Gleichmann U

Nonsurgical Septal Reduction for Hypertrophic Obstructive Cardiomyopathy Outcome in the First Series of Patients

BACKGROUND Some patients with hypertrophic obstructive cardiomyopathy may gain symptomatic relief from a reduction in the extent of obstruction to left ventricular outflow. We present the outcome of the first series of patients treated with an alternative method of gradient reduction using catheter techniques. METHODS AND RESULTS Eighteen patients were treated with selective intracoronary alcohol injection to induce localized septal infarction. Patients underwent echocardiographic measurement of left ventricular dimensions and Doppler echocardiographic evaluation of left ventricular outflow tract gradients before the procedure, on the first postoperative day, and at a median follow-up of 3 months after the procedure. In addition, patients underwent exercise testing and symptom evaluation before and 3 months after nonsurgical septal reduction. There was a significant reduction in left ventricular outflow tract obstruction after the procedure (preprocedure, 67 mm Hg [95% CI, 48 to 87 mm Hg]; postprocedure, 25 mm Hg [95% CI, 16 to 34 mm Hg]; P=.0006), which persisted at 3-month follow-up (22 mm Hg [95% CI, 12 to 32 mm Hg]; P=.001). This was associated with a significant improvement in symptoms. There was a small but not significant increase in exercise capacity (n=10; preprocedure, 418 seconds [95% CI, 273 to 563 seconds]; postprocedure, 452 seconds [95% CI, 283 to 621 seconds). Left ventricular dimensions were not significantly altered by nonsurgical septal reduction. CONCLUSIONS Nonsurgical septal reduction significantly reduces left ventricular outflow tract obstruction and improves symptoms in some patients with hypertrophic obstructive cardiomyopathy. The technique may provide an alternative to surgical myomectomy in selected patients.

Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy Results With Respect to Intraprocedural Myocardial Contrast Echocardiography

BACKGROUND Percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative procedure for reducing the left ventricular outflow tract gradient (LVOTG) in hypertrophic obstructive cardiomyopathy. We report on the acute and mid-term results in 91 symptomatic patients with respect to intraprocedural myocardial contrast echocardiography (MCE). METHODS AND RESULTS PTSMA was intended for 46 women and 45 men (54.1+/-15.5 years). In 2 patients, the intervention could not be completed. In the first 30 patients the target vessel was determined by probatory balloon occlusion alone and in the remainder by additional intraprocedural MCE. Resting LVOTG was reduced from 73.8+/-35.4 to 16.6+/-18.1 and nostextrasystolic LVOTG from 149.3+/-42.5 to 61. 9+/-43.0 mm Hg (P<0.0001 each). In 10 (11%) patients, permanent DDD pacemaker implantation was necessary. Two (2%) patients died, 1 from ventricular fibrillation associated with treatment for chronic obstructive pulmonary disease after 9 days and 1 from fulminant pulmonary embolism after 2 days. After 3 months, mean New York Heart Association class was reduced from 2.8+/-0.6 to 1.1+/-1.0 (P<0.0001). The LVOTG remained reduced to 14.6+/-25.5 mm Hg at rest and 49. 1+/-48.7 mm Hg (P<0.0001 each). Four patients underwent successful repeat PTSMA. Determination of the target vessel by MCE was associated with a higher rate of acute (92% vs 70%; P<0.01) and mid-term (94% vs 64%; P<0.01) success. CONCLUSIONS PTSMA is a promising nonsurgical technique for reduction of symptoms and LVOTG in hypertrophic obstructive cardiomyopathy. MCE has been shown to be a useful addition to probatory balloon occlusion for target vessel selection. Prospective, long-term observations of larger populations and a comparison with the established forms of therapy are necessary to determine the definitive significance of PTSMA.

Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and 3-month follow-up in 25 patients.

