Herzschr Elektrophys 17:185–190 (2006) DOI 10.1007/s00399-006-0533-x
ORIGINAL CONTRIBUTION
H. Nägele S. Hashagen M. Azizi S. Behrens M. A. Castel
Long-term hemodynamic benefit of biventricular pacing depending on coronary sinus lead position
Received: 30 October 2006 Accepted: 21 November 2006
Langfristiger Benefit der biventrikulären Stimulation in Abhängigkeit von der Elektrodenposition in den Koronarvenen " Zusammenfassung Einführung Akute Testungen unter biventrikulärer Stimulation zeigten, dass der hämodynamische Effek von der Position der Koronarsinus-(CS)-Elektrode abhängt. Langzeituntersuchungen hierzu liegen jedoch bislang nicht vor. Methoden Bei 45 Patienten (Alter 59 ± 10 Jahre) mit Herzinsuffizienz (17 dilatative Kardiomyopathie, 23 ischämische, 5 valvuläre) und Linksschenkelbock (QRS-Breite > 150 ms) wurden biventrikuläre Schrittmachersysteme implantiert. Die CS-Elektroden wurden posterior (P, n = 15), lateral (L, n = 19) oder bei fehlenden anderen Optionen anterior (A, n = 11) implantiert. Präoperativ und nach 6 Monaten wurden Klinik, BNP, Echokardiographie und Rechtsherzkatheter beurteilt. Ergebnisse Eingangsparameter waren in den 3 Gruppen ähnlich. Nach 6 Monaten fanden sich 32/34 Responder in den Gruppen P und L verglichen mit 7/11 in Gruppe A (94 vs. 64%, p = 0,025). Die Ejektionsfraktion steigerte sich in den Gruppen P und L um 40 und 41% vs. nur 19% in A (p < 0,03 für A vs. P + L). BNP-Spiegel sanken deutlicher in den Gruppen P und L (–55 und –35% vs. –27%, p = 0,05 für A vs. P). Die Hämodynamik verbesserte sich nur in den Gruppen P und L: Arterieller Druck + 8 und 9% vs. + 2%, PCWP –23 und –15% vs. –4%, Pulmonalisdruck –18 und –12% vs. –3% (p < 0,01 für A vs. P + L), Herzindex + 21 und + 12% vs. + 11% (p = 0,03 für A vs. P). Schlussfolgerung Chronische biventrikuläre Stimulation verbessert Klinik, Auswurffraktion, BNP und Hämodynamik bei Patienten mit posteriorer und lateraler CS-Elektrodenposition. Anteriore CS-Elektrodenpositionen sollten vermieden werden.
Dr. Herbert Nägele ()) · S. Hashagen M. Azizi · S. Behrens Gustav-Adolf-Stift 21465 Reinbek, Germany Tel.: +49-40 / 72 80-51 58 Fax: +49-40 / 72 80-27 29 E-Mail:
[email protected] M. A. Castel Hospital Son Llatzer Palma de Mallorca, Spanien
" Schlüsselwörter Kardiale Resynchronisationstherapie – Biventrikuläre Stimulation – Koronarsinus-Elektrodenposition – Hämodynamik – Herzinsuffizienz " Summary Background Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. Methods In 45 heart failure patients with left bundle branch block and QRS > 150 ms (age 59 ± 10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n = 15), lateral (L,
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n = 19) or, if no other option available, anterior (A, n = 11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. Results Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs roups P and L: Arterial pressure + 8 and + 9% vs + 2%; PCWP –23 and –15% vs –4%, pulmonary pressure – 18 and –12% vs –3% (p < 0.01 for A vs P + L); cardiac index + 21 and + 12% vs + 11% (p = 0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p = 0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by + 19% in A (p < 0.03 for A vs P + L). Conclusion Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantely in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided. " Key words Cardiac resynchronization therapy – biventricular pacing – coronary sinus lead position – hemodynamics – heart failure
Introduction An intraventricular conduction delay is present in many patients with heart failure and was identified as an independent risk factor [1]. Recently, it was shown that biventricular pacing (cardiac resynchronization therapy, CRT) in patients with left bundle branch block can improve NYHA functional state, quality of life, exercise capacity, echocardiac parameters including left ventricular ejection fraction, and even prognosis [2, 5, 7, 9]. Central hemodynamics also have been shown to improve during acute testing [8] but until now no data have been published on the hemodynamic long-term effect of CRT which requires repeated right heart catheterization. Morevover, the most critical issue of CRT is positioning of the coronary sinus lead because not every region can be accessed due to variations in coronary vein anatomy [6]. Therefore, it may be speculated that lead position can influence outcome and explain the occurrence of patients not responding to CRT [4]. Therefore it would be of special interest to correlate dif-
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ferent coronary sinus lead positons to hemodynamic changes over time.
