Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity.

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study's aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation.

Early Postoperative Thrombosis of Transcatheter Aortic Valve-in-Valve Prosthesis.

Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has been popularized as an attractive alternative to redo surgical aortic valve replacement for bioprosthetic valve dysfunction. Acute valve thrombosis has been occasionally described after ViV-TAVR. Lack of anticoagulant therapy has been always considered a crucial risk factor. This report describes a rare case of early postoperative fatal ViV-TAVR thrombosis despite adequate anticoagulation in addition to dual antiplatelet therapy.

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

Pulsatile cardiopulmonary bypass and renal function in elderly patients undergoing aortic valve surgery†.

OBJECTIVES: To evaluate if pulsatile cardiopulmonary bypass (CPB) has any protective influence on renal function in elderly patients undergoing aortic valve replacement (AVR). METHODS: Forty-six patients (≥ 75 years old) with aortic valve stenosis underwent AVR with either pulsatile perfusion (PP) or non-pulsatile perfusion (NP) during CPB. Haemodynamic efficacy of the blood pump during either type of perfusion was described in terms of the energy equivalent pressure and the surplus haemodynamic energy. Urine samples were collected before surgery, at sternum closure, and at 2 and 18 h of intensive care unit stay to detect acute kidney injury markers. Perioperative urine levels of N-acetyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (NGAL) were assessed together with plasma creatinine, creatinine clearance (CCr) and 24-h haemodynamic monitoring. Normally distributed continuous variables were described as mean ± standard deviation and non-normally distributed data were presented as the median [25th-75th percentiles]. RESULTS: PP was characterized by a significantly higher amount of surplus haemodynamic energy transferred to the patients (P < 0.001), with lower mean systemic vascular resistance during CPB (P = 0.020) and during 18 h postoperatively (group-P = 0.018). No difference was found between pre- and postoperative CCr in the PP group (71 ± 23 vs 60 ± 35 ml/min, P = 0.27), while its statistically significant perioperative decrement was observed in the NP group (67 ± 24 vs 45 ± 15 ml/min, P < 0.001). The PP group showed significantly lower urinary levels of NAG at 18 h postoperatively (P = 0.008), and NGAL at sternum closure (P = 0.010), 2 h (P < 0.001) and 18 h (P = 0.015) postoperatively. CONCLUSIONS: Short-term PP in elderly patients showed higher safety for renal physiology than NP, resulting in better maintenance of glomerular filtration and lower renal tissue injury.

The effect of pulsatile cardiopulmonary bypass on lung function in elderly patients.

PURPOSE: Cardiopulmonary bypass is still a major cause of lung injury and delay in pulmonary recovery after cardiac surgery. Although it has been shown that pulsatile flow induced by intra-aortic balloon pumping is beneficial for preserving lung function, it is not clear if the same beneficial effect can be accomplished with pulsatile flow generated in the extracorporeal circuit. Therefore, we investigated the effect of pulsatile flow, produced by a centrifugal pump, on lung function in elderly patients. METHODS: Serial measurements of lung biomarkers Clara cell 16 kD protein, surfactant protein D, and elastase were performed on blood samples from 37 elderly patients (≥75 years) who underwent elective aortic valve replacement surgery with CPB, either with pulsatile perfusion or continuous perfusion. Pulmonary function was assessed by postoperative ventilation time, the arterial blood oxygenation (PaO2/FiO2), the alveolar-arterial oxygen gradient (Aa-O2 gradient) and the pulmonary vascular resistance indexed by body surface area (PVRi). RESULTS: There was no difference in lung function between both groups, as assessed by the postoperative ventilation time, the PaO2/FiO2 ratio, and the Aa-O2 gradient. The PVRi, however, was significantly lower in the pulsatile perfusion group 15 mins after the administration of protamine (p<0.05). The plasma concentrations of the lung biomarkers increased during surgery and peaked at 1 h ICU, there were however no differences between groups. CONCLUSIONS: Pulsatile flow does not seem beneficial to postoperative lung function in elderly patients. Moreover, pulsatile flow does not affect lung function on a subclinical level as assessed by lung biomarkers.

Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) has a risk of embolic injury with an important role of gaseous micro-bubbles (GMBs), coming from CPB-circuit. Pulsatile perfusion (PP) can provide specific conditions for supplementary GMB-activity with respect to non-pulsatile (NP). We aimed to test GMB-filtering properties of three modern oxygenators under pulsatile and non-pulsatile conditions. METHODS: Seventy-eight patients undergoing on-pump myocardial revascularization were randomized prospectively into three equal groups according to the oxygenator model used during CPB. Terumo Capiox-FX25, Sorin Synthesis or Maquet Quadrox-i-Adult membrane oxygenators were tested. Each group was divided equally to undergo PP or NP. GMBs were counted by means of a GAMPT-BCC200 bubble-counter with two probes placed at preoxygenator and arterial post-filter positions. Results were evaluated in terms of GMB-volume, GMB-number, amount of large over-ranged GMBs, a series of filtering indices and major neurological outcomes. RESULTS: PP decreased GMB-filtering properties of the tested oxygenators. Those with integrated filters (CAPIOX-FX25 and SYNTHESIS) did not show significant differences between perfusion groups, while QUADROX-i oxygenator with external arterial filter showed significantly higher GMB-volume (P < 0.001), GMB-number (P < 0.001) and amount of over-ranged bubbles (P < 0.001) detected in arterial line during PP. Despite the differences in filtering capacity of all circuits with both types of perfusion, no important differences in clinical outcomes and major neurological events were observed. CONCLUSIONS: Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during CPB. PP requires specially designed circuit components to avoid the risk of additional GMB delivery.

Gaseous micro-emboli activity during cardiopulmonary bypass in adults: pulsatile flow versus nonpulsatile flow.

