Deactivation of LVAD support for myocardial recovery-surgical perspectives.

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation.

A Targeted Management Approach to Cardiogenic Shock.

Cardiogenic shock is a clinical syndrome characterized by low cardiac output and sustained tissue hypoperfusion resulting in end-organ dysfunction and death. In-hospital mortality rates range from 50% to 60%. Urgent diagnosis, timely transfer to a tertiary or quaternary medical facility with critical care management capabilities and multidisciplinary shock teams is a must to increase survival. Aggressive, hemodynamically guided medical management with careful monitoring of clinical and hemodynamic parameters with timely use of appropriate mechanical circulatory support devices is often necessary. As treatment options evolve, prospective randomized controlled trials are needed to define best practices that define superior clinical outcomes.

Fulminant Infectious Aortitis With Ascending Aortic Rupture.

Infectious aortitis is associated with a high rate of acute aortic adverse events. However, the nonspecificity of symptoms and low sensitivity of blood cultures may delay early recognition of this condition. A 77-year-old man was incidentally found to have aortitis. His disease took a fulminant course and was complicated by dissection and rupture only 4 days after the diagnosis. Serial computed tomographic angiography provided valuable information about the development of aortitis into dissection and rupture. Postdissection histologic analysis revealed gram-positive cocci in the aortic wall.

Heart Procurement from a Donor on Venovenous ECMO Support.

We report the case of a 37-year-old woman with acute respiratory distress syndrome and became a candidate for organ donation after anoxic brain injury and was on a venovenous extracorporeal membrane oxygenation (VV-ECMO) support. On preoperative evaluation and gross examination, the donor's heart was acceptable for heart transplantation to a 62-year-old female patient with a history of nonischemic cardiomyopathy with a HeartMate II mechanical assist device. Orthotopic heart transplantation was successfully performed in the recipient. We report a case that suggests that the procurement of a heart from a donor on ECMO support can potentially expand the donor heart pool in carefully selected patients.

Effect of pulmonary vascular resistance before left ventricular assist device implantation on short- and long-term post-transplant survival.

OBJECTIVES: Pulmonary hypertension is often considered a contraindication to orthotopic heart transplantation. Left ventricular assist device support may improve pulmonary hypertension by unloading the left ventricle, making patients eligible for transplantation. We sought to investigate the effect of continuous-flow left ventricular assist device support on pulmonary hypertension and compare post-transplantation outcomes in patients with preexisting pulmonary hypertension. METHODS: Between March 2004 and December 2013, 256 potential orthotopic heart transplantation candidates underwent continuous-flow left ventricular assist device implantation at Columbia University. Preimplantation right heart catheterization data were available for 227 patients. Patients were divided into 2 groups on the basis of preimplantation pulmonary vascular resistance: low (<5 Wood units) (n = 182) and high (≥5 Wood units) (n = 45). Postimplantation and post-transplantation outcomes were compared between the groups. RESULTS: Pulmonary vascular resistance in the high resistance group decreased significantly during left ventricular assist device support (P < .001). Post-transplantation in-hospital mortality was significantly higher in patients with high vascular resistance (P < .05). However, 3-year survival after transplantation was similar between groups (85.0% and 79.0% for low and high vascular resistance, respectively; P = .45). CONCLUSIONS: Continuous-flow left ventricular assist device therapy reduced pulmonary vascular resistance. Subsequent orthotopic heart transplantation in patients with significantly elevated pulmonary vascular resistance resulted in higher in-hospital mortality but similar 3-year survival.

Periscope modification of right ventricle-to-pulmonary artery shunt in Norwood operation.

Given the purported hemodynamic advantages of the right ventricle (RV) to pulmonary artery (PA) conduit, many surgeons have adopted it as their preferred source of pulmonary blood flow during stage I palliation for hypoplastic left heart syndrome. Potential disadvantages of the RV-PA shunt include ventricular dysfunction, pseudoaneurysm formation, arrhythmia, and conduit obstruction, which can lead to a higher rate of unplanned reinterventions. The "dunk" technique was described to reduce the RV incision and proximal conduit obstruction; however, insertion of the ringed graft from the epicardium can be cumbersome and risk RV injury. We introduce a simplified, alternative method of placing the conduit, which we call the periscope technique, whereby the graft is withdrawn from within the RV cavity.

Type A aortic dissection: a rare complication of central venous catheter placement.

Aortic injury during central venous catheter (CVC) insertion is an extremely rare complication. We report successful repair of an iatrogenic type A aortic dissection caused during mediport catheter insertion and discuss the prevention and management of aortic injury during CVC placement.

Uterine cells are recruited to the infarcted heart and improve cardiac outcomes in female rats.

