Lund Concept for De-airing of the Left Heart. Clinical Evaluation.

Background: Residual air accumulated air in the pulmonary veins constitutes a challenge to achievment of complete de-airing in open left heart surgery. To adress this problem, a conceptual method for de-airing was developed in Lund comprising bilateral opening of the pleurae to induce pulmonary collapse and a strategy with gradual pulmonary reperfusion and ventilation at weaning from cardiopulmonary bypass (CPB). Aim: To evaluate effectiveness and safety aspects of the Lund concept for de-airing. Methods and results: In the first paper a randomized controlled study was conducted comparing the Lund method to a standardized carbon dioxide (CO2) insufflation technique in twenty patients undergoing open left heart surgery. The number of cerebral microembolic signals (MES) was monitored by transcranial Doppler sonography (TCD) during de-airing and in the first ten minutes after CPB. Residual intracardiac air during the first ten minutes after CPB was graded by transesophageal echocardiography (TEE). The frequency of reopenings of the left ventricular (LV) vent during the first ten minutes after CPB was registered as well as the duration of the de-airing procedure. Compared to the CO2 insufflation technique, the Lund method resulted in fewer MES during de-airing (p6 kPa) despite compensational higher gas flows in the oxygenator at 30 minutes of CPB (p<0.001) and acidosis (pH<7.35) already at 15 min of CPB, (p<0.01). CO2 production (VCO2 mL/min) increased during CPB as did the respiratory quotient (RQ; p<0.001) secondary to the extraneously supplied CO2. The mean blood flow velocities in both MCAs increased secondary to increasing PaCO2 (p<0.001 at 45 and 60 minutes of CPB). rSo2 measured by near-infrared spectroscopy (NIRS) were also found higher at 30, 45 and 60 minutes of CPB (p<0.05, p<0.01 and p<0.01, respectively). Scanning electron microscope imaging the cardiotomy suction and LV vent line tubing showed a higher fraction of morphologically changed red blood cells in the CO2 insufflation group. In the third paper we aimed to study the contribution of each component constituting the Lund concept. In a randomized controlled study of twenty patients undergoing open left heart surgery, we compared a group with open pleurae and conventional pulmonary reperfusion and ventilation to a group with intact pleurae combined with staged pulmonary reperfusion and ventilation. During de-airing and in the first ten minutes after CPB, there was a lower number of MES in the group with open pleurae (p<0.05, p<0.01, respectively). A lower amount of residual intracardiac air was also registered in the group with open pleurae in up to six minutes after CPB (p<0.01). The LV vent was reopened fewer times in the group with open pleurae (p<0.001). De-airing time was also shorter in the group with open pleurae, 9 vs 14 minutes (p<0.05). In the fourth paper we studied the impact of single right pulmonary collapse on effectiveness of the Lund method and the effectiveness of a right superior pulmonary vein vent (RSPV). Twenty patients in two prospective cohorts with right pleura open and RSPV respectively, were compared to a historical control cohort from the first paper with bilateral open pleurae and left ventricular apical vent (LVAV). We found a higher number of MES after CPB in the group with single right pulmonary collapse and in the group with RSPV compared to bilateral pulmonary collapse and LVAV (p<0.001, p<0.01, respectively) but no differences in residual intracardiac air graded by TEE or in de-airing times. Conclusion: The Lund concept for de-airing was demonstrated to be an effective and safe alternative to the CO2 insufflation technique. The effectiveness of the Lund method depends primarily on bilateral pulmonary collapse and it may preferably be combined with a left ventricular apical vent

Risk Profiles for Aortic Dissection and Ruptured or Surgically Treated Aneurysms: A Prospective Cohort Study

