Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat.

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes. To identify ventricle-specific mitochondrial molecular and functional signatures, we established rat models with two slowly developing disease stages (compensated and decompensated) in response to pulmonary artery banding (PAB) or ascending aortic banding (AOB). Genome-wide transcriptomic and proteomic analyses were used to identify differentially expressed mitochondrial genes and proteins and were accompanied by a detailed characterization of mitochondrial function and morphology. Two clearly distinguishable disease stages, which culminated in a comparable systolic impairment of the respective ventricle, were observed. Mitochondrial respiration was similarly impaired at the decompensated stage, while respiratory chain activity or mitochondrial biogenesis were more severely deteriorated in the failing LV. Bioinformatics analyses of the RNA-seq. and proteomic data sets identified specifically deregulated mitochondrial components and pathways. Although the top regulated mitochondrial genes and proteins differed between the RV and LV, the overall changes in tissue and cardiomyocyte gene expression were highly similar. In conclusion, mitochondrial dysfuntion contributes to disease progression in right and left heart failure. Ventricle-specific differences in mitochondrial gene and protein expression are mostly related to the extent of observed changes, suggesting that despite developmental, anatomical and functional differences mitochondrial adaptations to chronic pressure overload are comparable in both ventricles.

Surgical Ablation of Atrial Fibrillation in High-Risk Patients: Success versus Risk.

BACKGROUND: Surgical atrial ablation is evaluated by surgeons in relation to the estimated surgical risk. We analyze whether high-risk patients (HRPs) experience risk escalation by ablation procedures. METHODS: The CASE-Atrial Fibrillation (AF) registry is a prospective, multicenter, all-comers registry of atrial ablation in cardiac surgery. We analyzed the 1-year outcome regarding survival and rhythm endpoints of 1,000 consecutive patients according to the operative risk classification (EuroSCORE II ≤ 2 vs. >2). RESULTS: Higher NYHA (New York Heart Association) score, ischemic heart failure, status poststroke, renal insufficiency, chronic obstructive pulmonary disease, and diabetes mellitus were strongly represented in HRPs. HRPs exhibit more left ventricular ejection fraction < 40% (19.2 vs. 8.8%; p < 0.001) but identical left atrial diameter and left ventricular end-diastolic diameter compared with low-risk patients (LRPs). CHA2DS-Vasc-score (2.4 ± 1 vs. 3.6 ± 1.5; p < 0.001), sternotomies, combination surgeries, coronary artery bypass graft, and mitral valve procedures were increased in HRPs. LRPs underwent stand-alone ablations as well. Ablation energy did not differ. Left atrial appendage closure was performed in up to 86.1% (mainly cut-and-sew procedures). Mortality corresponded to the original risk class without an escalation that may be related to ablation, stroke rate, or myocardial infarction. A total of 60.6% of HRPs versus 75.1% of LRPs were discharged in sinus rhythm. Long-term EHRA (European Heart Rhythm Association) score symptoms were lower in HRPs. Repeated rhythm therapies were rare. Additional antiarrhythmics received a minority without group dependency. A total of 1.6 versus 4.1% of HRPs (p = 0.042) underwent long-term stroke; excess mortality was not observed. Anticoagulation remained common in HRPs. CONCLUSION: Surgical risk and long-term mortality are determined by the underlying disease. In HRPs, freedom from AF and symptom relief can be achieved. Preoperative risk scores should not lead to withholding an ablation procedure.

Surgical Ablation of Permanent Atrial Fibrillation: Age, LV Dilatation, Obesity.

