, from 82 (SD 42) to 47 (34) mm Hg (p less than 0.002), without concomitantly reducing aortic blood pressure or cardiac output. This effect was related to AV interval. In the second part of the study, a dual-chamber pacemaker was implanted in 8 patients and programmed to the optimum AV interval for the individual (50-90 ms). Patients were followed up for up to 62 months. Pacing resulted in a significant and long-lasting reduction in severity of angina pectoris (from NYHA class 3 to 1) and dyspnoea (from NYHA class 3 to 2). Echocardiography showed no significant change in septal thickness or left ventricular contractility but there was a trend to a spontaneous decrease in obstruction. In patients with hypertrophic obstructive cardiomyopathy, synchronised and ventricular pacing at optimum AV interval for the individual reduces the intraventricular pressure gradient and improves functional tolerance. Since the effect is longlasting, such pacing should be deemed an alternative therapy to surgery in selected cases.

Emergency stenting for acute occlusion after coronary balloon angioplasty.

Acute coronary artery occlusion complicates 2-12% of the balloon angioplasty procedures, and despite repeat angioplasty, emergency surgical revascularization is often necessary. We report our initial experience with the emergency implantation of endoluminal stents for acute vessel closure after coronary balloon angioplasty. Nine patients received one stent, and two patients received two stents during the study period. Implantation was technically successful in all patients; there were no deaths, no myocardial infarctions as evidenced by Q wave on the electrocardiogram, and no need for emergency surgery. One additional patient, not satisfying the study inclusion criteria, died 16 hours after stent implantation from left ventricular failure and intractable arrythmias. Two patients in the study group had a moderate creatinine phosphokinase rise during the first 48 hours after implantation. During a median follow-up period of 3 months (range, 1-20 months), there have been no deaths and no need for elective coronary bypass surgery. One patient required emergency recanalization 3 months after implantation because of acute occlusion of the stented segment with limited myocardial infarction. Six patients have undergone control angiography, and none has developed chronic restenosis within the stented segment. For selected patients, coronary artery stenting appears to be a promising alternative to emergency bypass surgery after acute vessel occlusion during balloon angioplasty.

Multicenter low energy transvenous atrial defibrillation (XAD) trial results in different subsets of atrial fibrillation

OBJECTIVES This prospective, multicenter trial was aimed at defining efficacy and safety of low energy shocks during atrial fibrillation in a diverse cohort of patients. BACKGROUND Experimental studies in sheep and preliminary data in humans have suggested that low energy internal shocks delivered between right atrial and coronary sinus electrode catheters may terminate atrial fibrillation. METHODS Biphasic 3/3-ms R wave synchronous shocks were delivered between two electrode catheters in the right atrium and coronary sinus. The defibrillation protocol started with a test shock of 20 V, and shocks increased in 40-V steps until restoration of sinus rhythm or a maximum of 400 V. Shock delivery was withheld after short RR intervals. In 141 patients with atrial fibrillation, the protocol was carried out under sedation in case the shock was associated with discomfort. The atrial arrhythmia was paroxysmal (< or = 7 days) in 50 patients, chronic (> 30 days) in 53, intermediate (> 7 days, < or = 30 days) in 18 and induced in 20. Underlying heart disease was present in 88 patients (62%). RESULTS Paroxysmal atrial fibrillation was successfully terminated in 46 (92%) of 50 patients, chronic atrial fibrillation in 37 (70%) of 53, intermediate in 16 (89%) of 18 and induced in 16 (80%) of 20. Mean conversion threshold was 1.8 J (213 V) in the induced group, 2.0 J (229 V) in the paroxysmal group, 2.8 J (272 V) in the intermediate group and 3.6 J (311 V) in the chronic group. The conversion voltage was significantly (p < 0.001) higher in the chronic group than in the other groups of atrial fibrillation and increased significantly with the duration of atrial fibrillation and with left atrial size (p < 0.05). Of 1,779 R wave synchronized shocks delivered with a mean (+/-SD) preceding RR interval of 676 +/- 149 ms, no ventricular arrhythmia was induced. The latter may occur after unsynchronized shocks. CONCLUSIONS Low energy transvenous shocks in patients with atrial fibrillation are effective and safe, provided that shocks are properly synchronized to R waves with preceding RR intervals that meet appropriate cycle length criteria. This study provides data that may be useful in the development of an implanted atrial defibrillator.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options-a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.