We evaluated the hypothesis that uterine cells home to the heart after injury and improve cardiac outcomes. Premenopausal women have fewer cardiovascular complications than age-matched men, but the mechanisms responsible for this protection have not been conclusively identified. Hysterectomy was performed in young female rats (leaving the ovaries intact), and 7 days later the left coronary artery was ligated to produce a myocardial infarction (MI). Cardiac function at 28 days post-MI was measured using echocardiography. Fractional shortening was best in non-hysterectomized (non-Hx) females and lower in both Hx females and males. Uteri were then removed from GFP rats and heterotopically transplanted into non-GFP recipients to investigate homing of uterine cells to the infarcted myocardium. Seven days later, the uterine transplant recipients underwent coronary ligation. GFP(+) cells were found in the recipient hearts 7 days after MI and persisted for 6 months. Confocal analysis showed that homed uterine cells were located around blood vessels, suggesting their involvement in neovascularization. We then evaluated uterine cell transplantation by intravenously injecting GFP(+) uterine cells into Hx females immediately after MI. These GFP(+) cells were found to home to the injured myocardium, stimulate angiogenesis, improve cardiac function, and increase survival. This study demonstrates that uterine cells can home to the injured myocardium, enhance tissue repair, and prevent cardiac dysfunction. Uterine cells may play a role in the prevention of cardiovascular complications in females.

Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis.

OBJECTIVE: Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a "bridge to recovery." However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation. METHODS: Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation. RESULTS: Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and ß-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL. CONCLUSIONS: Mechanical unloading preserved myocardial contractility and ß-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.

Carvedilol may alleviate late cardiac remodelling following surgical ventricular restoration.

OBJECTIVE: Surgical ventricular restoration (SVR) can be effective to treat ischaemic cardiomyopathy or left ventricular (LV) aneurysm. However, the initial improvement in LV function does not always last long because of LV remodelling. Beta-blockers prevent LV remodelling of failing hearts; however, their effects following SVR have not been elucidated. Thus, we sought to investigate the effects of a potent beta-blocker, carvedilol, on LV remodelling and function following SVR in rats with myocardial infarction. METHODS: Rats, which developed LV aneurysm 4 weeks after coronary artery ligation, underwent SVR. They were orally administered a vehicle (vehicle group), and low or high dose of carvedilol (20 or 50 mg kg(-1)day(-1) for C20 or C50 group) for 4 weeks following SVR (n=7 in each group). RESULTS: Four weeks following SVR, late cardiac remodelling was alleviated only in the C50 group (LV end-diastolic area: 65+/-4 mm(2) vs 74+/-11 mm(2) and 76+/-11 mm(2) for C50, C20 and vehicle groups; p=0.039 and p=0.013, respectively). There was no difference in LV systolic function (end-systolic elastance) among the three groups; however, LV diastolic functions (LV end-diastolic pressure and the time constant of isovolumic relaxation) were significantly better in the C20 and C50 groups. Histologically, the percentage of myocardial fibrosis in the C50 group (4.1+/-0.2%) was lower than those in the C20 (6.7+/-0.4%, p<0.0001) and vehicle (7.5+/-0.6%, p<0.0001) groups. The mRNA expression of transforming growth factor-beta1 and brain natriuretic peptide in the C50 group were lower than those in the C20 and the vehicle groups. CONCLUSIONS: High-dose carvedilol alleviated LV remodelling and diastolic dysfunction following SVR accompanying with reduction in myocardial fibrosis. Blockade of beta-adrenergic receptor may be a promising adjuvant therapy in patients following SVR.

Chronic partial unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in failing rat hearts.

OBJECTIVES: Mechanical unloading with a left ventricular assist device promotes "reverse remodeling," including restoration of beta-adrenergic receptor signaling and function. We compared the effects of partial unloading and complete unloading on beta-adrenergic responsiveness and gene expressions in failing rat hearts by use of heterotopic heart-lung or heart transplantation models. METHODS: Four weeks after ligation of the left anterior descending artery in Lewis rats, rats with heart failure were divided into 3 groups: infarcted hearts and lungs transplanted into the recipient rats (heart failure-partial unloading, n = 8); infarcted hearts transplanted into the recipient rats (heart failure-complete unloading, n = 7); infarcted (heart failure, n = 8) hearts without transplantation. Normal rats (n = 7) were used as controls. Papillary muscle function and gene expressions were studied at 2 or 4 weeks after transplantation. RESULTS: In 2-week models, baseline developed tension of papillary muscles significantly increased in heart failure-partial unloading and heart failure-complete unloading compared with heart failure (0.15 +/- 0.07 and 0.12 +/- 0.05 g/mm(2) vs 0.02 +/- 0.01 g/mm(2), P < .05). However, in 4-week models, they decreased to 0.11 +/- 0.03 and 0.10 +/- 0.03 g/mm(2). In 4-week but not in 2-week models, the increase from baseline in baseline developed tension produced by beta-adrenergic stimulation (isoproterenol, 10(-8) and 10(-7) mol/L) was significantly increased in heart failure-partial unloading compared with heart failure-complete unloading and heart failure (P < .05). The mRNA expressions of brain natriuretic peptide and beta(1)- and beta(2)-adrenergic receptors were normalized in both 2- and 4-week models of heart failure-partial unloading. CONCLUSIONS: Chronic partial unloading but not complete unloading improved beta-adrenergic responsiveness and normalized brain natriuretic peptide and beta(1)- and beta(2)-adrenergic receptor mRNA expressions in the failing rat hearts.