OBJECTIVES: Although concomitant surgical ablation can help to reach freedom from atrial fibrillation (FREEAF) even in patients with permanent atrial fibrillation (AF), some cardiac surgeons hesitate to perform concomitant ablation to avoid perioperative risk escalation. Here, we investigated outcome and predicators of therapeutic success of concomitant surgical ablation in an all-comers study. METHODS: Ablation-naïve patients with formerly accepted permanent AF (FAP, n = 41) or paroxysmal AF (parAF, n = 24) underwent concomitant epicardial bipolar radio frequency ablation and implantable loop recorder (ILR) at two surgical departments. Follow-up examination for 24 months included electrocardiogram, ILR readout, 24h Holter monitoring, echocardiography, and blood sampling. RESULTS: Eighty-six percent of parAF and 70% of FAP patients reached FREEAF (month 24). Mortality was low (parAF/FAP: 5.3 ± 0.2%/4.1 ± 0.3%; p < 0.05; EuroScoreII; 6.1 ± 0.7%/6.4 ± 0.4%, p = ns) and no strokes occurred. FREEAF induced atrial reverse remodeling (left atrial [LA] diameter: -6.7 ± 2.2 mm) and improved cardiac function (left ventricular ejection fraction [LVEF]: +7.3 ± 2.8%), while AF resulted in further atrial dilation (+8.0 ± 1.0 mm, p < 0.05) and LVEF reduction (-7.0 ± 1.3%, p < 0.05). Higher LV (odds ratio [OR]: 1.164) and LA diameter (OR: 1.218), age (OR: 1.180) and body mass index (BMI) (OR: 1.503) increased the risk factors of AF recurrence. Patients remaining in sinus rhythm (SR) demonstrated a decrease in BMI, while AF recurrence was associated with stable overweight. Further aging did not reduce FREEAF. CONCLUSIONS: Long-term SR is achievable by concomitant surgical ablation even in FAP patients. Therefore, it should be offered routinely. Obesity influences therapeutic long-term success but may also offer addressable therapeutic targets to reach higher FREEAF rates.

Remote ischemic preconditioning in patients undergoing cardiac surgery with six ischemic cycles.

BACKGROUND: We have previously shown that remote ischemic preconditioning (RIP), which utilizes in part the extracellular RNA (eRNA)/RNase1 pathway, can induce ischemic tolerance in humans. Because RIP has thus far been tested only with four cycles of extremity ischemia/reperfusion, we investigated the influence of six cycles of ischemia on the eRNA/RNase1 pathway in cardiac patients. METHODS: Six cycles of RIP were carried out in 14 patients undergoing cardiac surgery. Blood samples were taken at 13 timepoints during surgery and at three timepoints after surgery for determining serum levels of RNase1, eRNA, and TNF-α. Trans-cardiac gradients between the myocardial blood inflow and outflow were calculated. RESULTS: Between the fourth and the sixth RIP cycles, a noticeable increase in the levels of eRNA (fourth: 151.6 (SD: 44.2) ng/ml vs sixth: 181.8 (SD: 87.5) ng/ml, p = .071), and a significant increase in RNase1 (fourth: 151.1 (SD: 42.6) U/ml vs sixth: 175.3 (SD: 41.2) U/ml, p = .001), were noted. The trans-cardiac gradients of RNase1 and eRNA before and after ischemia were not significantly different (p = .158 and p = .221; p = .397 and p = .683, respectively). Likewise, the trans-cardiac gradient of TNF-α was similar before and after ischemia. During the first 48 h after the surgery, RNase1 activity rose significantly and exceeded baseline values (135.7 (SD: 40.6) U/ml before and 279.2 (SD: 85.6) U/ml after surgery, p = .001) as did eRNA levels (148,6 (SD: 35.4) ng/ml before and 396.5 (SD: 154.5) ng/ml after surgery, p = .005), whereas TNF-α levels decreased significantly (91.7 (SD: 47.7) pg/ml before and 35.7 (SD: 36.9) pg/ml after surgery, p = .001). CONCLUSION: Six RIP cycles increased the RNase1 levels significantly above those observed with four cycles. More clinical data are required to show whether this translates into a benefit for patients.

Rationale and Initiative of the Impella in Cardiac Surgery (ImCarS) Register Platform.

