Suyog A. Mokashi

Minimally-invasive valve surgery.

Minimally-invasive approaches have become increasingly important in cardiac valve surgery. Smaller incisions have become commonplace in many major centers. We reviewed the existing literature and present the current state-of-the-art of minimally-invasive valve operations in this paper.

Early results of coronary artery bypass grafting with coronary endarterectomy for severe coronary artery disease.

BackgroundDespite the existence of controversial debates on the efficiency of coronary endarterectomy (CE), it is still used as an adjunct to coronary artery bypass grafting (CABG). This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed.MethodsPatient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA), angina pectoris (CCS) and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis.ResultsBetween August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 ± 9 years. A total of 396 vessels were bypassed (4 ± 0.9 vessels per patient). In 98% left internal thoracic artery (LITA) was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA) (n = 55), on left anterior descending artery (LAD) (n = 52) and circumflex artery (RCX) (n = 7). Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%). Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5). During follow-up (24.5 ± 13.4 months), which is 96% complete (4 patients were lost caused by unknown address) 8 patients died (cardiac failure: 3; stroke: 1; cancer: 1; unknown reasons: 3). NYHA-classification significantly improved after CABG with CE from 2.2 ± 0.9 preoperative to 1.7 ± 0.9 postoperative. CCS also changed from 2.4 ± 1.0 to 1.5 ± 0.8ConclusionEarly results of coronary endarterectomy are acceptable with respect to mortality, NYHA & CCS. This technique offers a valuable surgical option for patients with endstage coronary artery disease in whom complete revascularization otherwise can not be obtained. Careful patient selection will be necessary to assure the long-term benefit of this procedure.

Postoperative Recurrence of Mitral Regurgitation After Annuloplasty for Functional Mitral Regurgitation

BACKGROUND We investigated predictive factors of postoperative recurrence of mitral regurgitation (MR) after mitral valve annuloplasty for functional ischemic MR. METHODS This study was a retrospective review of patients with functional MR who underwent mitral ring annuloplasty at our institution from 1998 to 2008. Records were reviewed for perioperative variables, including echocardiographic measurements. Recurrence was defined as MR grade moderate (3+) or greater on any postoperative echocardiogram. RESULTS Of 548 patients who underwent mitral annuloplasty for functional MR, echocardiogram reports were available for review for 250. These patients comprised the study cohort. There were 154 patients with concomitant coronary artery bypass grafting. The left ventricular (LV) end-diastolic (LVED) index was calculated by dividing the LVED dimension by body surface area (BSA). A high LVED index (>3.5 cm/m2) was predictive of MR recurrence (p=0.047): the recurrence rate was 20.3% (13 of 64) in high-index patients and 10.2% (19 of 186) in low-index (<3.5 cm/m2) patients. Median recurrence-free survival was 35 months (range, 19 to 59 months) in high-LVED-index patients and 46.5 months (range, 22 to 75 months) in low-LVED-index patients (p=0.048). Preoperative MR severity and LV ejection fraction were not predictive of MR recurrence. CONCLUSIONS Careful analysis of the preoperative echocardiogram using a novel, easily calculated variable, the LVED index, may help identify patients who are at greater risk for MR recurrence and reduced survival. Such information could prompt consideration of alternative or additional interventions in these patients.

AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart

Adenosine monophosphate – activated kinase (AMPK) plays a key role in the coordination of the heart’s anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating β - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ – subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.

Functional Mitral Regurgitation

Functional mitral regurgitation (MR) is a common clinical entity which will likely increase in the future due to predicted demographic changes. It is also associated with poor long-term survival. The anatomic structure of the mitral valve apparatus is complex and consists of several components, each of which can be affected by a variety of diseases resulting in MR. In primary MR, the valvular incompetence is caused by compromised or structurally disrupted components of the valve apparatus; the valve in functional MR is structurally normal, with the regurgitation resulting from failure of coaptation of the mitral valve leaflets without coexisting structural changes of the valve itself. Therefore, we defined functional MR as a systolic retrograde flow from the left ventricle into the left atrium due to reduction and/or elimination of the normal systolic coaptation of the mitral valve leaflets. A slow progression of the symptoms is typical for this valve disease and often ends in irreversible left ventricular dysfunction. The pathophysiology and treatment of functional MR are quite complex. This article reviews and summarizes the existing literature, with a focus on the pathophysiology and current treatment of functional MR.