OBJECTIVES We report the acute results and midterm clinical course after percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND In the treatment of HOCM, surgical myectomy and DDD pacemaker therapy are considered the standard procedural extensions to drug therapy with negatively inotropic drugs. As an alternative nonsurgical procedure for reducing the left ventricular outflow tract (LVOT) gradient, PTSMA by alcohol-induced septal branch occlusion was introduced. However, clinical follow-up has not been sufficiently described. METHODS In 25 patients (13 women, 12 men; mean [+/- SD] age 54.7 +/- 15.0 years) who were symptomatic despite sufficient drug therapy, 1.4 +/- 0.6 septal branches were occluded with an injection of 4.1 +/- 2.6 ml of alcohol (96%) to ablate the hypertrophied interventricular septum. After 3-months, follow-up results of LVOT gradients and clinical course were determined. RESULTS The invasively determined LVOT gradients could be reduced in 22 patients (88%), with a mean reduction from 61.8 +/- 29.8 mm Hg (range 4 to 152) to 19.4 +/- 20.8 mm Hg (range 0 to 74) at rest (p < 0.0001) and from 141.4 +/- 45.3 mm Hg (range 76 to 240) to 61.1 +/- 40.1 mm Hg (range 0 to 135) after extrasystole. All patients had angina pectoris for 24 h. The maximal creatine kinase increase was 780 +/- 436 U/liter (range 305 to 1,810) after 11.1 +/- 6.0 h (range 4 to 24). Thirteen patients (52%) developed a trifascicular block for 5 min to 8 days requiring temporary (n = 8 [32%]) or permanent (DDD) pacemaker implantation (n = 5 [20%]). An 86-year old woman died 8 days after successful intervention of uncontrollable ventricular fibrillation in conjunction with beta-sympathomimetics in chronically obstructive pulmonary disease. The remaining patients were discharged after 11.3 +/- 5.4 days (range 5 to 24), after an uncomplicated hospital course. Clinical and echocardiographic follow-up was achieved in all 24 surviving patients after 3 months. No cardiac complications occurred. Twenty-one patients (88%) showed clinical improvement, with a New York Heart Association functional class of 1.4 +/- 1.1. A further reduction in LVOT gradient was shown in 14 patients (58%). CONCLUSIONS PTSMA of HOCM is a promising nonsurgical technique for septal myocardial reduction, with a consecutive reduction in LVOT gradient. Possible complications are trifascicular blocks, requiring permanent pacemaker implantation, and tachycardiac rhythm disturbances. Clinical long-term observations of larger patient series and a comparison with conventional forms of therapy are necessary to determine the conclusive therapeutic significance.

Improvement of coronary vasodilatation capacity through single LDL apheresis

A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.

Intraprocedural myocardial contrast echocardiography as a routine procedure in percutaneous transluminal septal myocardial ablation: Detection of threatening myocardial necrosis distant from the septal target area

Percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative to surgery for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). Visualization of the ablation area prior to induction of the chemical necrosis is possible by intraprocedural myocardial contrast echocardiography (MCE). We report on two patients in whom MCE showed opacification of the medial papillary muscle or the left ventricular posterolateral free wall. In both patients the correct ablation area could be identified by MCE after a change of the target vessel, thus avoiding potentially fatal complications due to induction of a necrosis of myocardium distant from the septal target area. Cathet. Cardiovasc. Intervent. 47:462–466, 1999.

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Vorhersage des Risikos permanenter atrioventrikulärer Überleitungsstörungen nach perkutaner Septumablation bei Patienten mit hypertropher obstruktiver Kardiomyopathie