OBJECTIVES: Cardiac support systems are being used increasingly more due to the growing prevalence of heart failure and cardiogenic shock. Reducing cardiac afterload, intracardiac pressure, and flow support are important factors. Extracorporeal membrane oxygenation (ECMO) and intracardiac microaxial pump systems (Impella) as non-permanent MCS (mechanical circulatory support) are being used increasingly. METHODS: We reviewed the recent literature and developed an international European registry for non-permanent MCS. RESULTS: Life-threatening conditions that are observed preoperatively often include reduced left ventricular function, systemic hypoperfusion, myocardial infarction, acute and chronic heart failure, myocarditis, and valve vitia. Postoperative complications that are commonly observed include severe systemic inflammatory response, ischemia-reperfusion injury, trauma-related disorders, which ultimately may lead to low cardiac output (CO) syndrome and organ dysfunctions, which necessitates a prolonged ICU stay. Choosing the appropriate device for support is critical. The management strategies and complications differ by system. The "heart-team" approach is inevitably needed.However despite previous efforts to elucidate these topics, it remains largely unclear which patients benefit from certain systems, when is the right time to initiate (MCS), which support system is appropriate, what is the optimal level and type of support, which therapeutic additive and supportive strategies should be considered and ultimately, what are the future prospects and therapeutic developments. CONCLUSION: The European cardiac surgical register ImCarS has been established as an IIT with the overall aim to evaluate data received from the daily clinical practice in cardiac surgery. Interested colleagues are cordially invited to join the register. CLINICAL REGISTRATION NUMBER: DRKS00024560. POSITIVE ETHICS VOTE: AZ 246/20 Faculty of Medicine, Justus-Liebig-University-Gießen.

The Same is Not the Same: Device Effect during Bipolar Radiofrequency Ablation of Atrial Fibrillation.

BACKGROUND: Different ablation devices deliver the same type of energy but use individual control mechanisms to estimate efficacy. We compared patient outcome after the application of radiofrequency ablation systems, using temperature- or resistance-control in paroxysmal and persistent atrial fibrillation (AF). METHODS: This is an unselected all-comers study. Patients underwent standardized left atrial (paroxysmal atrial fibrillation, [PAF] n = 31) or biatrial ablation (persistent atrial fibrillation [persAF] n = 61) with bipolar RF from October 2010 to June 2013. Patients with left atrial dilatation (up to 57 mm), reduced left ventricular (LV) function, and elderly were included. We used resistance-controlled (RC) or temperature-controlled (TC) devices. We amputated atrial appendices and checked intraoperatively for completeness of pulmonary vein exit block. All patients received implantable loop recorders. Follow-up interval was every 6 months. Antiarrhythmic medical treatment endured up to month 6. RESULTS: We reached 100% freedom from atrial fibrillation (FAF) in PAF. In perAF 19% of the RC but 82% of the TC patients reached FAF (12 months; p < 0.05). TC patients exhibited higher creatine kinase-muscle/brain (CK-MB) peak values. In persAF, CK-MB-levels correlated to FAF. No and no mortality (30 days) was evident. Twelve-month mortality did not correlate to AF type, AF duration, LV dimension, or function and age. Prolonged need of oral anticoagulants was 90.1% (RC) and 4.5% (TC). CONCLUSION: In patients with persAF undergoing RF ablation, TC reached higher FAF than RC. Medical devices are not "the same" regarding effectiveness even if used according to manufacturer's instructions. Thus, putative application of "the same" energy is not always "the same" efficacy.

Influence of Left Atrial Appendage Amputation on Natriuretic Peptides-A Randomized Controlled Trial.

BACKGROUND: Closure or amputation of the left atrial appendage (LAA) is a common therapy for atrial fibrillation (AF). As the LAA is a hormone-producing organ, however, amputation is still somewhat controversial. We examined patients after surgical AF therapy with or without LAA amputation to determine the influence of LAA amputation on pro-atrial natriuretic peptide (proANP) and B-type natriuretic peptide (BNP) plasma levels and on clinical severity of heart failure. METHODS: Twenty-one consecutive patients were prospectively randomized to either undergo LAA amputation (n = 10) or no LAA amputation (n = 11) between 05/2015 and 10/2015. All patients underwent coronary and/or valve surgery and concomitant AF surgery with either cryoablation (n = 3) or radio frequency ablation (n = 17). ProANP and BNP levels were measured preoperatively and until 800 days postoperatively. RESULTS: Baseline proANP values were comparable between the groups (without LAA amputation: 4.2 ± 2.1 nmol/L, with LAA amputation: 5.6 ± 3.6 nmol/L). Postoperatively, proANP levels rose markedly in both groups. Even after LAA amputation, proANP levels remained elevated for 7 days postoperatively but fell to baseline levels at day 31 and remained on baseline level at 800 days postoperatively. ProANP levels in the LAA amputation group (5.8-9.7 nmol/L) were not significantly lower than in the group without LAA amputation (9.2-14.1 nmol/L; p = 0.357). BNP levels also rose after surgery in both groups until day 7. At 800 days after surgery, BNP levels were back at baseline levels in both groups. Clinical follow-up at 2 years postoperatively showed no difference in heart failure symptoms or need for heart failure medication between the groups. CONCLUSION: In contrast to commonly held beliefs about the endocrine and reservoir functions of the LAA, there seems to be no clinically relevant detrimental effect of LAA amputation on natriuretic peptide levels and severity of heart failure until up to 2 years postoperatively.

