Christian Weinhold

Detection of acute phase response and infection. The role of procalcitonin and C-reactive protein.

Abstract Objective: Established parameters, e.g. C-reactive protein (CRP), do not differentiate specifically enough between patients developing an infection and those exhibiting an acute phase response following cardiac surgery. The objective of this prospecitive study was to investigate if procalcitonin (PCT) ist more helpful than CRP. Methods: During a 1-year period, seven out of 563 patients (1.2 %) developed systemic infections (group A) after cardiac operations with cardiopulmonary bypass (CPB), and additional eight patients (1.4 %) had local wound infections requiring surgical therapy (group B). Blood samples for PCT and CRP measurements were taken preoperatively, at the onset of infection (d1), as well as on the third day (d3), fifth day (d5), and seventh day (d7) following diagnosis of infection. Forty-four randomly selected patients undergoing cardiac surgery with CPB without clinical signs of infection, additional intensive care unit (ICU) management or additional antibiotic treatment served as control (group C) to assess the PCT and CRP contribution to acute phase response. PCT and CRP levels were measured preoperatively, on the first (d1), third (d3) and fifth day (d5) after operation. Results: At the onset of infection, PCT levels (median interquartile range 25 %–75 %) increased significantly in group A as compared to baseline values (10.86 (3.28–15.13) ng/ml vs. 0.12 (0.08–0.21) ng/ml), and decreased during treatment to still significantly elevated values on d5 (0.56 (0.51–0.85) ng/ml). CRP levels were significantly elevated on all days investigated with no trend towards normalisation (d1: 164.5 (137–223) mg/l) vs. 1.95 (1.1–2.8) mg/l preoperatively, d5: 181.1 (134–189.6) mg/l. In group B, no increase in PCT levels, but a significant increase of CRP from d1 (165.9 (96.6–181.6) mg/l) vs. 3.7 (2–4.3) mg/l preopratively) until d5 98 (92.8–226.2) mg/l was detected. In group C, postoperative PCT levels increased slightly but significantly in the absence of infection on d1 (0.46 (0.26–0.77) ng/ml vs. 0.13 (0.08–0.19) ng/ml preoperatively), and d3 (0.37 (0.2–0.65) ng/ml and reached baseline on d5 (0.24 (0.11–0.51) ng/ml)). CRP levels were significantly elevated as compared to baseline on all postoperative days investigated (baseline: 1.75 (0.6–2.9) mg/l, d1: 97.5 (74.5–120) mg/l), d3: 114 (83.05–168.5) mg/l, d5: 51.4 (27.4–99.8) mg/l)). PCT showed a significant correlation to CRP in group A (r = 0.48, p < 0.001), a weak correlation in group C (r = 0.27, p = 0.002) and no correlation in group B. Intergroup comparison revealed a significant difference for PCT between all groups (A > C >B) and significantly higher CRP levels in group A vs. C and in group B vs. C. Thus, the pattern high PCT/high CRP appears to indicate a systemic infection, while low PCT/high CRP indicates either acute phase response or local wound problems, but no systemic infection. The cost for PCT measurements was 5.6-fold higher as compared to CRP. Conclusion: Due to the significant differences in the degree of increase, PCT appears to be useful in discriminating between acute phase response following cardiac surgery with CPB or local problems and systemic infections, with additional CRP-measurement increasing the specifity.

What Is the Most Appropriate Stimulation Mode in Patients with Sinus Node Dysfunction

Sinus node disease (SND) has caused many controversies about the appropriate stimulation mode. We compared the advantages and disadvantages of VVI, AAI, DDD, and DDI mode. In an additional study, left ventricular function at rest [R] and during exercise [E] was investigated in dual chamber and ventricular stimulation mode with a stimulation rate of 70 ppm [R] and 110 ppm [E]. A total of 223 patients [pts] was investigated (67 AAI, 87 VVI, 69 DDI]. Hemodynamic disadvantages in VVI mode resulted in a 55% actuarial incidence of atrial fibrillation after five years. In AAI mode, we found another 25% complication rate due to impaired AV conduction [n = 9] or a bradyarrhythmia [n = 6] with slow ventricular response. DDD mode implies the possibility of sustaining a pacemaker mediated tachycardia. Single ventricular stimulation with a high stimulation rate (110 ppm] under E showed a worse left ventricular performance as compared to dual chamber stimulation. DDI mode shows none of the aforementioned disadvantages. To sum it up: Until a dual chamber rate responsive pacemaker becomes available, the DDI mode represents the best stimulation mode for patients with a SND.

Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions

Cardiac surgery with cardiopulmonary bypass (CPB) is known to induce an immune response whose nature has been increasingly elucidated during the recent decade. Clinically, patients usually show two to three of the four symptoms, which define the so-called systemic inflammatory response syndrome (SIRS). In addition, all parameters of the innate, nonspecific immune system, e.g., polymorphonuclear cells, elastase, and complement, are activated. This also applies to the proinflammatory mediators interleukin (IL)-1beta, -6, and -8, and tumor necrosis factor (TNF)-alpha. Within the adaptive, specific immune system, a decrease of T lymphocytes and T helper (TH) cells is observed, whereas suppressor/ cytotoxic T cells and B cells appear to be nearly unaffected. Cytokine measurements provide more detailed information: IL-2 and IL-12, which are important for the activation of the type-1 TH-cell (TH1)-mediated immune response, are depressed following cardiac operation. In contrast, IL-10 and transforming growth factor-beta essential to TH2-mediated humoral or anti-inflammatory immune response, are upregulated. In vivo tests, e.g., delayed type hypersensitivity skin reaction and tetanus antibody production, confirm the polarization of the adaptive immune response towards the TH2 pathway. However, all these alterations usually do not result in clinical adverse events. Therefore, more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response. For this purpose, more readily available, standardized methods for immunologic monitoring appear highly desirable.

Reliability of Atrial Screw-in Leads

The aim of this study was to investigate long‐term performance of a carbon coated atrial screw‐in lead. During implantation of 247 leads of this type we measured an average stimulation threshold of 0.74 V(range: 0.2–1.6 V) at 1 ms pulse width. Mean lead impedance came to 446 ohms (range: 263–1000 ohms) resulting in an arithmetical energy consumption of 1.51 μJ(range: 0.1–7.21 μJ). Average P wave amplitude was 3.9 mV (range: 1.3–11 mV). After a mean follow‐up of 16.4 months (range; 3–60 months) we found excellent threshold results in 76% of the patients permitting a safety programming al half of nominal value. An additional 14% nominal settings could be retained. With regard to chronic lead impedance of 488 ohms (range: 315–1327 ohms) we calculated an average chronic energy consumption of 10.83 μJ (range: 1.62–22.78 μJ) during safety programming. This made up 34.6% of the corresponding energy consumption during nominal programming. Eighty percent of the patients showed chronic P waves above 2 mV; nearly half of them (n ‐ 94 = 38%) showed a proper sensing function even when programmed to minimal sensitivity settings or above 4 mV. In 19 leads (8%) we observed unsatisfying threshold results requiring high output programmings. All threshold increases occurred within the first year, 84% (n = 16/19) within the first 3 postoperative months. An additional five leads (2%) were found to have a loss of capture, and one (0.5%) a loss of sensing. These complications required reoperation as well as one dislocation (0.5%) resulting in a low complication rate of 3% as compared to the total complication rate of all implanted atrial leads which was substantially higher (n = 48/652 = 7.5%). With regard to our results we consider the carbon coated atrial screw‐in lead to have proven long‐term reliability.

Complications in Dual Chamber Pacing: A Six-Year Experience

In a six‐year period (1980–1985), 345 dual chamber pacing systems were implanted in our hospital. Intraoperative complications were rare (n = 5/345 = 1.4%). 25 patients (7%) have died, 11 (3%) were lost follow‐up. A total of 39 patients (13%) showed minor problems, which could be overcome by reprogramming. Another 48 complications (15%) required reoperation. Nearly 70% of those reoperations (n = 31/48) were caused by a malfunction of the atrial lead. This high complication rate of 9% related to all implanted atrial leads could be reduced in the last three years to 2%. We could maintain a dual chamber stimulation mode (DDD, DDI, DVI, VDD) in 396 patients (99%). We conclude that improvements in lead design, pulse generators programmability, and surgical experience have reduced complication rates to acceptable low values. Meanwhile, dual chamber pacing con be considered as safe as single chamber pacemaker therapy.