Background: Community screening to guide preventive interventions for acute aortic disease has been recommended in high‐risk individuals. We sought to prospectively assess risk factors in the general population for aortic dissection (AD) and severe aneurysmal disease in the thoracic and abdominal aorta. Methods and Results: We studied the incidence of AD and ruptured or surgically treated aneurysms in the abdominal (AAA) or thoracic aorta (TAA) in 30 412 individuals without diagnosis of aortic disease at baseline from a contemporary, prospective cohort of middle‐aged individuals, the Malmö Diet and Cancer study. During up to 20 years of follow‐up (median 16 years), the incidence rate per 100 000 patient‐years at risk was 15 (95% CI 11.7 to 18.9) for AD, 27 (95% CI 22.5 to 32.1) for AAA, and 9 (95% CI 6.8 to 12.6) for TAA. The acute and in‐hospital mortality was 39% for AD, 34% for ruptured AAA, and 41% for ruptured TAA. Hypertension was present in 86% of individuals who subsequently developed AD, was strongly associated with incident AD (hazard ratio [HR] 2.64, 95% CI 1.33 to 5.25), and conferred a population‐attributable risk of 54%. Hypertension was also a risk factor for AAA with a smaller effect. Smoking (HR 5.07, 95% CI 3.52 to 7.29) and high apolipoprotein B/A1 ratio (HR 2.48, 95% CI 1.73 to 3.54) were strongly associated with AAA and conferred a population‐attributable risk of 47% and 25%, respectively. Smoking was also a risk factor for AD and TAA with smaller effects. Conclusions: This large prospective study identified distinct risk factor profiles for different aortic diseases in the general population. Hypertension accounted for more than half of the population risk for AD, and smoking for half of the population risk of AAA

Nygammal metod minskar neurologisk risk vid arcus aortae-kirurgi. Selektiv antegrad hjärnperfusion ger bra skydd, visar retrospektiv studie

nnominate artery and left carotid artery cannulation for antegrade brain perfusion allows accurate bilateral pressure-controlled brain perfusion. The aim of this study was to evaluate the incidence of adverse neurological events and 90-day mortality in 40 consecutive patients undergoing elective aortic arch repair using this technique. Forty consecutive patients underwent elective aortic arch repair using selective antegrade brain perfusion. The perfusion was instituted by cannulation of the innominate artery (using standard cannulae) and by direct cannulation of the left common carotid artery (using cannulae having a built-in-side arm for pressure monitoring). Bilateral radial artery and left common carotid artery pressure monitoring allowed precise, pressure-controlled bilateral brain perfusion. Bilateral selective antegrade brain perfusion was given with a perfusion rate of 4.6 ml to 15.9 ml/kg/min (mean 9.6 ml/kg/min). This was sufficient to obtain dual-controlled mean cerebral perfusion pressures of 50-70 mmHg as monitored simultaneously in the right radial artery and the left carotid artery. The incidence of stroke and transient neurological dysfunction was 2.5 % each. Ninety-day mortality was 2.5 %. Pressure-controlled, bilateral, selective antegrade brain perfusion by innominate artery cannulation seems to be a safe method for cerebral protection during elective aortic arch repair

Fondaparinux or enoxaparin: A comparative study of postoperative bleeding in coronary artery bypass grafting surgery.

Objectives. Preoperative treatment with anti-coagulants for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) exposes patients undergoing surgical revascularization to a higher risk of perioperative bleeding. The aim of this study was to compare the effect on bleeding and transfusion needs during cardiac surgery for patients treated with enoxaparin or fondaparinux. Design. Using a combined retrospective and prospective approach, we studied the outcome of 147 patients with NSTE-ACS referred to coronary artery bypass grafting in terms of bleeding, blood transfusions and other complications. Results. Eighty patients were treated preoperatively with enoxaparin, and 67 patients with fondaparinux. There was no significant difference in postoperative bleeding (532 +/- 355 for enoxaparin group vs. 580 +/- 300 ml for fondaparinux group, p = ns) or transfusion needs for the two groups. A subgroup analysis of the fondaparinux group showed a significantly higher amount of postoperative bleeding after 12 h for patients when preoperative treatment with fondaparinux was discontinued less than 36 h prior to surgery compared to more than 36 h. Discussion. This study suggests that preoperative treatment with fondaparinux for NSTE-ACS is as safe as enoxaparin in terms of postoperative bleeding and transfusion needs. Findings support discontinuation of fondaparinux at 36 h prior to surgery

Whole-genome sequencing based on formalin-fixed paraffin-embedded endomyocardial biopsies for genetic studies on outcomes after heart transplantation