Fibrin-Coated Collagen Fleece Seems to Prevent Sternal Instability after Cardiac Surgery: A Matched Pair Data Analysis.

BACKGROUND: To examine if fibrin-coated collagen fleece (Tachosil) interferes with bone and wound healing when it is used on the cut surface of the sternum after median sternotomy. METHODS: A total of 25 patients with osteoporotic sternal disorders were treated with fibrin-coated collagen fleece at the cut surface of the sternum after median sternotomy (therapy group). We compared the occurrence of impaired wound healing and sternal instability, reoperation rate, and 30-day mortality with a control group of 25 case-matched patients. After matching for age, gender, and risk factors for sternal instability (diabetes mellitus, osteoporosis, body mass index, nicotine consumption), both groups were comparable. RESULTS: Sternal instability occurred in one (4%) patient in the study group and in five (20%) patients in the control group. Impaired wound healing occurred in one (4%) patient in the therapy group and two (8%) patients in the control group. Reoperation was necessary in four (16%) patients in the therapy group and 6 (24%) patients in the control group. The 30-day mortality occurred in six (24%) patients in the therapy group and four (16%) patients in the control group. CONCLUSIONS: The use of fibrin-coated collagen fleece on the cut surface of the sternum in patients with osteoporosis does not impair bone and wound healing. Furthermore, it seems to result in less sternal instability. A larger prospective study is necessary to verify the results of this explorative study.

Predicting Cardiac Surgery-Associated Acute Kidney Injury Using a Combination of Clinical Risk Scores and Urinary Biomarkers.

BACKGROUND: Prediction, early diagnosis, and therapy of cardiac surgery-associated acute kidney injury (CSA-AKI) are challenging. We prospectively tested a staged approach to identify patients at high risk for CSA-AKI combining clinical risk stratification and early postoperative quantification of urinary biomarkers for AKI. METHODS: All patients, excluding those on chronic hemodialysis, undergoing scheduled surgery with cardiopulmonary bypass between August 2015 and July 2016 were included. First, patients were stratified by calculating the Cleveland clinic score (CCS) and the Leicester score (LS). In high-risk patients (defined as LS > 25 or CCS > 6), urinary concentrations of biomarkers for AKI ([TIMP-2]*[IGFBP-7]) were evaluated 4 hours postoperatively. CSA-AKI was observed until postoperative day 6 and classified using the Kidney Disease: Improving Global Outcomes criteria. RESULTS: AKI occurred in 352 of613 patients (54%). In high-risk patients, AKI occurred more frequently than in low-risk patients (66 vs. 49%; p = 0.001). In-hospital mortality after AKI stage 2 (15%) or AKI stage 3 (49%) compared with patients without AKI (1.8%; p = 0.001) was increased. LS was predictive for all stages of AKI (area under the curve [AUC] 0.601; p < 0.001) with a poor or fair accuracy, while CCS was only predictive for stage 2 or 3 AKI (AUC 0.669; p < 0.001) with fair accuracy. In 133 high-risk patients, urinary [TIMP-2]*[IGFBP-7] was significantly predictive for all-stage AKI within 24 hours postoperatively (AUC 0.63; p = 0.017). However, for the majority of AKI (55%), which occurred beyond 24 hours postoperatively, urinary [TIMP-2]*[IGFBP-7] was not significantly predictive. Sensitivity for all-stage AKI within 24 hours was 0.38 and specificity was 0.81 using a cutoff value of 0.3. CONCLUSION: CSA-AKI is a relevant and frequent complication after cardiac surgery. Patients at high risk for CSA-AKI can be identified using clinical prediction scores, however, with only poor to fair accuracy. Due to its weak test performance, urinary [TIMP-2]*[IGFBP-7] quantification 4 hours postoperatively does not add to the predictive value of clinical scores.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

[DGEM Guideline "Clinical Nutrition in Critical Care Medicine" - short version]. / DGEM-Leitlinie: Klinische Ernährung in der Intensivmedizin ­ Kurzversion.