Methods n Patients We included patients with left bundle brunch block for CRT from candidates for heart transplantation submitted to our heart failure outpatient clinic. The characteristics of these patients are shown in Table 1. There was no significant difference in baseline characteristics, especially no differences for medical therapy with regard to proportion of patients receiving ACE inhibitors and bblocking agents, nor for the drug doses used. Before implantation medical therapy was adjusted according to recommendations of the European Society of Cardiology [10]. ACE inhibitors were increased to the maximum tolerable dosage; b-blocker application was attempted in every patient with doses increased according to patients’ tolerance.
n Echocardiography Doppler echocardiography was performed in all patients at baseline before device implantation and repeated at the 6-month follow-up visit using an HDI 5000 echocardiography machine (Philips). Left ventricular ejection fraction was calculated according to the Simpson method and left ventricular enddiastolic diameter by conventional parasternal M-Mode measurements. The degree of mitral and tricuspid regurgitation was assessed in orthogonal apical echocardiographic images as the average of the maximal areas of the color flow Doppler regurgitant jet within the left and right atrium, and as the ratio of regurgitant jet area to left and right atrial area. Pulsed Doppler velocity signals of transmitral flow were recorded at 100 mm/s with the sample volume at the tips of the mitral valve leaflets. Peak velocities were measured during early left ventricular filling (E-wave) and atrial contraction (A-wave), and the velocity ratio (E/A) was calculated. The deceleration slope and deceleration time of the E-wave (EDT), left ventricular filling time, and isovolumic relaxation time were measured. Left ventricular ejection fraction and diameter, severity of mitral regurgitation, and measurements of diastolic function were reassessed after 6 months to characterize time-dependent changes.
n Right heart catheterization Before and 6 months after CRT was instituted, all patients underwent right heart catheterization under optimized medical heart failure therapy. This investigation was clinically indicated as most of the patients were candidates for heart transplantation and complete hemodynamic data were required to decide further listing
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Table 1 Baseline characteristics of the patients
Age (years) Male (%) Coronary artery disease (n) Dilated cardiomyopathy (n) Valvular cardiomyopathy (n) Atrial fibrillation (n) NYHA functional class QRS duration (ms) ACE inhibitors/AT1 antagonists b-blocker Diuretics LVEF (%) LVEDD (cm) FS (%) Mitral regurgitation (8) Tricuspid regurgitation (8) E-wave decelaration time (ms) Cardio-thoracic ratio Sodium (mmol/l) Creatinine (mg/dl) Brain natriuretic peptide (pg/ml) Heart rate (bpm) Heart rate at 25 W (bpm) MAP (mmHg) MAP at 25 W (mmHg) RAP (mmHg) RAP at 25 W (mmHg) PAM (mmHg) PAM at 25 W (mmHg) PCWP at rest (mmHg) PCWP at 25 W (mmHg) PVR (dyn) LVSWI (pm) LVSWI at 25 W (pm) AVDO2 (Vol%) AVDO2 at 25 W (Vol%) CI (l/min · kgKG) CI at 25 W (l/min · kgKG)
Posterior N = 15
Lateral N = 19