Ventricular assist device in patients with prosthetic heart valves.

Ventricular assist device (VAD) support inpatients with a prosthetic heart valve had previously been considered a relative contraindication due to an increased risk of thromboembolic complications. We report our clinical experience of VAD implantation in patients with prosthetic heart valves, including both mechanical and bioprosthetic valves. The clinical records of 133 consecutive patients who underwent VAD implantation at a single institution from January 2002 through June 2009 were retrospectively reviewed. Six of these patients had a prosthetic valve in place at the time of device implantation. Patient demographics,operative characteristics, and postoperative complications were reviewed.Of the six patients,four were male.The mean age was 57.8 years (range 35–66 years). The various prosthetic cardiac valves included a mechanical aortic valve (n = 2), a bioprosthetic aortic valve (n = 3), and a mechanical mitral valve (n = 1).The indications for VAD support included bridge to transplantation (n = 2), bridge to recovery (n = 1), and postcardiotomy ventricular failure(n = 3). Three patients underwent left ventricular assist device placement and three received a right ventricular assist device. Postoperatively, standard anticoagulation management began with a heparin infusion (if possible)followed by oral anticoagulation.The 30-day mortality was50% (3/6). The mean duration of support among survivors was 194.3 days (range 7–369 days) compared with 16.0 days(range 4–29 days) for nonsurvivors. Of the three survivors,two were successfully bridged to heart transplantation and one recovered native ventricular function.Among the three nonsurvivors,acute renal failure developed in each case, and two developed heparin-induced thrombocytopenia. This study suggests that VAD placement in patients with a prosthethic heart valve, either mechanical or bioprosthetic,appears to be a reasonable option.

Large Animal Models of Chronic Heart Failure (CHF)

Epidemiologic studies have revealed an annual incidence of congestive heart failure in the United States and Europe of 0.3% to 1.0% [1]. In cardiovascular research, large animal models are necessary to examine the pathophysiology and surgical treatments of heart failure. Although a large variety of animal models to study acute heart failure exist, valuable models on the effects of ventricular assist devices in chronic heart failure (CHF) are scarce. These models have been created depending on the specific scientific question, as well as on factors such as accessibility, reproducibility, ethical, and financial considerations. To study pathophysiologic processes, such as the development of heart failure or how mechanical unloading by ventricular assist devices can induce reverse remodeling, animal models should closely mimic the human clinical findings. We reviewed the existing literature and summarized various large animal models of CHF with particular focus on the advantages and disadvantages of each model.

Ventricular restraint therapy for heart failure: The right ventricle is different from the left ventricle

OBJECTIVE Effects of ventricular restraint on the left ventricle are well documented, but effects on the right ventricle are not. We hypothesized that restraint affects the right and left ventricles differently. METHODS We studied acute effects of restraint on left and right ventricular mechanics in healthy sheep (n = 14) with our previously described technique of adjustable and measurable restraint. Transmural pressure, myocardial oxygen consumption indices, diastolic compliance, and end-systolic elastance were assessed at 4 restraint levels for both ventricles. We then studied long-term effects of restraint for 4 months in an ovine model of ischemic dilated cardiomyopathy (n = 6). Heart failure was induced by coronary artery ligation, and polypropylene mesh was wrapped around the heart to simulate clinical restraint therapy. All subjects were followed up with serial cardiac magnetic resonance imaging to assess left and right ventricular volumes and function. RESULTS Restraint decreased left ventricular transmural pressure (P < .03) and myocardial oxygen consumption indices (P < .05) but not left ventricular diastolic compliance (P = .52). Restraint had no effect on right ventricular transmural pressure (P = .82) or myocardial oxygen consumption indices (P = .72) but reduced right ventricular diastolic compliance (P < .01). In long-term studies, restraint led to reverse left ventricular remodeling with decreased left ventricular end-diastolic volume (P < .006) but did not affect right ventricular end-diastolic volume (P = .82). CONCLUSIONS Ventricular restraint affects the left and right ventricles differently. Benefits of restraint for right ventricular function are unclear. The left ventricle can tolerate more restraint than the right ventricle. With current devices, the right ventricle may limit overall therapeutic efficacy.