PURPOSE: Variations of clinical nutrition may affect outcome of critically ill patients. Here we present the short version of the updated consenus-based guideline (S2k classification) "Clinical nutrition in critical care medicine" of the German Society for Nutritional Medicine (DGEM) in cooperation with 7 other national societies. The target population of the guideline was defined as critically ill adult patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g. mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. We considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of international societies. The liability of each recommendation was indicated using linguistic terms. Each recommendation was finally validated and consented by a Delphi process. RESULTS: The short version presents a summary of all 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in the target population. A specific focus is the adjustment of nutrition according to the phases of critical illness, and to the individual tolerance to exogenous substrates. Among others, recommendations include the assessment of nutritional status, the indication for clinical nutrition, the timing, route, magnitude and composition of nutrition (macro- and micronutrients) as well as distinctive aspects of nutrition therapy in obese critically ill patients and those with extracorporeal support devices. CONCLUSION: The current short version of the guideline provides a concise summary of the updated recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring pharmacological and/or mechanical support. The validity of the guideline is approximately fixed at five years (2018 - 2023).

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Heart and Mitochondria: Pathophysiology and Implications for Cardiac Surgeons.

Excluding the heart from systemic circulation during cardiac surgery renders the myocardium ischemic, resulting in cardiac damage. In addition, another hit to the myocardium will occur upon restoration of blood flow, in the reperfusion phase. Experimental data from animal models have revealed that loss of cardiac metabolic flexibility and mitochondrial dysfunctions contributes to contractile impairment in hypertrophied, failing, obese, and diabetic hearts. Such diseased hearts are prone to myocardial ischemia-reperfusion (I/R) injury. Although analyses in human cardiac samples are not as comprehensive as animal data, similar disease-associated metabolic and mitochondrial changes exist. Considering increasing age and comorbidities in patients nowadays, it is not surprising that I/R injuries remain a major cause of morbidity and mortality after cardiac surgery. Mitochondria have emerged as critical targets but also key regulators of myocardial I/R injury, and the extent of mitochondrial damage is a major determinant of myocardial I/R injury. Although cardioprotective mechanisms are diverse, many come together and involve steps at the point of mitochondria. We will, therefore, provide a description of mitochondrial alterations observed in various cardiac disease states and discuss the current experimental knowledge of the role of mitochondria in I/R and of potential protective mechanisms against myocardial I/R injury involving mitochondria. Within this review, we will focus on the protection against I/R injury conferred by caloric restriction (CR) and by ischemic conditioning. Further research is needed to establish whether strategies targeting mitochondria, which have been proposed from preclinical studies, could be translated into cardioprotective therapies against I/R injury in patients.

Mechanisms Involved in Premature Aging in the Heart-Is There an Implication for Cardiac Surgery?

During the past century, life expectancy has risen in Germany from 35.6 and 38.5 years in men and women (1871/1881) to 78.2 and 83.1 years (2013/2015). In recent years, the dominance of chronic diseases as major contributors to total global mortality has emerged. The incidence of cardiovascular diseases (CVD) increases in westernized societies and projected trends suggest that by 2030, CVD alone will also be responsible for more deaths in low-income countries than infectious diseases. The occurrence of CVD also seems to correlate to a further increase of biological age within westernized societies. Therefore, age-associated changes in the heart are an issue of high interest in cardiac surgery. The chronological age is a prognostic marker in some clinical scoring systems. However, it does not represent an adequate estimation of the biological age of patients or their perioperative risk. In fact, frailty might be a more powerful predictor for normal perioperative course or risk escalation. An unhealthy, sedentary lifestyle can induce premature aging of vessels and myocardium. Understanding the age-associated genetic, biochemical, and pathophysiological changes can help identify the therapeutic capability of aged myocardium. Future "therapeutic myocardial rejuvenation" may represent a powerful tool for the stabilization of the perioperative course in aged patients. In this review, we will focus on selected mediators or conditions with impact on age-associated myocardial changes with a major focus on obesity and discuss potential therapeutic strategies to utilize or modify these mediators.

