Functional mitral regurgitation: a 30-year unresolved surgical journey from valve replacement to complex valve repairs.

Functional mitral regurgitation remains one of the most complex and controversial aspect--for both clinicians and surgeons--in the management of mitral valve disease in the context of left ventricular dysfunction. Given the current absence of clear guidelines, as well as of results from randomized trials comparing the outcome of different surgical strategies potentially available for this complex scenario, surgical decision making for these high-risk patients poses a real dilemma in the daily practice. The resulting surgical choices often represent a questionable combination of surgeons' personal feeling, local supplies, patients' life expectancy and risk/benefit ratios, opinions and statements of the experts, and so on. This review provides an overview of the present knowledge about the complex pathophysiology underlying functional mitral regurgitation, the different pathophysiology-guided surgical techniques suggested in the last decades, as well as the current results following these different surgical techniques.

Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval shunt.

Pulmonary arterial hypertension is a common complication of congenital heart defects with left-to-right shunts. Current preclinical models do not reproduce clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval shunt was firstly described as a model of right ventricle volume overload. The pathophysiology and the possible determination of pulmonary arterial hypertension of different periods of shunt exposure are still undefined. A method to create standardized, reproducible aorto-caval shunt was developed in growing rats (260±40 g). Three groups of animals were considered: shunt exposure for 10 weeks, shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and magnetic resonance revealed increased right ventricular end diastolic area in shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated increased right ventricular afterload and increased effective pulmonary arterial elastance (Ea) in shunt at 20 weeks compared to control (1.29±0.20 vs. 0.14±0.06 mmHg/µl, p=0.004). At the same time point, the maximal slope of end-systolic pressure-volume relationship (Ees) decreased (0.5±0.2 mmHg/ml vs. 1.2±0.3, p<0.001). Consequently, right ventricular-arterial coupling was markedly deteriorated with a ≈50% decrease in the ratio of end-systolic to pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished (≈30% decrease in left ventricular end-diastolic volume). Histology demonstrated medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto-caval shunt is a reliable model to produce right ventricular volume overload and secondary pulmonary arterial hypertension. This model could be an alternative with low mortality and high reproducibility for investigators on the underlying mechanisms of shunt-related pulmonary hypertension.

First-time, isolated surgical aortic valve replacement after prior coronary artery bypass surgery: results from the RECORD multicenter registry.

BACKGROUND: This multicenter study was undertaken to determine the immediate and long-term outcomes in patients undergoing a primary surgical aortic valve replacement (AVR) who had a previous coronary artery bypass graft surgery with patent grafts. METHODS: One hundred and thirteen consecutive patients (mean EuroSCORE II, 10.3 ± 7.7%, median 8.0%) who underwent first-time isolated AVR after coronary artery bypass grafting (CABG) were the subjects of this multicenter study. The procedure was performed through a full sternotomy in 95.7% of cases, a patent internal mammary artery graft was clamped in 76.6% of patients. The temperature of cardioplegia was ≤12 °C in 62.8% of patients and systemic temperature was <32 °C in 23.9% of patients. RESULTS: Thirty-day mortality was 4.4%. Stroke was observed in 8.0% of patients, low cardiac output syndrome in 14.1%, prolonged tracheal intubation in 20.8%, and intensive care unit stay was longer than five days in 19.5% of patients. Among patients with a patent internal mammary graft (91 patients), clamping of this graft (5.7% vs. 0%, p = 0.57) was associated with a nonsignificant trend toward increased 30-day mortality. One-, three- and five-year survival rates were 91.5%, 90.4%, and 88.4%, respectively. CONCLUSIONS: Patients undergoing isolated AVR after prior CABG have a good immediate and late survival. A history of prior CABG should not be considered an absolute indication for transcatheter AVR.

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest.

INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 µg/kg/min; n = 15), epinephrine (0.1 µg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS: The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.

