The Ross full root replacement in adults with bicuspid aortic valve disease.

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve disease (BAVD) is the most common congenital cardiac lesion causing aortic stenosis in adults. This lesion can be associated with a histological abnormality of the aortic wall and dilated or aneurysmal ascending aorta. In younger patients, the Ross operation offers several advantages over conventional aortic valve replacement (AVR); however, the rationale of performing this procedure on adults in the face of BAVD have been questioned. METHODS: Between 1994 and 2009, a total of 101 adult patients (mean age 36 years; range: 18-61 years) with BAVD underwent the Ross full root replacement at the authors' institution. Of these patients, 23 (23%) had an aneurysmal ascending aorta (4.0-5.2 cm) associated with BAVD which was resected at the time of, or subsequent to, a Ross AVR. The end point of the study was freedom from Ross autograft dilatation > 4.0 cm, dysfunction, or valve repair or replacement. RESULTS: The mean follow up was 6.0 +/- 3.9 years. At the latest follow up, 19 patients (19%) had a dilated ascending aorta with a mean size 45.1 mm (range: 40-64 mm). Eight patients (8%) required a redo operation on the autograft. Three of seven patients undergoing reoperation had their autograft valve preserved; the remaining four underwent a modified Bentall root replacement. One patient had a repair of a left ventricular pseudoaneurysm below the Ross valve. Only three patients with preoperative ascending aorta dilation developed late autograft dilation. Freedom from autograft dilatation > 4.0 cm, dysfunction, repair or replacement was 80% at 10 years. CONCLUSION: Mid-term results indicate that Ross AVR in adults with BAVD had good outcomes, with a low incidence of autograft-related complications. In almost half of the patients undergoing reoperation, the autograft valve was preserved. The incidence of autograft valve insufficiency and dilatation might be further reduced by: (i) aggressively treating any postoperative systemic hypertension; (ii) externally fortifying the annulus and sinotubular junction of the autograft with Dacron strips; and/or (iii) replacing a dilated ascending aorta with a Dacron interposition graft. The preoperative diagnosis of BAVD and/or aneurysmal ascending aorta is not predictive of late autograft dilatation or failure.

Fate of the autograft and homograft following Ross aortic valve replacement: reoperative frequency, outcome, and management.

BACKGROUND AND AIM OF THE STUDY: The optimal hemodynamic performance and potential for growth of the pulmonary autograft has led to expanded indications for the Ross aortic valve replacement (AVR) procedure in some centers. The authors' institutional mid-term experience was reviewed to assess autograft and homograft hemodynamics, growth profile of the autograft, and reoperative frequency following Ross AVR. METHODS: Between June 1993 and June 2005, 167 consecutive patients (mean age 24.9 +/- 15.5 years; range: 1 month to 61 years) underwent Ross AVR: 48% of patients were aged < 19 years. Additional procedures (n = 78) were performed in 55 patients (33%) at the time of the Ross procedure. In total, 151 patients had isolated aortic valve disease and 16 pediatric patients had more complex, multi-level left ventricular outflow tract obstruction. RESULTS: There were two early deaths (1.2%) and one late death (0.6%) over a mean follow up of 5.1 +/- 3.0 years (range: 1 month to 11 years). Actuarial survival at 10 years was 98%. In pediatric patients with Konno procedure (n = 16), the pulmonary autograft mean annulus diameter increased from 10.2 to 19.9 mm. Twelve patients underwent 12 reoperations without mortality for autograft insufficiency or an ascending aortic aneurysm at a median interval of 5 years (range: 2 to 8 years): aortic annuloplasty and ascending aorta replacement (n = 4), composite aortic root replacement (n = 7), and repair of left ventricular pseudoaneurysm (n = 1). Freedom from replacement of the pulmonary autograft was 96% at 10 years. Five of the 164 surviving patients (3%) developed significant obstruction of the pulmonary homograft and required conduit replacement at a median of four years. CONCLUSION: The Ross AVR can be performed with good mid-term results, including the pediatric age group. The potential for development of significant autograft insufficiency and homograft stenosis warrants annual follow up through the intermediate and late terms.

Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease.