Stentless Bioprostheses for Aortic Valve Replacement in Octogenarians: The Influence of Coronary Artery Disease.

BACKGROUND: We sought to determine the long-term results of stentless biological heart valve replacement in octogenarians to find out whether coronary artery disease or the coronary artery bypass grafting (CABG) procedure itself influences survival in these aged patients. METHODS: From 4,012 patients undergoing aortic valve replacement (AVR) with a stentless prosthesis (Freestyle, Medtronic) at a single center, 721 patients were older than 80 years. They had a mean age of 83 ± 2 (2,320 patient years), the male/female ratio was 42:58, NYHA (New York Heart Association) class I and II was prevalent in 22.8%, preoperative atrial fibrillation (AF) in 20.6%, coronary artery disease in 56.1%, mitral valve disease in 12.5%, and aortic disease in 3.5%. Follow-up included a total of 11,546 patient years (mean follow-up time: 74 ± 53 months); follow-up mortality data were 96.3% complete. RESULTS: In these aged patients, 30-day mortality in the isolated AVR group (10.3%) was similar to that in the AVR + CABG group (13.4%). Although long-term survival (15 years) in the octogenarian population is low (9% in the AVR group and 6% in the AVR + CABG group), it was not different (p = 0.191) between patients with and without coronary artery disease. The stroke rate and the myocardial infarction rate, respectively, in the AVR + CABG group (0.43%/100 patient years and 0.17%/100 patient years) were only insignificantly higher than that in the isolated AVR group (each 0.01%/100 patient years). The actuarial freedom from reoperation was 99% in both the groups. CONCLUSION: Use of the Freestyle stentless valve prosthesis for AVR is feasible also in octogenarians. The existence of coronary artery disease leads to concomitant bypass surgery, but not a higher level of perioperative or long-term mortality.

Prophylactic intra-aortic balloon counterpulsation before surgical myocardial revascularization in patients with acute myocardial infarction.

INTRODUCTION: Prophylactic intra-aortic balloon counterpulsation (pIABC) is recommended for high-risk patients undergoing coronary artery bypass grafting (CABG) surgery. Criteria for high-risk patients benefiting from pIABC are unclear. This study aimed to specifically describe the effect of pIABC on outcomes of patients with acute myocardial infarction (AMI) undergoing CABG. METHODS: In 178 of 484 AMI patients (non-ST-segment elevation myocardial infarction [NSTEMI] or ST-segment elevation myocardial infarction [STEMI] ≤5 days before surgery) without cardiogenic shock who underwent CABG between 2008 and 2013, pIABC was initiated preoperatively. After propensity score matching, the outcomes of 400 patients were analyzed (pIABC: 150; Control: 250). RESULTS: After propensity score matching, baseline and operative characteristics were balanced between the groups except for a higher rate of patients with a left ventricular ejection fraction (LVEF)≤30% in the pIABC group (26% vs. Control: 13%; p=0.032). Seven point two percent (7.2%) of the control patients received an IABP intraoperatively or postoperatively. Postoperative extracorporeal life support (ECLS) was only needed in the control group (1.2% vs. 0%; p=0.01). Postoperative plasma curves of troponin I, creatine kinase (CK) and creatine kinase isoform MB (CK-MB) levels were reduced in the pIABC group compared with the control group. In-hospital mortality was reduced in the pIABC group (3.3% vs. control: 6.4%; p=0.18). After multivariate adjustment for other preoperative risk factors, pIABC was significantly protective concerning in-hospital mortality (HR 0.56; 95%-CI 0.023-0.74; p=0.021). Mortality (pIABC vs. control) was more affected in patients with preoperative LVEF≤30% (2/36 (5.6%) vs. 6/31 (19%); heart rate (HR) 0.25; 95%-CI 0.046-1.3; p=0.13) compared with LVEF>30% (3/114 (2.6%) vs. 10/219 (4.6%); HR 0.56; 95%-CI 0.15-2.1; p=0.55). Long-term survival did not differ between the groups. CONCLUSIONS: pIABC in CABG for AMI is associated with reduced perioperative cardiac injury and in-hospital mortality. Long-term survival is not affected.