Spironolactone alleviates late cardiac remodeling after left ventricular restoration surgery.

OBJECTIVE: Although left ventricular restoration is effective for treating ischemic cardiomyopathy caused by left ventricular remodeling and redilation, the initial improvement in left ventricular function is not always sustained. We have reported that the inhibition of the renin-angiotensin-aldosterone system by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is effective in preventing late remodeling after left ventricular restoration. However, the effects of spironolactone--an aldosterone blocker--after left ventricular restoration have not been elucidated. METHODS: Myocardial infarction was induced by ligating the left anterior descending artery. The rats developed left ventricular aneurysms and underwent left ventricular restoration by the plication of the left ventricular aneurysm 4 weeks after the ligation. Thereafter, the rats were randomized into a left ventricular restoration (vehicle) group and left ventricular restoration with spironolactone (100 mg/kg/d, by mouth) group. RESULTS: Echocardiography revealed that in the left ventricular restoration with spironolactone group, late cardiac redilation was significantly attenuated (left ventricular end-diastolic area: 0.51 +/- 0.03 cm(2) vs 0.63 +/- 0.03 cm(2), P < .05) and late left ventricular function was preserved (fractional area change: 48.8% +/- 3.0% vs 35.8% +/- 2.4%, P < .01). Hemodynamically, rats in the left ventricular restoration with spironolactone group exhibited improved systolic function (maximal end-systolic pressure-volume relationship: 0.38 +/- 0.03 mm Hg/microL vs 0.11 +/- 0.04 mm Hg/microL, P < .01) and diastolic function (tau: 18.5 +/- 1.5 sec vs 23.1 +/- 1.4 sec, P < .05) than those in the LVR group. Histologically, interstitial fibrosis in the remote area was significantly reduced (5.6% +/- 1.3% vs 12% +/- 1.0%, P < .01), and fibrosis around the pledgets (near area) was also attenuated in the left ventricular restoration with spironolactone group. The myocardial messenger ribonucleic acid expressions of transforming growth factor-beta1 and brain natriuretic peptide measured using the real-time polymerase chain reaction were lower in the left ventricular restoration with spironolactone group (transforming growth factor-beta1: 0.13 +/- 0.02 vs 0.28 +/- 0.02, P < .01; brain natriuretic peptide: 0.99 +/- 0.14 vs 1.54 +/- 0.18, P < .05). The systemic blood pressure and heart rate did not differ between the 2 groups. CONCLUSION: Spironolactone reduced the gene expression of transforming growth factor-beta1 and brain natriuretic peptide and alleviated not only cardiac redilation but also the deterioration of left ventricular function late after left ventricular restoration without inducing hypotension, a major side effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker. Spironolactone is a promising therapeutic option for alleviating remodeling after left ventricular restoration.

Gastroepiploic artery grafting does not improve the late outcome in patients with bilateral internal thoracic artery grafting.

BACKGROUND: Bilateral internal thoracic artery grafting in coronary artery bypass surgery has a better long-term outcome than single internal thoracic artery grafting. However, the efficacy of gastroepiploic artery (GEA) grafting in addition to bilateral internal thoracic artery grafting is still not well-established. METHODS: From 1989 to 1999, 311 patients underwent coronary artery bypass grafting using in situ bilateral internal thoracic arteries anastomosed to the left coronary arteries and either an in situ GEA or a saphenous vein graft (SVG) anastomosed to the right coronary artery. Ninety-nine patients using the in situ GEA (GEA group) were compared with 212 patients using the SVG (SVG group) anastomsed to the right coronary artery. Young patients and patients with hyperlipidemia were more prevalent in the GEA group. RESULTS: The seven-year survival rate in the GEA group and the SVG group were 94.7% and 87.2%, respectively (p = 0.068). In a multivariate analysis, the age, renal failure, and a low ejection fraction (<0.40) were all significant predictors of survival. The GEA was not a significant predictor. The seven-year freedom rates from cardiac events were similar in both groups (GEA group, 76.5%; SVG group, 78.6%; p = 0.455). The seven-year freedom rates from recurrent angina were also similar between the groups (GEA group, 85.3%; SVG group, 88.8%; p = 0.700). CONCLUSIONS: In comparison with SVG grafting, GEA grafting to the right coronary artery did not significantly improve the late outcomes in patients with bilateral internal thoracic artery grafting.