Publications

2012
Shakil O, Mahmood F, Matyal R. Simulation in echocardiography: an ever-expanding frontier. J Cardiothorac Vasc Anesth. 2012;26 (3) :476-85.
Shakil O, Mahmood F. Surgical management of ischemic mitral regurgitation: relearning our lessons. J Cardiothorac Vasc Anesth. 2012;26 (4) :756-7.
Mahmood F, Swaminathan M. Transesophageal echocardiography and noncardiac surgery: how far does the nondiagnostic use go?. J Cardiothorac Vasc Anesth. 2012;26 (2) :356-7.
Shakil O, Josephson ME, Matyal R, Khabbaz KR, Mahmood F. Traumatic right ventricular aneurysm and ventricular tachycardia. Heart Rhythm. 2012;9 (9) :1501-3.
Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, Hacker MR, Rhee JS, Mitchell J, Mahmood F, et al. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature. 2012;485 (7398) :333-8.Abstract
Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.
Malhotra G, Elkassabany NM, Frogel J, Patel AR, Steinberg G, Shaefi S, Mahmood F. CASE 8--2012 intraoperative embolization of renal cell tumor thrombus during radical nephrectomy. J Cardiothorac Vasc Anesth. 2012;26 (6) :1124-30.
Mahmood F, Hess PE, Matyal R, Mackensen BG, Wang A, Qazi A, Panzica PJ, Lerner AB, Maslow A. Echocardiographic anatomy of the mitral valve: a critical appraisal of 2-dimensional imaging protocols with a 3-dimensional perspective. J Cardiothorac Vasc Anesth. 2012;26 (5) :777-84.Abstract
OBJECTIVE: To highlight the limitations of traditional 2-dimensional (2D) echocardiographic mitral valve (MV) examination methodologies, which do not account for patient-specific transesophageal echocardiographic (TEE) probe adjustments made during an actual clinical perioperative TEE examination. DESIGN: Institutional quality-improvement project. SETTING: Tertiary care hospital. PARTICIPANTS: Attending anesthesiologists certified by the National Board of Echocardiography. INTERVENTION: Using the technique of multiplanar reformatting with 3-dimensional (3D) data, ambiguous 2D images of the MV were generated, which resembled standard midesophageal 2D views. Based on the 3D image, the MV scallops visualized in each 2D image were recognized exactly by the position of the scan plane. Twenty-three such 2D MV images were created in a presentation from the 3D datasets. Anesthesia staff members (n = 13) were invited to view the presentation based on the 2D images only and asked to identify the MV scallops. Their responses were scored as correct or incorrect based on the 3D image. METHODS AND MAIN RESULTS: The overall accuracy was 30.4% in identifying the MV scallops. The transcommissural view was identified correctly >90% of the time. The accuracy of the identification of A1, A3, P1, and P3 scallops was <50%. The accuracy of the identification of A2P2 scallops was ≥50%. CONCLUSION: In the absence of information on TEE probe adjustments performed to acquire a specific MV image, it is possible to misidentify the scallops.
Mahmood F, Warraich HJ, Shahul S, Qazi A, Swaminathan M, Mackensen BG, Panzica P, Maslow A. En face view of the mitral valve: definition and acquisition. Anesth Analg. 2012;115 (4) :779-84.Abstract
A 3-dimensional echocardiographic view of the mitral valve, called the "en face" or "surgical view," presents a view of the mitral valve similar to that seen by the surgeon from a left atrial perspective. Although the anatomical landmarks of this view are well defined, no comprehensive echocardiographic definition has been presented. After reviewing the literature, we provide a definition of the left atrial and left ventricular en face views of the mitral valve. Techniques used to acquire this view are also discussed.
Jainandunsing JS, Mahmood F. High transvalvular gradients across a prosthetic valve in the mitral position: not ignoring the bigger picture. J Cardiothorac Vasc Anesth. 2012;26 (5) :968-9.
Shakil O, Matyal R, Khabbaz K, Wang A, Mahmood F. Intracardiac Wegener's granulomatosis. Ann Thorac Surg. 2012;94 (4) :e105.