Background and introduction: Damage to the AV conduction system is a frequent complication of percutaneous septal ablation (PTSMA) that needs early and reliable identification of those patients (pts.) at risk for complete heart block (CHB) and subsequent pacemaker implantation. Methods and results: In the first 39 pts. who underwent PTSMA in 1996, AV conduction recovery needed up to 11 days. One pt. suffered from unexpected CHB after 9 days. Seven pts. who needed a DDD pacemaker (DDD-PM) were compared to those without conduction disturbances. A score was established which identified all DDD-PM candidates retrospectively if they presented with >12 score points. In the following 137 consecutive pts. treated in 1997 and 1998, this score was applied prospectively, and again correctly identified all candidates for a DDD-PM. In addition, a low risk group was identified with <8 score points. From 1999 on, the score was applied in routine clinical decision-making in 120 consecutive pts. with respect to DDD-PM implantation. All low risk pts. (<8 points) remained free from bradycardias, while 2/54 pts. (4%) of the intermediate risk group, and 20/23 pts. (87%) of the high risk group had to undergo DDD-PM implantation. Pts. with a first-degree AV block or those with a right bundle branch block at baseline had no excess risk, while 50% of the pts. with a left bundle branch block (LBBB) needed a DDD-PM. Conclusions: Based on pre-interventional data and careful monitoring of the first 48 hours after PTSMA, identification of pts. at risk for CHB and subsequent DDD-PM implantation seems to be possible. Pts. with a score <8 seem to be at low, those with >12 points at high risk. In the remaining cases watchful waiting with prolonged monitoring may allow AV conduction to recover, thus, reducing the number of unnecessary DDD-PM implantations. In cases with LBBB at baseline, however, implantation of a DDD-PM should be considered first-line therapy. Einleitung: Höhergradige AV-Überleitungsstörungen (AVB) stellen eine häufige Komplikation der perkutanen Septumablation (PTSMA) dar und erfordern eine frühzeitige und verlässliche Identifikation derjenigen Patienten (Pat.), die einen permanenten DDD-Schrittmacher (DDD-SM) benötigen. Methoden und Ergebnisse: Wir beobachteten den Spontanverlauf des AVB bei den ersten 39 im Jahr 1996 mittels PTSMA behandelten Pat., ausgenommen 6 Pat. mit bereits implantiertem DDD-SM bzw. vorbestehenden Erregungsleitungsstörungen, wobei die stabile Erholung einer gestörten Überleitung maximal 11 Tage benötigte. Sieben der verbleibenden 33 Pat. erhielten einen DDD-SM. Der Vergleich dieser Pat. mit denen ohne AVB resultierte in einem Scoresystem, welches mit >12 Punkten retrospektiv alle DDD-SM-Kandidaten identifizierte. Bei den 137 nachfolgenden Pat. der Jahrgänge 1997 und 1998 wurde dieser Score prospektiv angewendet und klassifizierte ebenfalls alle weiteren DDD-SM-Kandidaten korrekt. Darüber hinaus konnte eine Gruppe niedrigen Risikos mit <8 Score-Punkten ermittelt werden. Ab dem Jahr 1999 an erfolgte die Anwendung des Score-Systems bei 120 konsekutiven Pat. in der klinischen Routine. In der Niedrig-Risikogruppe (<8 Punkte) blieben sämtliche Pat. ereignisfrei. Ein DDD-SM war bei 2/52 (4%) der Gruppe mit mittlerem Risiko, und bei 20/23 (87%) der Hochrisikogruppe erforderlich. Ein AV-Block Grad I oder ein Rechtsschenkelblock im Ausgangs-EKG vor PTSMA erhöhte die Wahrscheinlichkeit einer DDD-SM-Implantation nicht, während Pat. mit Linksschenkelblock (LSB) eine Schrittmacher-Quote von 50% aufwiesen. Schlussfolgerung: Basierend auf der Kombination präinterventioneller Daten mit einer sorgfältigen Überwachung der ersten 48 h nach PTSMA erscheint die zuverlässige Identifikation von DDD-SM-Kandidaten möglich. Patienten mit <8 Punkten des vorgestellten Score haben ein äußerst geringes, solche mit >12 Punkten ein sehr hohes Risiko für einen permanenten AVB. In den verbleibenden Fällen kann unter prolongiertem Monitoring die Erholung der AV-Überleitung abgewartet und so die Zahl langfristig unnötiger DDD-SM-Implantationen verringert werden. Bei Pat. mit LSB erscheint die primäre Versorgung mit einem DDD-SM sinnvoll.