Placebo effect of pacemaker implantation in obstructive hypertrophic cardiomyopathy

This study evaluated a possible placebo effect by pacemaker implantation. The study design was a 3-month multicenter, double-blind, randomized cross-over study to compare the effects of atrioventricular (AV) synchronous pacing with an optimal AV delay to inactive pacing in patients with obstructive hypertrophic cardiomyopathy (HC). Quality of life and left ventricular (LV) outflow tract obstruction were evaluated after the first study period in 40 patients assigned to inactive pacing. Data were compared with the corresponding results among the 41 subjects assigned to a first study period of active pacing. During inactive pacing, there was a significant improvement in perceived chest pain, dyspnea, and palpitations. Moreover, LV outflow tract gradient decreased from 71 +/- 32 mm Hg to 52 +/- 34 mm Hg (p = 0.04). In patients assigned to active pacing the reduction of the gradient was significantly more pronounced (70 +/- 24 mm Hg to 33 +/- 27 mm Hg; p <0.0001). The difference in gradient reduction between the groups was highly significant (p <0.00001). In the group assigned to active pacing there was also significant improvement in perceived symptoms as well as in alertness, the ability to be self-autonomous, and strenuous physical exercise. The improvements in the latter were significantly greater in those paced actively compared with patients paced inactively, whereas the changes in perceived symptoms did not differ between groups. In conclusion, pacemaker implantation had a placebo effect on objective and subjective parameters in this group of patients with obstructive HC.

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 sees respectively. Repeated measures ANOVA showed that the QRS duration significantly increased with right ventricular apex or right ventricluar 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 simultaneoasly. 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.

Quantitative angiographic follow-up of the coronary Wallstent in native vessels and bypass grafts (European experience — March 1986 to March 1990)

The coronary stent has been investigated as an adjunct to percutaneous transluminal coronary angioplasty to obviate the problems of early occlusion and late restenosis. From March 1986 to March 1990, 265 patients (308 lesions) were implanted with the coronary Wallstent in 6 European centers. For this study, the patients were analyzed according to date of implantation (group 1, March 1986 to January 1988; group 2, February 1988 to March 1990) and vessel type (native arteries versus bypass grafts). Quantitative angiographic follow-up was performed in 82% of the study patients. The early in-hospital occlusion rate in the overall group was 15%. Group 1 patients had a 20% rate in contrast to 12% rate in group 2 (p = not significant [NS]). The early occlusion rate in native vessels and bypass grafts was 19 and 8%, respectively (p = 0.019). Restenosis was determined by 2 criteria (criterion 1, greater than or equal to 0.72 mm loss in minimal luminal diameter from poststent to follow-up; criterion 2, greater than or equal to 50% diameter stenosis at follow-up) within the stent and in the segments immediately proximal and distal to the stent. The restenosis rate with criterion 1 was 43% in the overall group of patients, 35% in group 1 versus 49% in group 2 (p = NS), and 34% in native vessels versus 54% in bypass grafts (p = 0.016). The second criterion was met by 27% of patients in the overall group, 21% in group 1 versus 32% in group 2 (p = NS), and 18% in native vessel versus 39% in bypass grafts (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria.

The maintenance of multiple wavelets appears to be a consistent feature of atrial fibrillation (AF). In this paper, we investigate possible mechanisms of initiation and perpetuation of multiple wavelets in a computer model of AF. We developed a simplified model of human atria that uses an ionic-based membrane model and whose geometry is derived from a segmented magnetic resonance imaging data set. The three-dimensional surface has a realistic size and includes obstacles corresponding to the location of major vessels and valves, but it does not take into account anisotropy. The main advantage of this approach is its ability to simulate long duration arrhythmias (up to 40 s). Clinically relevant initiation protocols, such as single-site burst pacing, were used. The dynamics of simulated AF were investigated in models with different action potential durations and restitution properties, controlled by the conductance of the slow inward current in a modified Luo-Rudy model. The simulation studies show that (1) single-site burst pacing protocol can be used to induce wave breaks even in tissue with uniform membrane properties, (2) the restitution-based wave breaks in an atrial model with realistic size and conduction velocities are transient, and (3) a significant reduction in action potential duration (even with apparently flat restitution) increases the duration of AF. (c) 2002 American Institute of Physics.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.