Thorsten Hanke

Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery

Background: The current study was designed to determine the relation between preoperative cerebral oxygen saturation (Sco2), variables of cardiopulmonary function, mortality, and morbidity in a heterogeneous cohort of cardiac surgery patients. Methods: In this study, 1,178 consecutive patients scheduled for on-pump surgery were prospectively studied. Preoperative Sco2, demographics, N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical outcomes, and 30-day and 1-yr mortality were recorded. Results: Median additive EuroSCORE was 5 (range: 0–19). Thirty-day and 1-yr mortality and major morbidity (at least two major complications and/or a high-dependency unit stay of at least 10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative oxygen supplemented Sco2 (Sco2min-ox) was 64% (range: 15–92%). Sco2min-ox was correlated (all: P value <0.0001) with N-terminal pro-B-type natriuretic peptide (&rgr;: −0.35), high-sensitive troponin T (&rgr;: −0.28), hematocrit (&rgr;: 0.34), glomerular filtration rate (&rgr;: 0.19), EuroSCORE (&tgr;: 0.20), and left ventricular ejection fraction class (&tgr;: 0.12). Thirty-day nonsurvivors had a lower Sco2min-ox than survivors (median 58% [95% CI, 50.7–62%] vs. 64% [95% CI, 64–65%]; P < 0.0001). Receiver-operating curve analysis of Sco2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68–0.73%; P < 0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69–0.86%; P < 0.0001) in patients with a EuroSCORE more than 10. Logistic regression based on different EuroSCORE categories (0–2; 3–5, 6–10, >10), Sco2min-ox, and duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than 50% is an independent risk factor for 30-day and 1-yr mortality. Conclusions: Preoperative Sco2 levels are reflective of the severity of cardiopulmonary dysfunction, associated with short- and long-term mortality and morbidity, and may add to preoperative risk stratification in patients undergoing cardiac surgery.

Twenty-Four–Hour Holter Monitor Follow-Up Does Not Provide Accurate Heart Rhythm Status After Surgical Atrial Fibrillation Ablation Therapy: Up to 12 Months Experience With a Novel Permanently Implantable Heart Rhythm Monitor Device

Background— Twenty-four–hour Holter monitoring (24HM) is commonly used to assess cardiac rhythm after surgical therapy of atrial fibrillation (AF). However, this “snapshot” documentation leaves a considerable diagnostic window and only stores short-time cardiac rhythm episodes. To improve accuracy of rhythm surveillance after surgical ablation therapy and to compare continuous heart rhythm surveillance versus 24HM follow-up intraindividually, we evaluated a novel implantable continuous cardiac rhythm monitoring (IMD) device (Reveal XT 9525). Methods and Results— Forty-five cardiac surgical patients (male 37, mean age 69.7±9.2 years) with a mean preoperative AF duration of 38±45 m were treated with either left atrial epicardial high-intensity focus ultrasound ablation (n=33) or endocardial cryothermy (n=12) in case of concomitant mitral valve surgery. Rhythm control readings were derived simultaneously from 24HM and IMD at 3-month intervals with a total recording of 2021 hours for 24HM and 220 766 hours for IMD. Mean follow-up was 8.30±3.97 m (range 0 to 12 m). Mean postoperative AF burden (time period spent in AF) as indicated by IMD was 37±43%. Sinus rhythm was documented in 53 readings of 24HM, but in only 34 of these instances by the IMD in the time period before 24HM readings (64%, P<0.0001), reflecting a 24HM sensitivity of 0.60 and a negative predictive value of 0.64 for detecting AF recurrence. Conclusion— For “real-life” cardiac rhythm documentation, continuous heart rhythm surveillance instead of any conventional 24HM follow-up strategy is necessary. This is particularly important for further judgment of ablation techniques, devices as well as anticoagulation and antiarrhythmic therapy.