One-incision approach for insertion of implantable cardioverter defibrillators

The placement of a transvenous implantable cardioverter defibrillator (ICD) system through a single infraclavicular skin incision has been a surgical goal for years. The development of a new investigational model of ICD with substantially reduced dimensions (volume, 83 cm3; mass, 132 g) has made the one-incision approach a clinical reality. Between March and September 1993, 4 female and 19 male patients (mean age, 60 +/- 9.6 years; range, 46 to 73 years) underwent implantation of this device for the treatment of ventricular fibrillation (n = 14) or ventricular tachycardia (n = 9). One transvenous lead was placed in the right ventricular apex and another in the left subclavian vein. A subpectoral pocket was formed in the infraclavicular area from the same incision to house the ICD generator and, if necessary, the subcutaneous patch. The mean operation time (81.5 +/- 32.7 minutes; range, 54 to 195 minutes) was significantly shorter than that noted for a previous series made up of patients undergoing traditional transvenous ICD implantations. In 20 patients (87%), endovenous defibrillation without a subcutaneous patch successfully caused externally induced ventricular fibrillation to revert with a mean minimum energy output of 21.9 +/- 3.5 J (range, 12 to 24 J). Endovenous defibrillation was more successful when biphasic (n = 16/17 [94%]) shocks rather than monophasic shocks (n = 4/6 [67%]) were used. No mortality, morbidity, or surgical complications were observed. These results indicate that the one-incision approach and the small size of the ICD generator can substantially facilitate ICD implantation and result in a reduction in the surgical trauma, the operation time, and the amount of material implanted.

The left subclavian vein as an alternative site for implantation of the second defibrillation lead.

The optimal placement for the second defibrillation lead in a twolead system has never been addressed. We retrospectively reviewed the data of 33 patients with an average age of 59.2 years (range 41–78 years), predominantly mala (n = 29), who underwent implantation of a cardioverter defibrillator (ICD) for treatment of ventricular tachycardia (n = 19) or ventricular fibrillation (n = 14). In all patients an attempt was made to implant an endovenous ICD device (leads only, no subcutaneous patch). In group I (n = 18) the defibrillation anode, a separate unipolar lead, was placed in the common position, the superior vena cava. In group II (n =15) the lead was placed in the left subclavian vein. At least two consecutive shocks reverting ventricular fibrillation at energies ±24J were required for implantation of the ICD device. All shocks were monophasic. The success rate of endovenous defibrillation was significantly higher in group II than in group I (67% vs 28%, P < 0.05). Thus, it could be demonstrated that the position of the defibrillation anode can influence the defibrillation efficacy in transvenous ICD systems. Prospective randomized trials are needed to investigate the optimal position for the second defibrillation electrode, which may gain increasing importance as soon as dual chamber ICDs become available.

Determinants of dual chamber pulse generators longevity.

The aim of tbis study was to investigate the effect of battery capacity, internal current drain, and stimulation energy on pulse generators longevity, and if battery impedance measurements can reliably predict pulse generators end‐of‐life. For this purpose, the records of 577 patients with a mean age of 65 ± 14 years who had undergone implantation of two different dual chamber pulse generators (PGl: 409; PG2:168) were retro‐spectively reviewed. Battery capacity were 2.3 Ah (PGl) and 3.0 Ah (PG2) while current drain at compara‐ble nominal settings was 20 μA (PGl) and 30 μA (PG2) indicating a higher internal current drain of PG2. After a mean follow‐up of 46 ± 23 months, stimulation energy at reprogrammed output settings was significantly higher in PGl as compared to PG2 (17.1 ± 0.14 J vs 15.5 ± 0.24 f). Three PGl (0.7%) and 12 PG2 (7.1%) (P < 0.01) had to be exchanged after a mean of 77.3 ± 5.3 months (PGl) and 75 ± 13.5 months (PG2) (P = NS) due to end‐of‐life being reached. The difference in battery impedances of PGl and PG2 gained statistical significance 5 years after implantation (1.0 kΩ vs 2.4 ± 6.7 kΩ) preceding the significant difference in PG survival after 6 years (98.7 ± 1.3% vs 90.7 ± 4.8%). These results indicate that internal current drain is the most important determinant of the pulse generators longevity and that battery impedance can reliably predict end‐of‐life. Therefore, the essential information about internal current drain should be available for each pacemaker, since it is required for adequate pulse generator selection. Diagnostic functions of dual chamber pulse generators should include measurement of battery impedance.

