The 'Pomeroy procedure': a new method to correct post-mitral valve repair systolic anterior motion

Systolic anterior motion (SAM), a recognized complication of mitral valve repair, is often associated with left ventricular outflow gradient and mitral regurgitation. Current surgery to prevent these conditions is to perform sliding annuloplasty to reduce the posterior mitral leaflet (PML) height and to oversize the annuloplasty ring. However, these techniques do not consistently eliminate post-repair SAM, and removal of excess tissue and reduction of anterior mitral leaflet (AML) height may be more effective; this is the 'Pomeroy procedure'. Here, we report a patient in whom all standard procedures to prevent SAM were performed, but the condition still developed. This was corrected on a second pump run, using the Pomeroy procedure.     

Temporary extracorporeal support of the right ventricle

Six patients having severe right ventricular failure after cardiac surgical procedures were treated temporarily with an extracorporeal pump to bypass the right ventricle. The initial operative procedures included coronary artery bypass procedures with and without concomitant valvular and aortic replacement. A Biomedicus centrifugal pump was used as the right ventricular assist device in most cases. The assist period ranged from 3 to 96 hours, and an intra-aortic balloon pump was used in five of the six patients. All patients initially responded to the right ventricular assist device, four were successfully weaned, and one patient is a long-term survivor. The use of a right ventricular assist device is not difficult or complicated and can be lifesaving for those patients having potentially reversible profound right ventricular failure.     

Delayed postoperative cardiac tamponade mimicking severe tricuspid valve stenosis

A patient developed acute, severe hemodynamic deterioration five days after an aortic valve replacement. Cardiac catheterization revealed a markedly elevated right atrial pressure but a normal right ventricular end-diastolic pressure. Angiography revealed an extrinsic mass causing compression of the right atrium and the tricuspid anulus. A large clot overlying the right atrium and ventricle was found at emergency surgery. Postoperative cardiac tamponade may result in an atypical hemodynamic presentation when there is selective compression of one chamber or of a valve anulus.     