OBJECTIVES: We investigated whether pericardial levels of a pro-angiogenic factor (vascular endothelial growth factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collateral circulation in patients with significant coronary artery disease (CAD). BACKGROUND: Coronary collateralization favorably alters the prognosis of patients with occlusive CAD. The specific factors that mediate and maintain collateral formation in coronary vessel occlusion are yet to be identified. METHODS: Coronary angiograms from 39 patients undergoing coronary artery bypass surgery were evaluated for the absence of collaterals (n = 20) or the presence of Rentrop classification grade 3 collaterals (n = 19). Pericardial fluid samples were obtained at the time of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparing the two groups of patients. RESULTS: Vascular endothelial growth factor levels were not significantly different between the groups (28.86 +/- 4.67 pg/ml vs. 24.39 +/- 3.08 pg/ml, p = 0.43). However, pericardial fluid endostatin levels were nearly 40% lower in patients with grade 3 collateralization compared with those lacking angiographic evidence of collaterals (15.17 +/- 1.87 ng/ml vs. 24.25 +/- 2.08 ng/ml, p < 0.0025). CONCLUSIONS: Pericardial fluid levels of endostatin, but not VEGF, are associated with the presence or absence of collaterals in patients with CAD. These data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collateral formation.

Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia.

High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE) measurements of the left anterior descending (LAD) coronary artery wall thickness are larger than measurements obtained by intravascular ultrasound. We hypothesize that this difference is due to inclusion of the third vascular layer, which may represent adventitia by HR-2DTTE, and that this layer must be increasing in thickness with the development of atherosclerosis. We evaluated the contribution of this third layer to the wall thickness of the normal and atherosclerotic LAD artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE) as the reference standard. Eighteen patients (10 men, mean age 62 years), 13 with coronary atherosclerosis and 5 with normal coronary arteries, referred for open-heart surgery, underwent preoperative HR-2DTTE evaluation of the LAD artery (SONOS 5500; 3- to 8-MHz transducer) and intraoperative HFEE of the LAD artery (SONOS 5500; 6- to 15-MHz transducer). Wall thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries by both HR-2DTTE (1.9 +/- 0.3 vs 1.0 +/- 0.1 mm, p = <0.001) and HFEE (1.8 +/- 0.2 vs 1.0 +/- 0.2 mm, p = <0.001). On HFEE, the average intima plus media thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.78 +/- 0.3 vs 0.34 +/- 0.1 mm, p = 0.005). The average thickness of adventitia was also greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.92 +/- 0.2 vs 0.54 +/- 0.2 mm, p = 0.0005). HR-2DTTE and HFEE measurements of the wall thickness correlated well (r = 0.83 [reader 1], p <0.001; r = 0.61 [reader 2], p <0.01). A third vascular layer, which likely included adventitia, represents a significant portion of the LAD wall thickness imaged by HR-2DTTE and HFEE, and it significantly increases in thickness with the development of atherosclerosis.

Modification of the Ross aortic valve replacement to prevent late autograft dilatation.

OBJECTIVE: Aortic root dilatation with and without aortic regurgitation is seen in up to 20% of patients undergoing a Ross aortic root replacement at late follow-up. We present our early experience with reduction annuloplasty combined with prosthetic Dacron graft replacement of the aorta above the autograft to prevent late dilation after a Ross aortic root replacement. METHODS: Since 2001, 31 of 97 adult and paediatric patients (mean age 28.8+/-14.4 years; range 8-53 years) with bicuspid aortic valve and dilatation of the ascending aorta underwent a modified Ross procedure with reduction annuloplasty combined with prosthetic Dacron graft replacement of the ascending aorta. The diameter of the ascending aorta was measured before and early after surgery and then between 3 months and 8 years' follow-up (mean, 2.5+/-2.2 years). RESULTS: There were no early or late deaths. Reduction annuloplasty combined with ascending aortic graft replacement decreased the diameters of the ascending aorta from 42+/-7.0mm preoperatively to 25+/-2.9 mm early after surgery (p<0.001). During follow-up, there was no significant increase of the aortic diameter compared with that during the postoperative period (27+/-4.3mm; p=0.07). The root diameter increased in only 3 of 31 patients (10%). No patient underwent re-operation. At last follow-up, mild (n=18) or trivial (n=13) aortic regurgitation was observed. CONCLUSION: Ross aortic root replacement combined with reduction annuloplasty and Dacron graft replacement of the ascending aorta demonstrated excellent early- to mid-term results in patients with bicuspid aortic valve and dilatation of the ascending aorta. Continued use and long-term follow-up imaging is necessary to further demonstrate the value of this technical modification.