Influence of Anodal Electrode Position on Transvenous Defibrillation Efficacy in Humans: A Prospective Randomized Comparison

Nonthoracotomy lead systems for implantable cardioverter defibrillators (ICDs) have reduced operative mortality and morbidity as compared to epicardial lead systems but are usually associated with higher defibrillation thresholds (DFTs). The purpose of this prospective randomized trial was to investigate if the second defibrillation electrode in the left subclavian vein can increase defibrillation efficacy and decrease DFT as compared to the superior vena cava (SVC) position in nonthoracotomy lead systems for ICDs. Seventeen patients (mean age; 49.9 ± 11.3 years, mean ejection fraction; 46.1%± 15.8%) were implanted with an investigational unipolar electrode (Medtronic 13001) used as the defibrillation anode. DFT testing was started in the SVC (n = 10, group A) or the left subclavian vein (n = 7, group B), and repeated in the alternative position starting at the DFT of the initial position. Fifteen patients were eligible for analysis (group A: n = 9, group B: n = 6). With the electrode in the SVC, ventricular fibrillation could be successfully terminated in 9 out of 15 patients (60%). In the left subclavian vein the success rate was 100% (P < 0.01). Mean DFT in the SVC was 13.0 ± 5.2 J and in the left subclavian vein 10.2 ± 4.9 J. DFTs in the left subclavian vein were either lower (group A: n = 5/9, group B: n = 5/6) or equal to the results in the SVC position (P < 0.001). Thus, the left subclavian vein appears to be a superior alternative for positioning of the defibrillation anode as compared to the SVC for nonthoracotomy lead systems using two separate leads.

Comparison of UW versus HTK solution for myocardial protection in heart transplantation.

Abstract In order to evaluate the protective effect of University of Wisconsin (UW) solution in heart transplantation, a retrospective comparative study with histidine‐tryptophane‐ketoglutarate (HTK) solution was initiated. In group I, we included 160 patients with HTK preservation, while group II consisted of 50 patients who had their transplant protected with UW solution. All patients received standard quadruple drug therapy for immunosuppression. The average ischaemic time of the donor hearts in group I was 142 ± 44 min, ranging from 83 to 235 min. Acute immediate perioperative graft failure occurred in six cases (3.8YO). Statistical analysis including the chi‐quare test, revealed a significant increase in the incidence of acute perioperative graft failure when compared with duration of ischaemic time (P < 0.01). Within the first 30 postoperative days, 24 patients died (15% early mortality). The same statistical correlation was evident between the incidence of early mortality and duration of graft ischaemic time. The 30‐day and 6‐month survival rates were 81% and 78%, respectively. The average ischemic time of the donor hearts in group II was 193 ± 50 min ranging from 100 to 360 min, which was significantly longer in comparison with the group I (P < 0.05). Acute perioperative graft failure occurred once (2%); the patient was retransplanted successfully. Five patients died within the first 30 postoperative days (10% early mortality). There was no correlation between length of ischaemic time and incidence of acute graft failure or early mortality. The 30‐day and 6‐month survival rates were 90% and 88%, respectively and, thus, better when compared with group I. In both groups similar results were achieved with regard to postoperative NYHA status of the patients and incidence of cardiac arrhythmias. Myocardial preservation with HTK solution showed satisfying results as long as the ischaemic time did not exceed 4 h. The early functional results achieved with UW graft protection were excellent, even with ischaemic times longer than 4 h and not depending on lenght of ischaemic period.