Evidence against heterozygous coagulation factor V 1691 G→A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction

The aim of our study was to determine the prevalence of the factor V mutation (position 1691 G→A) in patients with angiographically diagnosed coronary artery disease and myocardial infarction and, as a control, in blood donors. This mutation has already been proved to be the main genetic risk factor for venous thrombosis. In order to detect this mutation in exon 10 of the factor V gene we established a microtiter plate based hybridization assay for the specific detection of wild-type and mutant sequences in factor V gene segments, obtained after amplification by polymerase chain reaction. This test enables us to screen a large number of samples. The mutation was detected in 29 of 317 coronary artery disease (CAD) patients (9.1%) and 18 of 190 blood donors (9.5%) investigated. The mean activated protein C resistance ratios were 3.18 and 3.11, with nearly identical distribution. No increased prevalence of the factor V mutation was found in the CAD group. In 10 of 29 CAD patients (35%) with the factor V 1691 G→A mutation and in 124 of 288 CAD patients without the mutation (43%) there was a history of myocardial infarction. From our data we conclude that there is no increased risk of developing coronary atheroma or consecutive myocardial infarction resulting from the factor V mutation with protein C resistance.

Perkutane transluminale septale Myokardablation bei hypertroph-obstruktiver Kardiomyopathie: Akutergebnisse bei 66 Patienten unter Berücksichtigung der Myokard-Kontrastechkardiographie