A Comprehensive Evaluation of Rhythm Monitoring Strategies for the Detection of Atrial Fibrillation Recurrence: Insights from 647 Continuously Monitored Patients and Implications for Monitoring After Therapeutic Interventions

Background— Intermittent rhythm monitoring (IRM) to detect atrial fibrillation (AF) recurrence is employed to evaluate the success of therapeutic interventions. In a large population of patients with continuous monitoring (CM), we investigated the sensitivity of various frequencies and durations of IRM strategies on the detection of AF recurrence, the dynamics behind AF recurrence detection, and we describe measures to evaluate temporal AF recurrence. Methods and Results— Rhythm histories of 647 patients (mean AF burden, 0.12±0.22; median, 0.014; 687 patient-years) with implantable CM devices were reconstructed and analyzed. With the use of computationally intensive simulation, the sensitivity of IRM of various frequencies and durations on the identification of AF recurrence was evaluated. Prolonged-duration IRM was superior to shorter IRM (P<0.0001). However, even with aggressive IRM strategies, AF recurrence was not detected in a great proportion of patients. The temporal AF burden aggregation (AF density) was directly related to IRM sensitivity (P<0.0001). Even at similar AF burdens, patients with high-density AF required higher-frequency or prolonged-duration IRM to achieve the same sensitivity as in low-density AF (P<0.0001). Patients with high-density, low-burden AF benefit the most from CM for detection of AF recurrence. Conclusions— IRM follow-up is significantly inferior to CM. IRM strategies will not identify AF recurrence in a great proportion of patients at risk. Temporal AF characteristics play a significant role in AF recurrence detection with the use of IRM. For the scientific, evidence-based evaluation of AF treatments, CM should be strongly recommended. Prospective studies are required to evaluate whether CM to guide clinical management can also improve patient outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00806689.

Factors associated with the development of aortic valve regurgitation over time after two different techniques of valve-sparing aortic root surgery

OBJECTIVE Early results after aortic valve-sparing root reconstruction are excellent. Longer-term follow-up, especially with regard to aortic valve function, is required for further judgment of these techniques. METHODS Between July of 1993 and September of 2006, 108 consecutive patients (mean age 53.0 +/- 15.8 years) underwent the Yacoub operation (group Y) and 83 patients underwent the David operation (group D). Innovative multilevel hierarchic modeling methods were used to analyze aortic regurgitation over time. RESULTS In general, aortic regurgitation increased with time in both groups. Factors associated with the development of a significant increase in aortic regurgitation were Marfan syndrome, concomitant cusp intervention, and preoperative aortic anulus dimension. In Marfan syndrome, the initial aortic regurgitation was higher in group Y versus group D (0.56 aortic regurgitation vs 0.29 aortic regurgitation, P = .049), whereas the mean annual progression rate of aortic regurgitation was marginally higher in group Y (0.132 aortic regurgitation vs 0.075 aortic regurgitation, P = .1). Concomitant cusp intervention was associated with a significant aortic regurgitation increase in both groups (P < .0001). There was a trend that smaller preoperative aortic annulus diameters in group D and larger diameters in group Y were associated with increased aortic regurgitation over time. CONCLUSION In regard to aortic regurgitation grade over time, patients with Marfan syndrome and a large preoperative aortic annulus diameter were better treated with the reimplantation technique, whereas those with a smaller diameter were better treated with the remodeling technique. Concomitant free-edge plication of prolapsing cusps was disadvantageous in both groups. Considering these factors may serve to improve the aortic valve longevity after valve-sparing aortic root surgery.

A Critical Reappraisal of the Ross Operation Renaissance of the Subcoronary Implantation Technique

Background— The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle. Methods and Results— Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44±13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9±2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure–related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4±6.2/3.7±2.1 mm Hg across the autograft and 15.3±9.4/7.6±5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%). Conclusion— Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.

Fourteen years' experience with 501 subcoronary Ross procedures: surgical details and results.