Anterior N = 11
P
61 ± 6 81% 8/15 6/15 1/15 5/15 3.2 ± 0.3 181 ± 38 15/15 14/15 15/15 24 ± 6 7.0 ± 0.9 17 ± 4 2.1 ± 0.9 1.5 ± 0.9 134 ± 47 0.57 ± 0.07 134 ± 5 1.5 ± 0.4 637 ± 517 65 ± 12 81 ± 16 68 ± 9 75 ± 11 5±6 11 ± 4 26 ± 9 39 ± 12 15 ± 6 26 ± 9 234 ± 188 23 ± 8 24 ± 8 6.1 ± 1.2 11.7 ± 2.2 2.1 ± 0.5 2.9 ± 0.7
61 ± 9 80% 9/19 6/19 4/19 4/19 3.2 ± 0.3 181 ± 28 19/19 17/19 19/19 25 ± 6 6.8 ± 0.7 17 ± 4 1.6 ± 0.9 0.9 ± 0.9 126 ± 60 0.56 ± 0.08 136 ± 5 1.2 ± 0.4 638 ± 517 73 ± 16 89 ± 23 69 ± 13 72 ± 10 6±6 13 ± 4 27 ± 14 39 ± 12 18 ± 9 28 ± 9 202 ± 134 22 ± 8 23 ± 8 6.6 ± 1.2 11.1 ± 2 2.3± 0.5 3.1± 0.7
63 ± 10 79% 6/11 4/11 1/11 5/11 3.1 ± 0.3 177 ± 21 11/11 8/11 11/11 22 ± 12 6.9 ± 1.0 20 ± 8 2.0 ± 0.9 0.9 ± 0.7 146± 30 0.59± 0.07 13 ± 3 1.3 ± 0.6 766 ± 337 69 ± 17 87 ± 17 72 ± 12 76 ± 14 5±3 10 ± 7 32 ± 14 42 ± 12 20 ± 10 26 ± 8 267 ± 169 22 ± 7 26 ± 9 6.6 ± 1.2 11.1 ± 2 2.1 ± 0.5 3.1 ± 0.5
n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s.
ACE angiotensin converting enzyme, AT1 angiotensin 1, AVDO2 arterio-venous oxygen extraction difference, CI cardiac index, FS fraction shortening, LVEDD left ventricular enddiastolic diameter, LVEF left ventricular ejection fraction, LVSWI left ventricular stroke work index, MAP mean arterial pressure, PAM mean pulmonary artery pressure, PCWP pulmonary capillary wedge pressure, PVR pulmonary vascular resistence, RAP right atrial pressure
and other patient management, especially with regard to the pulmonary vascular resistance. The studies were performed under standardized conditions and local anesthesia in the morning at least 60 min after intake of the heart failure drug therapy. A SwanGanz catheter (7F, 4 Lumen, Corodyn-DualthermTM, Braun, Melsungen) was placed in the pulmonary artery unter visual control of the pressure curves (system RECORTM, Philips). Arterial pressures were directely measured by
additional cannulation of radial arteries using a thin Teflon canula (Jelco 20G, Johnson & Johnson). Measurements of cardiac output were performed using thermodilution (system COC, Braun, Melsungen). Measurements were repeated 6 times. Blood gas analysis was performed with an ABL 520 Radiometer Copenhagen (Radiometer, Willich). The following hemodynamic parameters were collected during a complete hemodynamic study at rest and at 25 W exercise:
1. pulmonary artery pressure (mmHg; systolic/diastolic/mean: PAS, PAD, PAM), 2. mean pulmonary capillary wedge pressure (mmHg; PCWP), 3. mean right atrial pressure (mmHg; RAP), 4. systemic arterial pressure (mmHg; systolic/diastolic/ mean: SAP, DAP, MAP), 5. heart rate (HR; bpm), 6. cardiac output (CO; l/min), 7. arterial pH, 8. arterial hemoglobin concentration (g/dl),
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9. arterial partial pressure of oxygen (mmHg), 10. arterial partial pressure of carbon dioxide (mmHg), 11. arterial standard bicarbonate (mmol/l), 12. arterial oxygen saturation (%; minus CO-Hb and Met-Hb), 13. central venous oxygen saturation (%).
ter and a target vein was identified. The first choice was to implant in a posterior or posterolateral side branch, the second choice in an antero-lateral position. If there were no accessible posterior or lateral side branches, an anterior lead position was used.