Preventing cardiac remodeling: The combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia

OBJECTIVE Cellular and mechanical treatment to prevent heart failure each holds therapeutic promise but together have not been reported yet. The goal of the present study was to determine whether combining a cardiac support device with cell-based therapy could prevent adverse left ventricular remodeling, more than either therapy alone. METHODS The present study was completed in 2 parts. In the first part, mesenchymal stem cells were isolated from rodent femurs and seeded on a collagen-based scaffold. In the second part, myocardial infarction was induced in 60 rats. The 24 survivors were randomly assigned to 1 of 4 groups: control, stem cell therapy, cardiac support device, and a combination of stem cell therapy and cardiac support device. Left ventricular function was measured with biweekly echocardiography, followed by end-of-life histopathologic analysis at 6 weeks. RESULTS After myocardial infarction and treatment intervention, the ejection fraction remained preserved (74.9-80.2%) in the combination group at an early point (2 weeks) compared with the control group (66.2-82.8%). By 6 weeks, the combination therapy group had a significantly greater fractional area of change compared with the control group (69.2% ± 6.7% and 49.5% ± 6.1% respectively, P = .03). Also, at 6 weeks, the left ventricular wall thickness was greater in the combination group than in the stem cell therapy alone group (1.79 ± 0.11 and 1.33 ± 0.13, respectively, P = .02). CONCLUSIONS Combining a cardiac support device with stem cell therapy preserves left ventricular function after myocardial infarction, more than either therapy alone. Furthermore, stem cell delivery using a cardiac support device is a novel delivery approach for cell-based therapies.

Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy.

OBJECTIVE The effects of ventricular restraint level on left ventricular reverse remodeling are not known. We hypothesized that restraint level affects the degree of reverse remodeling and that restraint applied in an adjustable manner is superior to standard, nonadjustable restraint. METHODS This study was performed in 2 parts using a model of chronic heart failure in the sheep. In part I, restraint was applied at control (0 mm Hg, n = 3), low (1.5 mm Hg, n = 3), and high (3.0 mm Hg, n = 3) levels with an adjustable and measurable ventricular restraint (AMVR) device. Restraint level was not altered throughout the 2-month treatment period. Serial restraint level measurements and transthoracic echocardiography were performed. In part II, restraint was applied with the AMVR device set at 3.0 mm Hg (n = 6) and adjusted periodically to maintain that level. This was compared with restraint applied in a standard, nonadjustable manner using a mesh wrap (n = 6). All subjects were followed up for 2 months with serial magnetic resonance imaging. RESULTS In part I, there was greater and earlier reverse remodeling in the high restraint group. In both groups, the rate of reverse remodeling peaked and then declined as the measured restraint level decreased with progression of reverse remodeling. In part II, adjustable restraint resulted in greater reverse remodeling than standard restraint. Left ventricular end diastolic volume decreased by 12.7% (P = .005) with adjustable restraint and by 5.7% (P = .032) with standard restraint. Left ventricular ejection fraction increased by 18.9% (P = .014) and 14.4% (P < .001) with adjustable and standard restraint, respectively. CONCLUSIONS Restraint level affects the rate and degree of reverse remodeling and is an important determinant of therapy efficacy. Adjustable restraint is more effective than nonadjustable restraint in promoting reverse remodeling.