OBJECTIVE During the past decade the Ross procedure using the full root has become the predominant surgical technique. However, progressive autograft dilatation and eventual failure remain a concern. Here we report on the surgical techniques and results of the subcoronary technique over a 14-year period. METHODS A total of 501 patients (mean age, 44.9 ± 12.9 years; 117 female; 384 male) were operated on from June 1994 to December 2007. The follow-up database, with a completeness of 98.2%, was closed on December 2008, comprising of 2931 patient-years with a mean follow-up of 5.9 ± 3.6 years (range, 0.1-14.1 years). RESULTS Surgical details are presented. Early and late mortality were 0.4% (n = 2) and 4% (n = 20), respectively, valve-related mortality was 1.2% (n = 6), whereas the overall survival did not differ from that of the normal population. Neurologic events occurred in 22 patients, major bleeding in 9, autograft endocarditis in 8, and homograft endocarditis in 10. Freedom from autograft and homograft reoperation was 91.9% at 10 years. For the majority of patients, hemodynamics was excellent and no root dilatation was observed. CONCLUSIONS Midterm results after the original subcoronary Ross procedure are excellent, including normal survival and low risk of valve-related morbidity. Longer-term results are necessary for continuous judgment of the subcoronary technique.

Mitochondrial DNA deletions and the aging heart.

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977 bp deletion of human mtDNA still many unanswered questions remain. Comparing mtDNA copy levels in different tissues revealed that cardiac muscle had the highest, while the cortex cerebelli showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy number showed no changes during aging. In heart tissue, the amount of 4977 bp mtDNA deletion increased in an age-dependent manner showing significant differences at the age of 40 years and older (p<0.005). In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis. Interestingly, OS induced apoptosis only in transformed human fibroblasts by activation of the intrinsic (mitochondrial-mediated) signalling pathway as indicated by morphological damage of mitochondria, DNA laddering and increase of the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

Autograft Regurgitation and Aortic Root Dimensions After the Ross Procedure The German Ross Registry Experience

Background— Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation. Methods and Results— Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2±15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n =521; root replacement, n =493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41±3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique. Conclusions— The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied.

Autograft Reinforcement to Preserve Autograft Function After the Ross Procedure A Report From the German-Dutch Ross Registry

Background— Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. Methods and Results— 1335 adult patients (mean age:43.5±12.0 years) underwent a Ross procedure (subcoronary, SC, n=637; root replacement, Root, n=698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean:6.09±3.97, range:0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (Root−R) group was associated with a 6× increased reoperation rate compared to Root with R (Root+R), SC with R (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%, respectively; P<0.001). SC and Root groups had similar rate of aortic regurgitation (AR) development over time. Root+R patients had no progression of AR, whereas Root−R had 6 times higher AR development compared to Root+R. In SC, R had no remarkable effect on the annual AR progression. The SC technique was associated with lower rates of autograft dilatation at all levels of the aortic root compared to the Root techniques. R did not influence autograft dilatation rates in the Root group. Conclusions— For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure.

Long-Term Results of 203 Young and Middle-Aged Patients With More Than 10 Years of Follow-Up After the Original Subcoronary Ross Operation

BACKGROUND The choice of prosthesis for aortic valve replacement in young and middle-aged patients remains challenging owing to the accelerated degeneration of bioprostheses in these age groups and the risks of thromboembolism and bleeding with mechanical valves. Theoretically, the living pulmonary autograft (Ross operation) would be advantageous. Long-term results of the various Ross techniques are needed for defining the value of this surgical concept. METHODS Of a total of 576 subcoronary Ross patients operated on between June 1994 and June 2011, we report on 203 consecutive subcoronary patients (mean age, 47.2±13.6 years, 155 male, 2,491 patient-years) with a follow-up of at least 10 years (mean, 12.3±2.9 years). RESULTS Early and late mortality were 0.98% (n=2) and 11.4% (n=23). Valve-related mortality was 2.5% (n=5). Survival did not differ from that of the general German population. Freedom from autograft or allograft reoperation was 92.2% at 10 years and 87.1% at 15 years. Five major bleeding (0.20%/patient-year) and 11 thromboembolic events (0.44%/patient-year) occurred in 5 and 10 patients, respectively. Neither a systematic increase in aortic regurgitation nor an increase in root dimensions with time could be observed. In the vast majority of patients, valvular hemodynamics at latest echocardiographic follow-up were excellent. CONCLUSIONS Long-term results of the original subcoronary Ross operation reveal normal survival, excellent hemodynamics, low risk of thromboembolism or bleeding, and small risk for reoperation. These results favor the pulmonary autograft concept in young and middle-aged patients in experienced centers and may serve to better define its role in surgical treatment of aortic valve disease in these patients.