Targeting urocortin signaling pathways to enhance cardioprotection: is it time to move from bench to bedside?

Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology.

Comparison between D901 Lilliput 1 and Kids D100 neonatal oxygenators: toward bypass circuit miniaturization.

Progress in biomaterial technology and improvements in surgical and perfusion strategy ameliorated morbidity and mortality in pediatric cardiac surgery. In this study, we describe our clinical experience comparing performance of two neonatal oxygenators. From January 2002 to March 2011, 159 infants with less than 5 kg body weight underwent heart surgery. Ninety-four patients received a D901 Lilliput 1 oxygenator with standard bypass circuit (group A), while 65 received a D100 Kids with miniaturized bypass circuit (group B). Miniaturization consisted in shortened arterial, venous, cardioplegia, and pump-master lines. Priming composition consisted in Ringer's acetate solution with addition of albumin and blood, with target hematocrit of 24% or greater. In group B cardiopulmonary bypass (CPB) was vacuum-assisted and started with an empty venous line. Modified ultrafiltration and Cell-Saver blood infusion was routinely applied in both groups. Average ± standard deviation (SD) age at repair was 37 ± 38 days in group A and 59 ± 60 days in group B (P = 0.005). Average ± SD weight, height, and body surface area were 3.5 ± 0.7 kg, 52 ± 4 cm, and 0.22 ± 0.03 m(2) , respectively, in group A, and 3.7 ± 1 kg, 53 ± 5 cm, and 0.23 ± 0.02 m(2) , respectively, in group B (P = not significant [NS]). Male sex was predominant (55 vs. 58%, P = NS). Priming volume was 524 ± 67 mL (group A) and 337 ± 53 mL (group B) (P = 0.001). There were no statistical differences in hemoglobin at the start, during, and at the end of CPB, but group A required higher blood volume added to the prime (111 ± 33 vs. 93 ± 31 mL, P = 0.001). In group B, two surgical procedures were completed in total hemodilution. In group B, CPB time and aortic cross-clamp time were shorter than in group A (106 ± 52 vs. 142 ± 78 min and 44 ± 31 vs. 64 ± 31 min, respectively, P = 0.001). There were 16 hospital deaths in group A and 4 in group B (P = 0.04). Durations of mechanical ventilation and intensive care unit stay were 5.3 ± 3.2 vs. 4.1 ± 3.2 days (P = 0.02) and 6.5 ± 4.9 vs. 5.1 ± 3 days (P = 0.03), respectively. There were significant differences in inotropic score (1083 ± 1175 vs. 682 ± 938, P = 0.04) and blood postoperative transfusion (153 ± 226 vs. 90 ± 61 mL, P = 0.04). Twenty-seven patients in group A and 10 in group B presented with major adverse postoperative complications (P = 0.04). Use of neonatal oxygenators with low priming volume, associated with a miniaturized bypass circuit, seems to be a favorable strategy to decrease postoperative morbidity after cardiac surgery in neonates and infants.

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.

Effects of angiotensin II type 1 receptor antagonist and temperature on prolonged cardioplegic arrest in neonatal rat myocytes.

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P < 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1ß (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants.

Renal cell carcinoma with invasion of the tricuspid valve apparatus.

A right atrial in-growth of renal carcinoma occurs in 1% of cases. A traditional approach to removal of the tumor using cardiopulmonary bypass (CPB) and deep-hypothermic circulatory arrest (DHCA) has been challenged in favor of techniques that allow tumor removal without CPB and DHCA. To the best of the present authors' knowledge, no report has yet been made of an invasion by the tumor of the tricuspid valve leaflets and subvalvular apparatus. The details of such a case are reported herein, where CPB + DHCA was used to completely remove the neoplasm, and to preserve tricuspid valve competence.

Clinical evaluation of new generation oxygenators with integrated arterial line filters for cardiopulmonary bypass.