Cardiopulmonary bypass (CPB) has a risk of cerebral injury, with an important role of gaseous micro-emboli (GME) coming from the CPB circuit. Pulsatile perfusion is supposed to perform specific conditions for supplementary GME activity. We aimed to determine whether pulsatile CPB augments production and delivery of GME and evaluate the role of different events in GME activity during either type of perfusion. Twenty-four patients who underwent on-pump coronary artery bypass grafting surgery at the University of Verona were divided equally into two groups-pulsatile perfusion (PP) group and nonpulsatile perfusion (NP) group. The circuit included a JostraHL-20 roller pump set in pulsatile or nonpulsatile mode, an open Sorin Synthesis membrane oxygenator with integrated screen-type arterial filter, and phosphorylcholine-coated tubes. Hemodynamic flow evaluation was performed in terms of energy equivalent pressure and surplus hemodynamic energy (SHE). GME were counted by means of a GAMPT BCC200 bubble counter (GAMPT, Zappendorf, Germany) with two probes placed at postpump and postarterial filter positions. Results were evaluated in terms of GME number, GME volume, number of over-ranged GME from both probes, and series of filtering indexes. In PP mode, the pump produced and delivered along the circuit significantly higher amounts of SHE than in NP mode. At the venous postpump site, GME number was significantly higher during PP but no difference was found in terms of GME volume or number of over-ranged bubbles. No significant difference in GME number, GME volume, or number of over-ranges was found at the postarterial filter site. Filtering indexes were similar between the two groups. Neither type of perfusion was shown to contribute to excessive GME production during the most important perfusionist manipulation. Pulsatility leads to GME increment by splitting and size diminishing of the existing bubbles but not by additional gas production. PP augmented GME number at the venous postpump site, while mean volume remained comparable with NP. Sorin Synthesis oxygenator showed high efficacy in GME removal during either type of perfusion. Supplementary GME production and delivery during typical perfusionist manipulations did not depend on perfusion type.

The Sorin freedom stentless pericardial valve: clinical and echocardiographic performance at 10 years.

OBJECTIVE: The Sorin Pericarbon Freedom (SPF) is a stentless valve made of pericardium clinically available in 1990. We report the clinical and hemodynamic performance of the SPF at 10 years. METHODS: From April 2000 to December 2005, 85 patients with a mean age of 75 ± 6 years (range 57-86), underwent aortic valve replacement (AVR) with an SPF. Mean left ventricular ejection fraction was 58 ± 10% (range 29-86%) and mean peak transvalvular gradient (PG) 86 ± 24 mmHg. Clinical evaluation was performed at 3, 6, 12 months, and yearly thereafter. RESULTS: There were 2 operative deaths (2.4%). Follow-up ranged from 2 to 135 months (mean 78 ± 32 months) and was 99% complete. There were 35 late deaths, 7 of which were valve-related, with an actuarial survival of 45 ± 8% at 10 years. Structural SPF deterioration occurred in 2 patients, with an actuarial freedom of 96 ± 3%. A total of 4 patients were re-operated, 2 because of structural deterioration, 1 because of endocarditis, and 1 because of sinotubular junction dilatation; freedom from reoperation was 93 ± 4% at 10 years. At last clinical control, 41 patients (89%) were in NYHA class I or II. Mean SPF effective orifice area varied from 1.55 ± 0.66 cm2 for size 21 mm to 2.33 ± 0.86 cm2 for size 27 mm; PG varied from 19 ± 10 mmHg for size 21 mm to 11 ± 6 mmHg for size 27 mm. Left ventricular mass index decreased from 213 ± 51 gm/m2 to 157 ± 436 gm/m2 (p<0.001). CONCLUSIONS: The SPF has demonstrated overall good results in terms of valve durability and freedom from valve-related complications up to 10 years, with excellent hemodynamic performance.

Prognostic value of myocardial fibrosis in patients with severe aortic valve stenosis.

OBJECTIVE: To evaluate whether myocardial fibrosis influences left ventricular performance in severe aortic stenosis and to assess its effect on long-term survival after aortic valve replacement. METHODS: Myocardial fibrosis was evaluated in biopsy specimens taken from the interventricular septum in 99 patients undergoing aortic valve replacement because of severe or prevalent aortic stenosis. Clinical and echocardiographic evaluations were performed at a mean follow-up of 6.2 ± 3.0 years. The patients were classified according to the myocardial fibrosis severity (none or mild in 28, moderate in 52, and severe in 19). RESULTS: Patients with severe myocardial fibrosis had a dilated left ventricle and positive association between the left ventricular end-diastolic diameter (R = 0.77, P < .001), left ventricular end-systolic diameter (R = 0.78, P < .001), left ventricular end-systolic wall stress (R = 0.74, P < .001) and the degree of myocardial fibrosis. Myocardial fibrosis was inversely related to left ventricular fractional shortening (R = -0.64, P < .001), left ventricular ejection fraction (R = -0.53, P < .001), and left ventricular relative wall thickness (R = -0.70, P < .001). Patients with a higher grade of myocardial fibrosis had a significantly lower freedom from cardiac death at 10 years (42% ± 19% vs 89% ± 6%, P = .002), with congestive heart failure the most common cause of death. At Cox regression analysis, patient age (P = .012), low preoperative transvalvular gradient less than 40 mm Hg (P = .040), preoperative end-systolic wall stress (P = .046), and preoperative myocardial fibrosis grade (P = .034) emerged as the strongest independent predictors of mortality. CONCLUSIONS: In patients with severe aortic valve stenosis, the amount of myocardial fibrosis appears to have significant effect on clinical status and long-term survival after aortic valve replacement. From these results, we believe that new strategies for the earlier detection of myocardial fibrosis are needed to achieve a better prognostic outcome.