Background Whole-genome sequencing (WGS) of heart transplant recipient- and donor-derived cardiac biopsies may facilitate organ matching, graft failure prediction, and immunotolerance research. The objective of this study was to determine the feasibility of WGS based on formalin-fixed paraffin-embedded endomyocardial biopsies. Methods and results The study included serial donor- and recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. DNA extraction and WGS were conducted. Additional WGS sequencing quality metrics and coverage were obtained with the Genome Analysis Toolkit (GATK). 455 endomyocardial samples from 37 heart transplant recipients were acquired from routine rejection monitoring and stored as formalin-fixed paraffin-embedded samples. They were analyzed after 3–26 years of storage. DNA was extracted from 114 samples and WGS was run on 85 samples. DNA extraction yielded 313 ng (IQR 96–601) for all samples. A coverage of 11.3x (IQR 9.0–15.9) was recorded for all WGS samples. Three samples stored for > 25 years yielded a coverage of > 25x. Data were generated for 1.7 billion reads per sample (IQR 1.4–2.7). A Transition/Transversion (TiTv) ratio of 2.09 ± 0.05 was calculated for all WGS samples. No associations were found among storage time, DNA yield, or sequencing quality metrics. Conclusions The present study demonstrated the feasibility of whole-genome sequencing based on endomyocardial biopsies. This process could enable large-scale retrospective genomic studies using stored histopathological samples

Methods for isolation and transcriptional profiling of individual cells from the human heart

Background: Global transcriptional profiling of individual cells represents a powerful approach to systematically survey contributions from cell-specific molecular phenotypes to human disease states but requires tissue-specific protocols. Here we sought to comprehensively evaluate protocols for single cell isolation and transcriptional profiling from heart tissue, focusing particularly on frozen tissue which is necessary for study of human hearts at scale. Methods and results: Using flow cytometry and high-content screening, we found that enzymatic dissociation of fresh murine heart tissue resulted in a sufficient yield of intact cells while for frozen murine or human heart resulted in low-quality cell suspensions across a range of protocols. These findings were consistent across enzymatic digestion protocols and whether samples were snap-frozen or treated with RNA-stabilizing agents before freezing. In contrast, we show that isolation of cardiac nuclei from frozen hearts results in a high yield of intact nuclei, and leverage expression arrays to show that nuclear transcriptomes reliably represent the cytoplasmic and whole-cell transcriptomes of the major cardiac cell types. Furthermore, coupling of nuclear isolation to PCM1-gated flow cytometry facilitated specific cardiomyocyte depletion, expanding resolution of the cardiac transcriptome beyond bulk tissue transcriptomes which were most strongly correlated with PCM1+ transcriptomes (r = 0.8). We applied these methods to generate a transcriptional catalogue of human cardiac cells by droplet-based RNA-sequencing of 8,460 nuclei from which cellular identities were inferred. Reproducibility of identified clusters was confirmed in an independent biopsy (4,760 additional PCM1- nuclei) from the same human heart. Conclusion: Our results confirm the validity of single-nucleus but not single-cell isolation for transcriptional profiling of individual cells from frozen heart tissue, and establishes PCM1-gating as an efficient tool for cardiomyocyte depletion. In addition, our results provide a perspective of cell types inferred from single-nucleus transcriptomes that are present in an adult human heart

Systemic effects of carbon dioxide insufflation technique for de-airing in left-sided cardiac surgery.

OBJECTIVE: Systemic effects of carbon dioxide (CO(2)) insufflation during left-sided cardiac surgery were evaluated in a prospective randomized study, with regard to acid-base status, gas exchange, cerebral hemodynamics, and red blood cell morphology. METHODS: Twenty patients undergoing elective left-sided cardiac surgery were randomized to de-airing procedure either by CO(2) insufflation technique (CO(2) group, n = 10) or by Lund technique without CO(2) insufflation (Lund group, n = 10). Groups underwent assessment of acid-base status by intermittent arterial blood gases and in-line blood gas monitoring. Capnography was used to determine volume of CO(2) produced. Cerebral hemodynamics was measured by transcranial Doppler sonography and near-infrared spectroscopy. Red cell morphology from cardiotomy suction and vent tubing was studied by scanning electron microscopy. RESULTS: Patients in the CO(2) group consequently developed significantly higher levels of hypercapnia with a concomitant increase in the volume of CO(2) produced despite significantly higher oxygenator gas flows compared with the Lund group. Effects on cerebral hemodynamics were observed in the CO(2) group with significantly higher blood flow velocities in the middle cerebral artery and higher regional cerebral saturation. Red blood cell damage was observed in the CO(2) group by scanning electron microscopy (97% in CO(2) group vs 18% in Lund group). CONCLUSIONS: Insufflation of CO(2) into the cardiothoracic wound cavity during left-sided cardiac surgery can induce hypercapnic acidosis and increased cerebral blood flow and local blood cell damage. These systemic effects should be monitored by in-line capnography and acid-base measurements for early and effective correction by increase in gas flows to the oxygenator

Pulmonary collapse alone provides effective de-airing in cardiac surgery: a prospective randomized study.