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group-T) or Sorin Synthesis (40 patients, Group-S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High-sensitivity C-reactive protein (hs-CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between-groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group-P and group*time-P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group-T showed higher hs-CRP (group-P = 0.034), aPTT (group-P = 0.0001), and INR (group-P= 0.05), with lower serum albumin (group-P = 0.014), total proteins (group-P = 0.0001), fibrinogen (group-P = 0.041), and PLTs (group-P = 0.021). Group-T also showed higher postoperative bleeding (group-P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post-CPB inflammatory response.

Left ventricular remodeling, hemodynamics and early clinical outcomes after aortic valve replacement with the Pericarbon Freedom stentless bioprosthesis: results from the Italian Prospective Multicenter Trial.

BACKGROUND AND AIM OF THE STUDY: The aims of this multicenter prospective observational trial were to evaluate: (i) the left ventricular remodeling, hemodynamics and early clinical outcomes of patients undergoing aortic valve replacement (AVR) with the Pericarbon Freedom (PF) stentless bioprosthesis; and (ii) the impact of the two suture techniques--continuous and interrupted--on the hemodynamic performance of the bioprosthesis. METHODS: Between November 2001 and April 2004, a total of 226 patients (131 females, 95 males; mean age 73.2 +/- 8.8 years) underwent AVR with the PF valve (Sorin Group, Saluggia, Italy) at eight Italian cardiac surgery centers. Associated surgery was performed in 73 patients (32%); of these operations, 54 were coronary artery bypass grafting. A continuous-suture technique was used in 132 patients (58%), and an interrupted-suture in 90 (40%). The suture technique was not available for four patients. All patients underwent clinical and echocardiographic evaluation immediately before surgery, and at one, six, and 12 months thereafter. The median follow up was 380 days (Q1: 363 days; Q3: 410 days), and the total cumulative follow up 236.9 patient-years (pt-yr). RESULTS: The overall 30-day mortality was 3.5% (n = 8). Late deaths occurred in 10 patients (4%/pt-yr), of which three were valve-related (1%/pt-yr). The overall and valve-related survivals at one year were 92 +/- 2% and 98 +/- 1%, respectively. Freedom from structural valve deterioration, endocarditis, reoperation and thromboembolic events was 100%, 93 +/- 1%, 98 +/- 1% and 99 +/- 1% at one year, respectively. The peak and mean transprosthetic gradients at one year were: 19.7 +/- 12.27 and 8.7 +/- 6.0 mmHg, respectively. After 12 months, significant reductions (compared to preoperative) were observed in the left ventricular mass (148.5 +/- 48.8 versus 194.4 +/- 54.6 g/m2; p < 0.001) and mean wall thickness (1.08 +/- 0.19 versus 1.32 +/- 0.23 cm; p < 0.001). The continuous-suture technique showed a trend towards lower postoperative gradients than did the interrupted-suture technique. CONCLUSION: The data obtained indicated that the PF bioprosthesis provided excellent results in terms of left ventricular mass regression, hemodynamics, and early clinical outcome. Although a trend towards a better hemodynamic performance of the continuous-suture technique was observed, this aspect requires further evaluation.

Aortic root physiology late after a "perfect" ross operation: magnetic resonance imaging study of three operative techniques.

