Lawrence S. Lee

Recurrence of mitral regurgitation after partial versus complete mitral valve ring annuloplasty for functional mitral regurgitation.

OBJECTIVES Both partial and complete annuloplasty rings are used for mitral valve repair for patients with functional mitral regurgitation (FMR). We sought to determine if recurrence of mitral regurgitation (MR) is affected by the type of ring used. METHODS Five hundred forty-eight patients diagnosed with FMR underwent mitral valve repair with ring annuloplasty between 1998 and 2008 in our institution. Medical records were reviewed retrospectively for clinical and echocardiographic data to determine the presence of recurrent MR (defined as moderate or severe). RESULTS Among 479 patients for whom postoperative echocardiographic data were available, recurrent MR occurred less frequently in the complete versus partial ring group (20 of 209 [10%] vs 56 of 270 [21%] patients; P = .001), despite lower preoperative ejection fractions in the complete ring group (median, 35%; interquartile range, 25%-45% vs median, 40%; interquartile range, 30%-55%; P < .001). Kaplan-Meier analysis demonstrated greater freedom from recurrent MR in the complete ring group (108 vs 103 months; P = .001). Risk-matched propensity analysis of 102 patients per group (area under the curve, 0.824; 95% confidence interval, 0.788-0.861; P < .001) also demonstrated that complete ring recipients had greater freedom from recurrent MR than partial ring recipients by univariate analysis (7 [7%] vs 17 [17%] patients; P = .049), and a trend toward greater freedom by Kaplan-Meier analysis (110 vs 104 months; P = .068). CONCLUSIONS The use of complete mitral annuloplasty rings provides improved freedom from recurrent MR in patients with FMR.

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.

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.

Real-time adjustment of ventricular restraint therapy in heart failure §

OBJECTIVE Current ventricular restraint devices do not allow for either the measurement or adjustment of ventricular restraint level. Periodic adjustment of restraint level post-device implantation may improve therapeutic efficacy. We evaluated the feasibility of an adjustable quantitative ventricular restraint (QVR) technique utilizing a fluid-filled polyurethane epicardial balloon to measure and adjust restraint level post-implantation guided by physiologic parameters. METHODS QVR balloons were implanted in nine ovine with post-infarction dilated heart failure. Restraint level was defined by the maximum restraint pressure applied by the balloon to the epicardium at end-diastole. An access line connected the balloon lumen to a subcutaneous portacath to allow percutaneous access. Restraint level was adjusted while left ventricular (LV) end-diastolic volume (EDV) and cardiac output was assessed with simultaneous transthoracic echocardiography. RESULTS All nine ovine successfully underwent QVR balloon implantation. Post-implantation, restraint level could be measured percutaneously in real-time and dynamically adjusted by instillation and withdrawal of fluid from the balloon lumen. Using simultaneous echocardiography, restraint level could be adjusted based on LV EDV and cardiac output. After QVR therapy for 21 days, LV EDV decreased from 133+/-15 ml to 113+/-17 ml (p<0.05). CONCLUSION QVR permits real-time measurement and physiologic adjustment of ventricular restraint therapy after device implantation.

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.

A Novel, Innovative Ovine Model of Chronic Ischemic Cardiomyopathy Induced by Multiple Coronary Ligations

Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.).