Cardiac effects of echinocandins after central venous administration in adult rats.

Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. In vitro studies and clinical case reports revealed a possible impact of echinocandin treatment on cardiac function. The aim of our study was to evaluate echinocandin-induced cardiac failure. Using an in vivo rat model, we assessed hemodynamic parameters and time to hemodynamic failure after central venous application (vena jugularis interna) of anidulafungin (low-dose group, 2.5 mg/kg body weight [BW]; high-dose group, 25 mg/kg BW), caspofungin (low-dose group, 0.875 mg/kg BW; high-dose group, 8.75 mg/kg BW), micafungin (low-dose group, 3 mg/kg BW; high-dose group, 30 mg/kg BW), and placebo (0.9% sodium chloride). Left ventricular heart tissue was collected to determine mitochondrial enzyme activity via spectrophotometric measurements. mRNA expression of transcriptional regulators and primary mitochondrial transcripts, mitochondrial DNA (mtDNA) content, and citrate synthase activity were also explored. Animals receiving high-dose anidulafungin or caspofungin showed an immediate decrease in hemodynamic function. All of the subjects in these groups died during the observation period. Every animal in the untreated control group survived (P < 0.001). Hemodynamic failure was not noticed in the anidulafungin and caspofungin low-dose groups. Micafungin had no impact on cardiac function. In analyzing mitochondrial enzyme activity and mitochondrial transcripts, we found no association between echinocandin administration and the risk for hemodynamic failure. Further experimental studies are needed to elucidate the underlying mechanisms involved in cardiotoxic echinocandin effects. In addition, randomized controlled clinical trials are needed to explore the clinical impact of echinocandin treatment in critically ill patients.

Prophylactic intra-aortic balloon counterpulsation in cardiac surgery: it is time for clear evidence.

In the previous issue of Critical Care, Yu and colleagues report increased morbidity and mortality in patients after myocardial infarction undergoing prophylactic intra-aortic balloon pump support before coronary artery bypass graft surgery. The impact of prophylactic intra-aortic balloon pump implantation before coronary artery bypass graft therapy still is controversially debated. However, Yu and colleagues emphasize further discussion and substantiate the need for a prospective randomized controlled trial on this subject.

Is warm or cold Calafiore blood cardioplegia better? Hemodynamic, metabolic, and electron microscopic differences.

BACKGROUND: Controversy exists as to whether warm or cold Calafiore blood cardioplegia (BCP) is better for cardiac preservation. Therefore, we compared hemodynamic performance, myocardial metabolism, and ultrastructural preservation in rat hearts after application of cold or warm BCP. MATERIALS AND METHODS: The hearts of 24 male Wistar rats were excised and inserted into a blood perfused isolated heart apparatus, and after a stabilization period of 30 minutes, either cold (4°C) or warm (36°C) Calafiore BCP was administered during an aortic clamping time of 90 minutes (12 rats each). Hearts clamped without BCP and hearts immediately excised in anesthesia served as worst case and no damage controls, respectively (n=3 each). During reperfusion, functional hemodynamic parameters were recorded in BCP groups, and myocardial oxygen consumption and lactate production were calculated. After perfusion fixation, the hearts of three rats in each group were investigated for cellular edema and mitochondrial damage by morphometry using transmission electron microscopy. RESULTS: Cardiac function after BCP application during aortic clamping showed a slightly better recovery with warm than with cold Calafiore BCP as indicated by higher left ventricular developed pressure (warm 97% of baseline, cold 68% of baseline) after warm BCP. Other hemodynamic parameters and coronary flow were not different between warm and cold BCP. Myocardial oxygen consumption and lactate production were similar under warm and cold conditions. Electron microscopy showed typical signs of ischemia in the ischemia group without BCP. Mitochondrial ultrastructure was well preserved in both BCP groups, but cellular edema was more pronounced with cold than with warm BCP. The qualitative analysis was confirmed by the morphometric cellular edema index and the volume-to-surface ratio of the mitochondria. CONCLUSION: Only mild differences were observed between warm and cold BCP in rats with respect to cardiac function, metabolism, and tissue preservation after aortic clamping. However, a small tendency toward better postischemic recovery was observed with warm BCP.