Matyal R, Chu L, Mahmood F, Robich MP, Wang A, Hess PE, Shahul S, Pinto DS, Khabbaz K, Sellke FW. Neuropeptide Y improves myocardial perfusion and function in a swine model of hypercholesterolemia and chronic myocardial ischemia. J Mol Cell Cardiol. 2012;53 (6) :891-8.Abstract
Pharmacologically induced angiogenesis could be a promising option in clinical situations with diffuse inoperable coronary artery disease e.g. metabolic syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and gene therapies to achieve both perfusion and functional improvement in clinical trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one such natural neurotransmitter that is known to exert a multifaceted role during neo-angiogenesis and can possibly act as the central control. To date, the ability to harness the 'master switch' nature of NPY in a specific experimental model of metabolic syndrome and chronic myocardial ischemia has not been conclusively demonstrated. We hypothesized that infiltration of NPY into an area of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis and improve myocardial perfusion and function. An osmotic pump was inserted three weeks after surgical induction of focal myocardial ischemia. We delivered either NPY or placebo for five weeks, after which the myocardial tissue was harvested for analysis. Assessments of myocardial perfusion and function were performed at each stage of the experiment. Local infiltration of NPY significantly improved collateral vessel formation, blood flow and myocardial function. We believe activation of NPY receptors may be a potential target therapy for patients with diffuse coronary artery disease.
Shahul S, Rhee J, Hacker MR, Gulati G, Mitchell JD, Hess P, Mahmood F, Arany Z, Rana S, Talmor D. Subclinical left ventricular dysfunction in preeclamptic women with preserved left ventricular ejection fraction: a 2D speckle-tracking imaging study. Circ Cardiovasc Imaging. 2012;5 (6) :734-9.Abstract
BACKGROUND: Patients with preeclampsia are at risk for cardiovascular disease. Changes in cardiac function are subtle in preeclampsia and are difficult to quantify with conventional imaging. Strain measurements using speckle-tracking echocardiography have been used to sensitively quantify abnormalities in other disease settings. METHODS AND RESULTS: We evaluated the feasibility and sensitivity of strain imaging using speckle-tracking echocardiography in women with preeclampsia. Forty-seven women were enrolled in this pilot study and 39 were analyzed: 11 with preeclampsia, 17 without a hypertensive disorder, and 11 with nonproteinuric hypertension. Echocardiographic ejection fraction and global peak longitudinal, radial, and circumferential strain were measured. Longitudinal strain was significantly worsened in women with preeclampsia compared with women without a hypertensive disorder (P=0.0001). Similar results were observed for radial strain (P=0.006) and circumferential strain (P=0.03). Women with preeclampsia also had significantly worsened longitudinal (P=0.04), radial (P=0.01), and circumferential (P=0.002) strain compared with women with nonproteinuric hypertension. Women with preeclampsia did not have a significantly different ejection fraction compared with women without a hypertensive disorder (P=0.16) and women with nonproteinuric hypertension (P=0.44). CONCLUSIONS: Myocardial strain imaging using speckle tracking is more sensitive than left ventricular ejection fraction to detect differences in left ventricular systolic function in women with and without preeclampsia.
Shakil O, Jainandunsing JS, Gerstle J, Jones SB, Mahmood F. Can propofol mimic alcohol-related pain in patients with Hodgkin lymphoma?. Anesthesiology. 2012;117 (6) :1399.
Mahmood F, Jainandunsing J, Matyal R. A practical approach to echocardiographic assessment of perioperative diastolic dysfunction. J Cardiothorac Vasc Anesth. 2012;26 (6) :1115-23.Abstract
The Doppler assessment of diastolic dysfunction (DD) is not part of a standard comprehensive intraoperative echocardiographic examination. Although the reasons may be many, the lack of a simplified algorithm for the assessment of DD specific to the perioperative arena, the implications of this diagnosis on clinical care, and the absence of therapeutic options are some of the commonly cited reasons. In this article, the authors address these possible reasons for the lack of routine application of Doppler indices to assess perioperative DD. The authors have chosen to highlight some of the most common conceptual questions, which often have been raised by anesthesiologists, and attempted to suggest answers. Drawing from their experience and data, the authors propose a simplified algorithm for the application of Doppler to assess and diagnose DD with an individualized and a mechanistic approach. The proposed algorithm is from within the premise of the published guidelines and attempts to simplify the perioperative approach. The authors hope this approach will be simple enough for routine application to affect therapy and a tangible change in outcome. The authors suggest that knowledge of left atrial size is valuable as a marker for persistently increased left ventricular end-diastolic pressure and its possible role in risk stratification.