The following parameters were calculated from the above measurements: 1. stroke volume (SV) = CO/HR, 2. body surface area (BSO) after the formula of Dubois in m2 = body weight · 0.425 [kg] · body height · 0.725 [cm] · 0.0071 [m2/ kg · cm], 3. cardiac index in l/min/m2 = CO/ BSO, 4. pulmonary vascular resistance (PVR) = (PAM–PCWP) · 80 divided by CO (in p · m/cm–5), 5. left ventricular stroke work index (LVSMI in p · m) = (PAM– PCWP · SV · 0.0135) divided by BSO, 6. oxygen content arterial and mixed venous (Ca,v,c) O2; CO2 = (Hb · 1.34) · HbO2 + (PO2 · 0.0031) (ml/100 ml), 7. arterio-venous oxygen extraction difference (AVDO2) = CaO2–CVO2 (ml/100 ml).
n Definition of coronary sinus lead position
n Implantation of CRT systems Pacemaker implantation with coronary sinus leads was performed with standard techniques via left or right cephalic or subclavian veins. The dedicated coronary sinus leads Easytrak 4513 (n = 21, Guidant Inc., MN) and Attain 4193 (n = 24, Medtronic Inc., MN) and pulse generators Contak TR (Guidant Inc.) and InSync III (Medtronic Inc.) were implanted. The right ventricular lead was routinely placed in the right ventricular apex. Intraoperatively, coronary sinus angiography was performed using a balloon cathe-
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Intraoperatively, the lead position was defined using fluoroscopy according to anatomy: Posterolateral side branches arise from the coronary sinus main stem, anterolateral branches from the great cardiac vein directed to the heart margin, and the anterior vein was defined as the final branch of the great cardiac vein in the septal region. Postoperatively the position of the coronary sinus lead was checked by anterior-posterior and lateral X-ray. A posterolateral position was defined as a lead in a posterolateral vein positioned in the posterior third of the radiologic heart shape. An anterolateral position was defined as a lead in an anterolateral vein positioned in the mid third of the radiology heart shape, and an anterior position was defined as a lead positioned in the great cardiac vein in the anterior third of the radiology heart shape.
n Follow-up Early and routine follow-up investigations were performed and included clinical state, physical examination, pacemaker leads measurements, brain natriuretic peptide (BNP) measurements, echocardiography and hemodynamic data. Responders were defined as patients who improved by at least 1 NYHA class [11].
n Statistics Differences in the results were checked for significance by means of Student’s t-test for matched pairs. Differences between groups were tested for significance using variance analysis (ANOVA). All data were expressed as mean ± standard deviation. For these analyses, SPSS for Windows 6.1 was used.
Results Changes between baseline and 6 months are shown in Table 2. There were fewer responders (7/11, 64%) in the group of patients with an anterior coronary sinus lead position as compared to lateral and posterior lead positions where 32/34 patients were responders (94%, p = 0.025 for posterior/lateral vs anterior). Biventricular stimulation shortened QRS width more in the posterior and lateral lead positions but not significantely for anterior lead positions. Patients with a posterior or lateral coronary sinus lead position improved in echocardiographic parameters such as ejection fraction, fractional shortening, or the reduction of AV valve regurgitation. Changes in left ventricular diameter did not show a significant difference after 6 months. For patients with posterior and lateral coronary sinus leads, a significant prolongation of the E wave deceleration time was observed after 6 months, while this did not change in patients with anterior coronary sinus leads. In invasive hemodynamic measurements, an increase in mean arterial pressure could be observed more pronounced in the patients with posterior and lateral leads. Comparably, pulmonary pressures were more effectively improved in these patients, simi-
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Table 2 Hemodynamic changes after 6 months of CRT
Responders QRS duration LVEF LVEDD FS Mitral regurgitation Tricuspid regurgitation E-wave deceleration time Cardio-thoracic ratio Sodium Creatinine Brain natriuretic peptide Heart rate Heart rate 25 W MAP MAP 25 W RAP RAP 25 W (mmHg) PAM (mmHg) PAM 25 W (mmHg) PCWP rest (mmHg) PCWP 25 W (mmHg) PVR LVSWI LVSWI 25 W AVDO2 AVDO2 25 W CI CI 25 W