Pathological hypertrophy amelioration by PRAS40-mediated inhibition of mTORC1

Mechanistic target of rapamycin complex 1 (mTORC1), necessary for cellular growth, is regulated by intracellular signaling mediating inhibition of mTORC1 activation. Among mTORC1 regulatory binding partners, the role of Proline Rich AKT Substrate of 40 kDa (PRAS40) in controlling mTORC1 activity and cellular growth in response to pathological and physiological stress in the heart has never been addressed. This report shows PRAS40 is regulated by AKT in cardiomyocytes and that AKT-driven phosphorylation relieves the inhibitory function of PRAS40. PRAS40 overexpression in vitro blocks mTORC1 in cardiomyocytes and decreases pathological growth. Cardiomyocyte-specific overexpression in vivo blunts pathological remodeling after pressure overload and preserves cardiac function. Inhibition of mTORC1 by PRAS40 preferentially promotes protective mTORC2 signaling in chronic diseased myocardium. In contrast, strong PRAS40 phosphorylation by AKT allows for physiological hypertrophy both in vitro and in vivo, whereas cardiomyocyte-specific overexpression of a PRAS40 mutant lacking capacity for AKT-phosphorylation inhibits physiological growth in vivo, demonstrating that AKT-mediated PRAS40 phosphorylation is necessary for induction of physiological hypertrophy. Therefore, PRAS40 phosphorylation acts as a molecular switch allowing mTORC1 activation during physiological growth, opening up unique possibilities for therapeutic regulation of the mTORC1 complex to mitigate pathologic myocardial hypertrophy by PRAS40.The mechanistic target of rapamycin (mTOR) kinase is a central cellular hub that couples nutrient sensing and growth factor signaling to cell growth and survival. mTOR signaling is often deregulated in cardiac diseases, and altered growth kinetics, metabolic changes, and increased susceptibility to cell death are characteristics of dysfunctional cardiomyocytes accumulating after cardiac damage. Pharmacological inhibition of mTORC1 with rapamycin improves cardiac function after pressure overload, myocardial infarction, and in genetic hypertrophic cardiomyopathies (1–3). Rapamycin improves cardiac function in patients after kidney transplantation and inhibits the development of cardiac hypertrophy (4), however no established therapeutic regime targets mTOR specifically in cardiomyocytes. As a consequence of the ubiquitous role of mTOR in cell biology, off-target and systemic effects limit clinical use of rapamycin in patients.mTOR exists in two distinct complexes, mTORC1 and mTORC2 (5, 6). Regulatory-associated protein of mammalian target of rapamycin (Raptor) and Proline Rich AKT Substrate of 40 kDa (PRAS40) are specific to mTORC1. Although regulatory mechanisms activating mTORC1 are relatively well understood, those regulating mTORC2 are less characterized. mTORC2 is defined by assembly with rapamycin-insensitive companion of mTOR (Rictor) that has a regulatory role in the insulin signaling cascade and AKT activation (7). PRAS40 interacts with Raptor and inhibits mTORC1 kinase activity (8, 9). PRAS40 contains two proline-enriched stretches at the amino terminus and an AKT consensus phosphorylation site (RXRXXS/T) located at Thr246. Phosphorylated PRAS40 dissociates from mTORC1 in response to growth factors, insulin, glucose, and nutrients, thereby releasing the inhibitory function on mTORC1 (10, 11). Mutation of Thr246 to alanine inhibits AKT-mediated phosphorylation that is important to relieve the inhibitory action of PRAS40 on mTORC1 (9, 12). mTORC1 is an upstream regulator of PRAS40–Ser¹⁸³ phosphorylation, which is important for binding of PRAS40 to Raptor (10, 11). PRAS40 regulates cellular growth and survival in vitro (13), but PRAS40 involvement in the regulation of growth in any tissue remains unexplored. As typical for other well-characterized regulators of cardiac growth and survival [e.g., AKT, proto-oncogene serine/threonine-protein kinase Pim-1 (PIM1), calcineurin], PRAS40 was initially discovered in noncardiac cells, but the relevance of PRAS40 in the myocardium has been overlooked. PRAS40 is widely expressed in various human and mouse tissues, with particularly high expression in the heart (14). In this study we demonstrate the cardioprotective effects of PRAS40-mediated inhibition of mTORC1 using a clinical relevant cardiac gene therapy.     

Improved patient survival after cardiac arrest using a cardiopulmonary support system

A portable cardiopulmonary bypass system that can be rapidly deployed in a nonsurgical setting using nursing staff was used in 38 patients with cardiovascular collapse refractory to ACLS protocol. Percutaneous or cutdown cannulation sites were: femoral vein-femoral artery (n = 18), right internal jugular vein-femoral artery (n = 2), right atrium-ascending aorta (n = 12), or a combination approach (n = 4). Two patients could not be cannulated. Patient diagnoses were pulmonary emboli (n = 3), failed coronary angioplasty (n = 7), myocardial infarction with cardiogenic shock (n = 5), trauma (n = 7), aortic stenosis (n = 2), postcardiotomy deterioration (n = 10), deterioration after cardiac transplantation (n = 2), cardiomyopathy with shock (n = 1), and ruptured ascending aortic dissection (n = 1). Ninety-five percent of patients (36 of 38) were successfully resuscitated to a stable rhythm. Eight diagnostic procedures (coronary angiography, n = 4; pulmonary angiography, n = 3; and aortography, n = 1) were performed while patients were on cardiopulmonary support. Early deaths resulted from massive hemorrhage (n = 8), inability to cannulate (n = 2), and irreversible myocardial injury (n = 10). Sixty-six percent (24 of 36) of patients successfully cannulated underwent conversion to standard cardiopulmonary bypass with attendant operative procedure or placement of ventricular assist device or total artificial heart. Fifty percent (18 of 36) of patients cannulated were successfully weaned from cardiopulmonary support, and 17% (6/36) are long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)