Mahmood F, Warraich HJ, Gorman JH, Gorman RC, Chen T-H, Panzica P, Maslow A, Khabbaz K. Changes in mitral annular geometry after aortic valve replacement: a three-dimensional transesophageal echocardiographic study. J Heart Valve Dis. 2012;21 (6) :696-701.Abstract
BACKGROUND AND AIM OF THE STUDY: Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR). METHODS: A total of 35 patients undergoing elective surgical AVR under cardiopulmonary bypass was enrolled in the study. Intraoperative RT-3D TEE was used prospectively to acquire volumetric echocardiographic datasets immediately before and after AVR. The 3D echocardiographic data were analyzed offline using TomTec Mitral Valve Assessment software to assess changes in specific mitral annular geometric parameters. RESULTS: Datasets were successfully acquired and analyzed for all patients. A significant reduction was noted in the mitral annular area (-16.3%, p < 0.001), circumference (-8.9%, p < 0.001) and the anteroposterior (-6.3%, p = 0.019) and anterolateral-posteromedial (-10.5%, p < 0.001) diameters. A greater reduction was noted in the anterior annulus length compared to the posterior annulus length (10.5% versus 6.2%, p < 0.05) after AVR. No significant change was seen in the non-planarity angle, coaptation depth, and closure line length. During the period of data acquisition before and after AVR, no significant change was noted in the central venous pressure or left ventricular end-diastolic diameter. CONCLUSION: The mitral annulus undergoes significant geometric changes immediately after AVR. Notably, a 16.3% reduction was observed in the mitral annular area. The anterior annulus underwent a greater reduction in length compared to the posterior annulus, which suggested the existence of a mechanical compression by the prosthetic valve.
2011
Maslow A, Singh A, Mahmood F, Poppas A. Intraoperative assessment of mitral valve area after mitral valve repair for regurgitant valves. J Cardiothorac Vasc Anesth. 2011;25 (3) :486-90.
Leissner KB, Srinivasa V, Beutler S, Matyal R, Badr R, Haime M, Mahmood FU. Left atrial dissection and intramural hematoma after aortic valve replacement. J Cardiothorac Vasc Anesth. 2011;25 (2) :309-10.
Matyal R, Bose R, Warraich H, Shahul S, Ratcliff S, Panzica P, Mahmood F. Transthoracic echocardiographic simulator: normal and the abnormal. J Cardiothorac Vasc Anesth. 2011;25 (1) :177-81.
Matyal R, Warraich HJ, Karthik S, Panzica P, Shahul S, Khabbaz KR, Mahmood F. Anterior myocardial infarction with dynamic left ventricular outflow tract obstruction. Ann Thorac Surg. 2011;91 (3) :e39-40.Abstract
We present the case of a 78-year-old woman who presented with acute anterior myocardial infraction. An intraoperative transesophageal echocardiogram revealed an akinetic apex with hyperkinesis of the basal segments causing systolic anterior motion of the mitral valve. The patient was immediately placed on cardiopulmonary bypass. Her postoperative course was uneventful. We present transesophageal and transthoracic echocardiographic videos showing this unique complication and describing the challenge of managing a patient who required opposing therapies.
Matyal R, Mahmood F, Robich M, Glazer H, Khabbaz K, Hess P, Bianchi C, Hagberg R, Hu S-X, Sellke FW. Chronic type II diabetes mellitus leads to changes in neuropeptide Y receptor expression and distribution in human myocardial tissue. Eur J Pharmacol. 2011;665 (1-3) :19-28.Abstract
Neuropeptide Y is one of the most abundant neurotransmitters in the myocardium, and is known to influence cardiovascular remodeling. We hypothesized that diabetic neuropathy could possibly be associated with altered neuropeptide Y and its receptor expression levels in myocardium and plasma. Plasma neuropeptide Y levels in diabetic (n=24, HgbA1c 7.9 ± 1.1%) and non-diabetic (n=27, HgbA1c 5.8 ± 0.5%) patients undergoing cardiac surgery utilizing cardiopulmonary bypass were analyzed. Right atrial tissue of these patients was used to determine the expression of neuropeptide Y, the receptors 1-5, and leptin by immunoblotting, real-time PCR and immunofluorescence. Apoptosis signaling and endostatin and angiostatin were measured to determine the effects of leptin. Plasma neuropeptide Y levels were significantly increased in patients with Type II diabetes mellitus as compared to non-diabetic patients (P=0.026). Atrial tissue neuropeptide Y mRNA levels were lower in diabetic patients (P=0.036). There was a significant up-regulation of myocardial Y(2) and Y(5) receptors (P=0.009, P=0.01 respectively) in the diabetic patients. Leptin, involved with apoptosis and angiogenesis, was down regulated in diabetic patients (P=0.05). The levels of caspase-3, endostatin and angiostatin were significantly elevated in diabetic patients (P=0.003, P=0.008, P=0.01 respectively). Y(1) receptors were more likely to be localized within the nuclei of cardiomyocytes and vascular smooth muscle cells. Neuropeptide expression is altered differentially in the serum and myocardium by diabetes. Altered regulation of this system in diabetics may be in part responsible for the decreased angiogenesis, increased apoptosis, and increased vascular smooth muscle proliferation leading to coronary artery disease and heart failure in this patient population.

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