Midterm results of Ross aortic valve replacement: a single-institution experience.

BACKGROUND: We reviewed our institutional midterm experience to assess autograft and homograft hemodynamics and reoperative frequency after Ross aortic valve replacement. METHODS: Between June 1993 and January 2009, 212 consecutive patients (mean age, 24.8 +/- 15.5 years; range, 1 month to 67 years) underwent Ross aortic valve replacement; 49% were younger than 19 years old. One hundred forty-two additional procedures were required in 101 of the 212 patients (48%) at the time of the Ross aortic valve replacement. One hundred ninety-three patients had isolated aortic valve disease, and 19 pediatric patients had more complex, multilevel left ventricular outflow tract obstruction. RESULTS: There were 2 early (1%) and 2 late deaths (1%), with a mean follow-up of 7.9 +/- 4.2 years (range, 1 month to 15 years). Actuarial survival at 15 years was 98%. To date 28 patients (13%) have required reoperation. At 15 years, freedom from autograft sinus or ascending aortic dilatation was 79%, autograft dysfunction, 91%, autograft reoperation, 89%, and autograft replacement, 96%. Freedom from pulmonary allograft replacement was 96% at 15 years. CONCLUSIONS: The Ross aortic valve replacement can be performed in children and adults with good midterm results. The late complications of autograft regurgitation, sinus or ascending aortic dilatation, can usually be corrected with a valve-sparing root replacement. These complications can often be prevented by (1) aggressive treatment of postoperative systemic hypertension, (2) replacement of a dilated ascending aorta at the initial Ross procedure, or (3) external fixation of the autograft annulus or sinotubular junction. The potential of late autograft insufficiency, ascending aortic and sinus dilatation, or homograft stenosis and insufficiency warrants annual follow-up.

Incidence of and risk factors for pulmonary autograft dilation after Ross aortic valve replacement.

BACKGROUND: The Ross procedure is an alternative to mechanical aortic valve replacement in the young. Early dilation of the pulmonary autograft root exposed to the systemic circulation has been reported. The aim of our study is to define the prevalence, risk factors, and consequences of autograft dilation. All consecutive adult and pediatric patients who underwent Ross procedure at our institution were retrospectively reviewed for autograft dilation. METHODS: Between 1993 and 2005, 170 patients (mean age, 24.9 +/- 15.5 years; range, 1 month to 61 years) underwent Ross aortic valve replacement: 48% were younger than 19 years old. Eighty-seven additional procedures were performed in 58 patients (34%) at the time of the Ross procedure. End points of the study were freedom from autograft dilation (z value more than +2.0), autograft dysfunction, autograft reoperation, and autograft replacement. RESULTS: There were 2 early and 1 late deaths during a mean follow-up of 5.1 +/- 3.0 years (range, 1 month to 12 years). Actuarial survival at 10 years was 98%. Autograft dilation was identified in 31 patients (19%). Regurgitation (>2+) was identified in 12 patients (7%); all 12 had autograft dilation. At 10 years, freedom from autograft dilation was 82%, freedom from autograft dysfunction was 92%, freedom from reoperation on autograft was 92%, and freedom from autograft replacement was 96%. Cox proportional hazard analysis identified preoperative aortic annulus dilation (z value more than +2.0; p = 0.004), younger age (p = 0.05), time of surgery (before 2001; p = 0.002), and male sex (p = 0.01) as predictive of autograft dilation, whereas preoperative ascending aorta diameter (p = 0.01), male sex (p = 0.03), and postoperative systemic hypertension (p = 0.05) were predictive of autograft dysfunction. CONCLUSIONS: Significant autograft dilation is not common after the Ross procedure. Significant autograft dysfunction affects a minority of patients, but it is more prevalent in those with autograft dilation.

Does endogenous testosterone mediate the lower preconditioning threshold in males?