We previously described and showed that the method for cardiac de-airing involving: (1) bilateral, induced pulmonary collapse by opening both pleurae and disconnecting the ventilator before cardioplegic arrest and (2) gradual pulmonary perfusion and ventilation after cardioplegic arrest is superior to conventional de-airing methods, including carbon dioxide insufflation of the open mediastinum. This study investigated whether one or both components of this method are responsible for the effective de-airing of the heart

Comparison of the effectiveness and safety of a new de-airing technique with a standardized carbon dioxide insufflation technique in open left heart surgery: A randomized clinical trial.

OBJECTIVE: We have compared the effectiveness, time required for de-airing, and safety of a newly developed de-airing technique for open left heart surgery (Lund technique) with a standardized carbon dioxide insufflation technique. METHODS: Twenty patients undergoing elective open aortic valve surgery were randomized prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide insufflation technique (carbon dioxide group, n = 10). Both groups were monitored intraoperatively during de-airing and for 10 minutes after weaning from cardiopulmonary bypass by transesophageal echocardiography and online transcranial Doppler for the severity and the number of gas emboli, respectively. The systemic arterial partial pressure of carbon dioxide and pH were also monitored in both groups before, during, and after cardiopulmonary bypass. RESULTS: The severity of gas emboli observed on transesophageal echocardiography and the number of microembolic signals recorded by transcranial Doppler were significantly lower in the Lund group during the de-airing procedure (P = .00634) and in the first 10 minutes after weaning from cardiopulmonary bypass (P = .000377). Furthermore, the de-airing time was significantly shorter in the Lund group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of cardiopulmonary bypass was significantly lower in the carbon dioxide group (P = .00351), corresponding to significantly higher arterial partial pressure of carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398) in the oxygenator throughout the entire period of cardiopulmonary bypass. CONCLUSIONS: The Lund de-airing technique is safer, simpler, and more effective compared with the carbon dioxide insufflation technique. The technique is also more cost-effective because the de-airing time is shorter and no extra expenses are incurred

Pharmacometabolomic Profiling Of The General Population: Relation Of Active Metabolite Levels To Cardiovascular Risk Factor Control And Manifest Atherosclerosis

Introduction: The use of medications in the general population has increased over time. Information on active metabolite concentrations for common drugs in the general population is limited. Recent advances in metabolomic technologies have made high-throughput profiling of many active metabolites in large epidemiological cohorts increasingly feasible.Aim: 1. Prospective assessment of the proportion of measurable active metabolite levels of major drugs in the general population using mass spectrometry. 2. Relation of cardiovascular (CV) drugs with inadequate risk factor control and CV disease.Methods: Assessment of CV risk factors by coronary CT angiography and carotid ultrasound imaging in a large prospective cohort of 6,251 individuals randomly selected from the general population in Malmö, Sweden (age 50-64 years). Untargeted metabolomic profiling of fasting plasma was performed by Metabolon, USA in a random subset of 3,986 subjects.Results: Intake of at least one prescribed drug was reported in 1840 subjects (46%). Combination drugs were reported in 249 subjects (6%). The most common drug classes reported were lipid-lowering (n=369, 9% of which most were statins), beta blockers (n=307, 8%), ARB (n=272, 7%), and ACE inhibitors (268, 7%), followed by levothyroxine, CCB, antidepressants, glucocorticoids, PPI, antidiabetic, bronchodilators and diuretics. For major CV drugs, detectable active metabolite levels ranged from 54% (atorvastatin and enalapril) to 96% (metoprolol and metformin). Non-detectable levels of lipid-lowering, antihypertensive, and antidiabetic drugs were associated with higher LDL, cholesterol, BP and glucose, although only antidiabetic drugs were significant (p<0.05). Non-detectable levels of lipid-lowering and antihypertensive drugs were also non-significantly associated with increased coronary calcium and carotid plaque.Conclusion: Our study provides an overview of the distribution of common drugs with detectable levels in a contemporary Swedish population. Pharmacometabolomic profiling revealed that non-measurable levels of common CV drugs were associated with lower risk factor control and non-significant trends towards more atherosclerotic disease by imaging in a substantial number of subjects