Posterior N = 15
Lateral N = 19
Anterior N = 11
P
14/15 –11% +40% –6% +38% –40% –40% +50% –7% +2% +5% –55% –5% –10% +8% +13% –2 mmHg +1 mmHg –18% –9% –23% –10% –19% +56% +66% –12% –16% +21% +14%
18/19 –11% +41% –7% +39% –35% –30% +70% –4% –3% +4% –35% –11% –16% +9% +16% –3 mmHg +1 mmHg –12% –6% –15% –14% –8% +66% +68% –10% –4% +12% +2%
7/11 –3% +19% –4% +18% –10% –0% –4% –3% –6% –1% –27% –1% –7% +2% +6% –0 mmHg +3 mmHg –3% –2% –4% +3% +16% +22% +18% –6% +3% +11% –2%
0.025 A vs P & L < 0.01 A vs P & L < 0.01 A vs P & L n.s. < 0.01 P vs A < 0.01 A vs P & L < 0.01 A vs P & L < 0.01 A vs P & L n.s. n.s. n.s. n.s. < 0.01 A vs P & L n.s. < 0.01 A vs P & L < 0.01 L vs A n.s. n.s. < 0.01 A vs P & L < 0.01 P vs A < 0.01 A vs P & L < 0.01 A vs P & L < 0.01 A vs P & L < 0.01 A vs P & L < 0.01 A vs P & L n.s. < 0.01 P vs A n.s. < 0.01 P vs A
For abbreviations see Table 1 and the text (Methods) for further explanation
lar to the arteriovenous oxygen difference and cardiac index. During a mean follow-up of 2.6 ± 0.6 years, there were 6 sudden deaths (2 patients each with posterior, lateral and anterior coronarey sinus leads), no patient died from progression of heart failure or received a heart transplantation.
Discussion In this study in patients with severe heart failure receiving CRT, the 6 month improvement in clinical status, echocardiographic parameters and value derived from right heart catheterization at rest and during 25 W work load depended on the coronary sinus lead position.
Our data of right heart catheterization added results of central hemodynamics to the reported improvements of non-invasive parameters in the follow-up of CRT patients [2, 3, 5]. While there are favorable improvements in groups with coronary sinus leads in the posterolateral and anterolateral position, there are less favorable changes in the group with anterior CS leads. Apart from effects on systolic function as reflected by an increase in ejection fraction and systemic arterial pressures, in particular diastolic function seems to be improved only by anterolateral or posterolateral coronary sinus lead positions, as shown by an increase in E-wave relaxation time only in these patient groups. The augmentation of arterial pressures by CRT has been re-
ported as a beneficial effect of this therapy [3]. This study adds the information that a more pronounced increase of arterial pressure is present at exercise, especially in the patient groups with posterior and lateral lead positions (Table 2). Our findings are correlated to the clinical course where 36% of patients with anterior leads were non-responders compared to only 6% in the other groups. It may be assumed that pacing in regions with the latest activation (i.e., in left bundle branch block the posterolateral wall) seems to provide the greatest chronic hemodynamic benefit. Our findings are in concordance with acute hemodynamic studies showing a greater increase in left ventricular dp/dt in lateral or posterior compared to anterior regions [4].
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However, prognosis in our cohort was not influenced by coronary sinus lead position. It can be concluded that CS lead positioning in the great cardiac vein and the anterior third of the left ventricle (i.e., near the right ventricular pacing lead) reduces efficacy of CRT and should be avoided. If coronary sinus vein anatomy precludes placement in a suitable target vessel, epicardial lead placement may be a better al-
ternative than placing the coronary sinus lead in an anterior branch. However, sudden cardiac death remains the major problem during CRT and may be solved by the addition of prophylactic defibrillation capabilities (ICD). This need was also highlighted by results of the COMPANION trial [3]. Another message from our study is that right heart catheterization can safely be performed in patients with an implanted re-
synchronization device. No lead dislodgements or other side effects were noted. However we recommend X-ray and/or a pacemaker testing after the procedure.
n Limitations This was an observational and not randomized study. Therefore, a selection bias can not be exluded.
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