BACKGROUND: Preconditioning is injury-induced protection from subsequent insult. Recent data indicates that males have lower preconditioning thresholds compared to females. Therefore, we hypothesized that testosterone may mediate the lower preconditioning threshold observed in males. MATERIALS AND METHODS: Adult normal and castrated male Sprague-Dawley rats (n = 4-5) were given intraperitoneal (i.p.) injections of 125 or 500 microg/kg Salmonella typhimurium lipopolysaccharide (ETX) or 0.4 ml normal saline (NS). Another i.p. injection of 500 microg/kg ETX (injury dose) was given 24 h later. After 6 h, myocardial function was evaluated via the Langendorff perfusion model. Shams received only NS, while non-preconditioned rats (PC-) received NS followed by the 500 microg/kg ETX injury dose. Preconditioned rats received injections of 125 mug/kg ETX (PC +125) or 500 microg/kg ETX (PC +500), followed by the 500 microg/kg ETX injury dose. RESULTS: Normal PC +125 and PC +500 males were preconditioned and maintained cardiac function similar to shams (P > 0.05). Castrated PC +125 and PC +500 males were also preconditioned and maintained cardiac function similar to castrated shams (P > 0.05). Conversely, both normal and castrated PC-males showed significantly decreased cardiac function compared to shams (P < 0.05). CONCLUSIONS: Endogenous testosterone does not mediate the lower preconditioning threshold in males.

p38 mitogen activated protein kinase mediates both death signaling and functional depression in the heart.

BACKGROUND: Understanding the myocardial inflammatory response to ischemia is an important part of achieving the elusive clinical goal of long-enduring myocardial protection. p38 mitogen-activated protein kinase (MAPK) has been implicated in oxidant stress-induced myocardial tumor necrosis factor production. However, it is unknown whether p38 MAPK mediates the following important events in both myocardial apoptosis and functional depression: mitogen-activated protein kinase-activated protein kinase 2, caspase-1, caspase-3, and caspase-11 activation, and tumor necrosis factor, interleukin-1beta and interleukin-6 production. METHODS: Isolated rat hearts were perfused and subjected to an ischemia-reperfusion insult, with and without preischemic infusion of 20 microM SB203580 (p38 MAPK inhibitor). Myocardial functional measurements were continuously recorded throughout the experiments. Myocardial tissue was then assessed for products of p38 MAPK activation, expression of tumor necrosis factor, interleukin-1beta and interleukin-6, and activation of caspase-1, caspase-3 and caspase-11. RESULTS: Postischemic recovery of left ventricular developed pressure, +dP/dt and -dP/dt was significantly increased by p38 MAPK inhibition (MKI) (left ventricular developed pressure: 48.4 +/- 3.87 MKI versus 32.7 +/- 4.32 mm Hg; +dP/dt: 1392.0 +/- 141.7 MKI versus 896.7 +/- 128.5 mm Hg/s; -dP/dt: -889.9 +/- 97.63 MKI versus -548.9 +/- 71.29 mmHg/s). p38 MAPK inhibition also significantly reduced ischemia-reperfusion-induced elevation of left ventricular end-diastolic pressure (82.76 +/- 4.59 MKI vs 69.95 +/- 3.55 mm Hg). p38 MKI decreased myocardial tumor necrosis factor, interleukin-1beta and interleukin-6 protein levels, and reduced active myocardial caspase-1, caspase-3 and caspase-11. CONCLUSIONS: The p38 MAPK pathway indeed mediates the following important events in myocardial apoptosis and functional depression: mitogen-activated protein kinase-activated protein kinase 2, caspase-1, caspase-3 and caspase-11 activation, and tumor necrosis factor, interleukin-1beta, interleukin-6 production after myocardial ischemia. Single site (p38 MAPK) inhibition of these events may have important therapeutic implications in myocardial protection.

Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies.

Hypoxic pulmonary vasoconstriction is postulated to be an adaptive mechanism to match lung perfusion with ventilation; however, the consequences of the maladaptive effects of pulmonary vasoconstriction represent formidable therapeutic challenges. Understanding the basic mechanisms of hypoxic pulmonary vasoconstriction will enhance the assimilation of translational research into clinical practice. The purposes of this review are to (1) define basic mechanisms of pulmonary vasoconstriction and vasorelaxation; (2) delineate the biphasic contractile response to hypoxia; (3) critically examine data that support the mediator hypothesis versus the ion channel hypothesis; and (4) explore potential mechanistic-based therapies for hypoxic pulmonary vasoconstriction.