In order to define physiological properties of the autograft root, magnetic resonance imaging (MRI) findings relative to three different operative techniques were compared with those of control subjects. Twenty-three patients, 18/5 M/F, aged 32 ± 9 years, underwent MRI assessment of the aortic root. Patients with normally functioning autograft valve and at least 4 years of follow-up (average 5.6 ± 1.9, range 4-10 years) were selected for each technique: six subcoronary (Group 1), nine inclusion (Group 2), and eight freestanding root (Group 3). Results were compared among patient groups and with seven control subjects, 6/1 M/F, aged 30 ± 2 years (P = ns). Morphological and functional properties were defined using transverse and paracoronal views, during systole and diastole. Mean aortic size in each group was greater than control, except for the LV-aortic junction and the sinus of Valsalva in Group 1 (26 ± 5 vs. 23 ± 3 mm, P = 0.2 and 33 ± 6 vs. 30 ± 5 mm, P = 0.3). Aortic valve plane rotation (P = 0.02) and root dilatation (P = 0.02) were more common in Group 3. Altered valve opening dynamics and asymmetrical aortic flow profile were also more common in Group 2 (P = 0.03) and Group 3 (P = 0.04). Distensibility was significantly reduced at sinus level in Group 2 and 3 compared with control (4.1 ± 3.5% and 3.6 ± 4.4% vs. 9.0 ± 4.7%, P = 0.03). Asymmetrical aortic flow profile was more common in patients with aortic dilatation (P = 0.05) and with severely reduced (<4%) root elasticity (P = 0.06). Among the three techniques, only subcoronary grafting allows preservation of physiological autograft valve dynamics, aortic flow and distensibility, at all root levels, late after operation. These findings may have relevant implications in the selection of the ideal Ross technique.

Rescue extracorporeal life support for acute verapamil and propranolol toxicity in a neonate.

Extracorporeal life support (ECLS) to manage acute antiarrhythmic drugs toxicity in neonates has never been reported. Here presented is a case of venoarterial extracorporeal membrane oxygenation support in a newborn with refractory low cardiac output as a result of acute Ca-channel and ß-receptor antagonist toxicity for treatment of paroxysmal supraventricular tachycardia (SVT). Shortly after onset of ECLS, the baby recovered sinus rhythm and subsequent bouts of SVT were controlled by amiodarone infusion and repeated DC shocks. Weaning was possible on the 5th day after implant, once recovery of the left ventricular function and optimization of the antiarrhythmic medication were achieved. In neonates with severe but potentially reversible cardiac dysfunction caused by drug toxicity, ECLS can maintain cardiac output and vital organ perfusion while allowing time for drug redistribution, metabolism, and clearance.

Effects of intra-aortic balloon pump on coronary artery bypass grafts blood flow: differences by graft type and coronary target.

The intra-aortic balloon pump (IABP) is used worldwide as an anti-ischemic strategy. However, little is known about the modifications of the graft blood flow during IABP. A retrospective study aimed at analyzing transit-time flow measurements during 1:1 IABP and during its cessation in 401 consecutive patients receiving IABP before coronary artery bypass grafting (n = 880 graft segments) was reported. All normally functioning grafts were considered. Mean diastolic and mean blood flow improved significantly during 1:1 IABP compared with during IABP cessation (P < 0.001), although mean and end-diastolic arterial pressures were significantly lower (P = 0.001). Arterial and sequential saphenous vein (SV) grafts showed greater improvements in mean diastolic and mean flow compared with single venous grafts. Higher flows were also observed in the grafts directed to the circumflex territory. Surplus graft flow (SGF, defined as mean flow during 1:1 IABP/mean flow with IABP off) was recruited (SGF >1) during 1:1 IABP, with higher values in single arterial or sequential SV grafts versus single venous grafts (both P < 0.001). Y-conduit radial artery (RA) grafts showed higher maximum diastolic flow, mean flow, and SGF compared to aortocoronary RA or SV grafts. In this retrospective analysis, IABP was associated with improved diastolic and mean blood flow in bypass grafts. Arterial, sequential, and Y-conduit grafts were associated with greater improvements in blood flow and SGF than aortocoronary SV grafts.

Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates <2.0 kg). A cardioplegia delivery system was inserted into the aortic root. Under moderate hypothermia, ascending and descending aorta were cross-clamped, and "beating heart and brain" aortic arch repair was performed. Arch repair was composed of patch augmentation in five, end-to-side anastomosis in three, and replacement in two patients. Average cardiopulmonary bypass time was 163 ± 68 min (71-310). In two patients only (one HLHS, one complex single ventricle), a period of cardiac arrest was required to complete intracardiac repair. In such cases, antegrade blood cardioplegia was delivered directly via the same catheter used for selective myocardial perfusion. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 39 ± 18 min (17-69). Weaning from cardiopulmonary bypass was achieved without inotropic support in three and with low dose in seven patients. One patient required veno-arterial extracorporeal membrane oxygenation. Four patients, body weight <3.0 kg, needed delayed sternal closure. No neurologic dysfunction was noted. Renal function proved satisfactory in all, while liver function was adequate in all but one. The present experience suggests that selective and independent cerebro-myocardial perfusion is feasible in patients with complex or recurrent aortic arch disease, starting from premature newborn less than 2.0 kg of body weight to adults. The technique is as safe as previously reported methods of cerebro-myocardial perfusion and possibly more versatile.

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1ß (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart.

Veno-venous extracorporeal membrane oxygenation as a bridge to and support for pulmonary thromboendarterectomy in misdiagnosed chronic thromboembolic pulmonary hypertension.

Diagnostic delay in patients suffering massive pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) has inevitably fatal consequences. Indications to pulmonary thromboendarterectomy (PTE) and extracorporeal membrane oxygenation (ECMO) are limited by severe comorbid conditions, some of which, as neurologic disease, absolutely contraindicate these procedures. We reported the clinical course of a severely diseased patient with a history of meningitis, psychosis and epilepsy, experiencing acute massive pulmonary embolism complicated by acute respiratory failure, successfully treated by ECMO and PTE. A 51-year-old woman with massive PE complicating a misdiagnosed CTEPH needed mechanical ventilation because of acute respiratory insufficiency. Thoracic computed tomography (CT) scan demonstrated PE, and brain CT showed multiple cerebral and cerebellar ischemic lesions. Veno-venous ECMO assistance was instituted despite CT imaging. She recovered from acute respiratory insufficiency by means of veno-venous ECMO. Weaning from ECMO was however impossible until surgical exploration demonstrated an underlying chronic CTEPH, which was successfully addressed by PTE, switching the ECMO system to a standard cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged home in healthy condition. Despite the fact that the cost-effective ratio should always be considered in advanced life support, expanding the commonly accepted selection criteria for expensive procedures might be advisable in selected acute life-threatening cases, in view of the possibility to unexpectedly save lives.

Spontaneous rupture of the right sinus of valsalva mimicking an ascending aortic intramural hematoma.

Spontaneous ruptures of the ascending aorta are extremely rare and require emergent surgical intervention. We report a case of a delayed diagnosis of a spontaneous, localized periostial rupture of a nondilated right sinus of Valsalva, which mimicked an intramural hematoma of the ascending aorta. The diagnosis and surgical management of this unusual pathology is the subject of this case report.

Unusual association of left ventricular diverticulum and hypertrophic cardiomyopathy in an adult.

A 68-year-old female with hypertrophic obstructive cardiomyopathy (HOCM), fibrous subaortic stenosis, mitro-aortic valve insufficiencies, and congenital left ventricular diverticulum (CLVD) at apical level was diagnosed after syncope. Although the association between HOCM and CLVD has been previously reported, no case has ever been disclosed in advanced adulthood.

Vincenzo Gallucci: Memories of a Surgeon, Scientist, and Teacher.

Thirty years ago, Vincenzo Gallucci, MD, head of the Cardiovascular Surgery Institute of the University of Padua Medical School in Italy, died in a car accident at the age of 55 years. Vincenzo Gallucci was one of the most authoritative Italian cardiac surgeons, a fine, gentle, and extremely talented surgeon. He is credited with the first implant of a glutaraldehyde-fixed, stented porcine Hancock bioprosthesis in 1970 and with the first orthotopic heart transplantation performed in Italy in 1985. After 30 years, the memory of a great surgeon, scientist, and teacher is still alive, particularly in those who received his important heritage.