Background: In hypertrophic obstructive cardiomyopathy (HOCM) therapy, surgical myectomy and DDD pacemaker implantation are considered to be established extensions to medical treatment. As an alternative procedure for reducing the left ventricular outflow track gradient (LVOTG), percutaneous transluminal septal myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion has been introduced. We report on the acute results and the short-term clinical course following 66 PTSMA interventions in symptomatic patients (pts.) with HOCM. Methods: In pts. who were symptomatic despite adequate drug therapy (31 women, 35 men; mean age 52.9 ± 15.0 years, range: 16–86) 66 PTSMA interventions were performed (4 pts. with a re-intervention). Septal branches were included by injection of 3.5±1.8 (1.5–11.0) ml ethanol (96%). In the first 30 pts. the target vessel was determined by probatory balloon occlusion (PBO) alone, in the following 36 by additional myocardial contrast echocardiography (MCE). In-hospital follow-up of LVOTG and clinical course were determined. Reults: The invasively determined LVOTG could be reduced by > 50% or eliminated in 54 interventions (82%) with a mean reduction from 71.2 ± 34.4 (4–174) to 18.0 ± 21.5 (0–105) mm Hg at rest and from 145.7 ± 42.3 (68–257) to 63.7 ± 49.3 (0–185) mm Hg post extrasystole (p < 0.0001). All pts. experienced angina pectoris with the first 24 hours. The creatine kinase peak was 690 ± 364 (201–1810) U/l after 11.0 ± 5.4 (4–24) hours. 45 pts. (68%) developed trifascicular block, requiring temporary, or in 9 cases (14%) permanent, (DDD) pacemaker implantation. Two pts. (3%) died 9 and 2 days after a successful intervention, due to uncontrollable ventricular fibrillation associated with betasympathomimetic and theophylline treatment for chronic obstructive pulmonary disease in one case, and fulminant pulmonary embolism in the other. The remaining pts. were discharged after 11.1 ± 4.6 (5–24) days, following an uncomplicated hospital course. The introduction of MCE was associated with a higher percentage of short-term success (92% vs. 70%, p < 0.015. Conclusion: PTSMA in HOCM is a promising non-surgical technique for septal myocardial reduction with a consecutive reduction of the LVOTG. MCE has shown to be a useful addition to PBO for selection of the target vessel. Possible complications are trifascicular blocks requiring permanent pacemaker implantation and tachycardiac rhythm disturbances. Prospective long-term observations of larger populations and a comparison with the established forms of therapy are necessary in order to determine the definitive significance of PTSMA. Hintergrund: Die chirurgische Myotomie-Myektomie und die DDD-Schrittmacherimplantation gelten als Therapieoptionen für medikamentös nicht hinreichend behandelbare Patienten (Pat.) mit hypertroph-obstruktiver Kardiomyopathie (HOCM). Als alternative nichtchirurgische Strategie wurde die perkutane transluminale septale Myokardablation (PTSMA) zur Reduktion der septalen Hypertrophie bzw. des Gradienten über dem linksventrikulären Ausflußtrakt (LVOTG) entwickelt. Wir berichten über Akutergebnisse und Hospitalverlauf der ersten 66 Patienten. Methoden: Bei 66 trotz Medikation symptomatischen Patienten (4 Pat. mit 2 Interventionen; 31 Frauen, 35 Männer; mittleren Alters 52,9& plusmn; 15,0 (16–86 Jahre) mit HOCM wurde die Indikation zur PTSMA gestellt. Die Intervention erfolgte durch Injektion von 3,5 ± 1,8 (1,5–11) ml 96%igen Alkohols. Bei den ersten 30 Interventionen wurde das Zielgefäß durch probatorische Ballonokklusion (PBO) ermittelt, bei den folgenden Eingriffen mittels zusätzlicher Myokard-Kontrastechokardiographie (MCE). Das hämodynamische Akutergebnis und der klinische Verlauf wurden erfaßt. Ergebnisse: Die invasiv gemessenen LVOTG konnten bei 54 Interventionen (82%) um mehr als 50% gesenkt oder ganz beseitigt werden mit einer Reduktion von im Mittel 71,2 ± 34,4 (4–174) auf 18,0 ± 21,5 (0–105) mm Hg in Ruhe bzw. von 145,7 ± 42,3 (68–257) auf 63,7 ± 49,3 (0–185) mm Hg postextrasystolisch (p < 0,0001). Alle Patienten klagten über mäßige, pektanginöse Beschwerden. Der CK-Gipfel betrug 690 ± 364 (201–1810) U/l nach 11,0 ± 5,4 (4–24) h. Ein trifaszikulärer Block entwickelte sich nach 45 Eingriffen (68%); in 9 Fällen (14%) mußte ein permanenter DDD-Schrittmacher implantiert werden. Zwei Patienten (3%) verstarben 9 bzw. 2 Tage nach primär effektiver PTSMA infolge intraktablen Kammerflimmerns, assoziiert mit einer beta-mimetischen und Theophyllin-Therapie wg. schwerer chronischer obstruktiver Atemwegserkrankung (COLD) in einem und an einer fulminanten Lungenembolie im zweiten Fall. Die übrigen Patienten wurden nach 11,1 ± 4,6 (5–24) die bzw. unauffälligem Hospitalverlauf entlassen. Die Einführung der MCE war mit einer höheren Rate akut erfolgreicher Eingriffe assoziiert (92% vs. 70%, p < 0,015). Schlußfolgerung: Die PTSMA ist eine vielversprechende Option für medikamentös nicht hinreichend behandelbare Patienten mit HOCM. Zur Auswahl des Zielgefäßes hat sich die MCE als Zusatz zur PBO als hilfreich erwiesen. Komplikationsmöglichkeiten sind vor allem bradykarde (aufgrund einer permanenten trifaszikulären Blockierung mit der Notwendigkeit der DDD-Schrittmacher-Implantation) Rhythmusprobleme. Langzeitbeobachtungen, möglichst in Form eines prospektiv angelegten Registers und bei größeren Patientengruppen, sind notwendig zur Definition des Stellenwerts im Vergleich zu den etablierten Behandlungsverfahren.

Results of Heart Transplantation in Patients with Preexisting Malignancies

Twenty patients with end-stage heart failure and preexisting malignancies underwent heart transplantation at a single center, with a neoplasm-free interval before the procedure of 0 to 240 months. Twelve patients were long-term survivors (2 to 72 months); there were 2 early and 6 late deaths, thus justifying heart transplantation in patients with preexisting malignancies in individual cases.