Susan T. Laing

Resistance Exercise in Individuals With and Without Cardiovascular Disease: 2007 Update A Scientific Statement From the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism

Prescribed and supervised resistance training (RT) enhances muscular strength and endurance, functional capacity and independence, and quality of life while reducing disability in persons with and without cardiovascular disease. These benefits have made RT an accepted component of programs for health and fitness. The American Heart Association recommendations describing the rationale for participation in and considerations for prescribing RT were published in 2000. This update provides current information regarding the (1) health benefits of RT, (2) impact of RT on the cardiovascular system structure and function, (3) role of RT in modifying cardiovascular disease risk factors, (4) benefits in selected populations, (5) process of medical evaluation for participation in RT, and (6) prescriptive methods. The purpose of this update is to provide clinicians with recommendations to facilitate the use of this valuable modality.

Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: A randomized controlled trial

CONTEXT Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease (PAD) without intermittent claudication have been established as beneficial. OBJECTIVE To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group. MAIN OUTCOME MEASURES Six-minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow-mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36-Item Short Form Health Survey physical functioning (SF-36 PF) score. RESULTS For the 6-minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m (95% confidence interval [CI], 15.3-56.5 m; P < .001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m (95% CI, -8.42 to 33.3 m; P = .24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow-mediated dilation, those in the treadmill group had a mean improvement of 1.53% (95% CI, 0.35%-2.70%; P = .02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time (3.44 minutes; 95% CI, 2.05-4.84 minutes; P < .001); walking impairment distance score (10.7; 95% CI, 1.56-19.9; P = .02); and SF-36 PF score (7.5; 95% CI, 0.00-15.0; P = .02) than the control group. The resistance training group had greater increases in maximal treadmill walking time (1.90 minutes; 95% CI, 0.49-3.31 minutes; P = .009); walking impairment scores for distance (6.92; 95% CI, 1.07-12.8; P = .02) and stair climbing (10.4; 95% CI, 0.00-20.8; P = .03); and SF-36 PF score (7.5; 95% CI, 0.0-15.0; P = .04) than the control group. CONCLUSIONS Supervised treadmill training improved 6-minute walk performance, treadmill walking performance, brachial artery flow-mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00106327.

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P <.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival.

Thrombolytic efficacy of tissue plasminogen activator-loaded echogenic liposomes in a rabbit thrombus model ☆

INTRODUCTION Ultrasound (US)-enhanced thrombolytic treatment protocols currently in clinical trials for stroke applications involve systemic administration of tissue plasminogen activator (tPA; Alteplase), which carries a risk of adverse bleeding events. The present study aimed to compare the thrombolytic efficacy of a tPA-loaded echogenic liposome (ELIP) formulation with insonification protocols causing rapid fragmentation or acoustically-driven diffusion. MATERIALS AND METHODS Thrombi were induced in the abdominal aortas of male New Zealand white rabbits (2-3kg) using thrombin and a sclerosing agent (sodium ricinoleate) after aortic denudation with a balloon catheter. Thrombolytic and cavitation nucleation agents (200μg of tPA alone, tPA mixed with 50μg of a microbubble contrast agent, or tPA-loaded ELIP) were bolus- injected proximal to the clot through a catheter introduced into the abdominal aorta from the carotid artery. Clots were exposed to transabdominal color Doppler US (6MHz) for 30 minutes at a low mechanical index (MI=0.2) to induce sustained bubble activity (acoustically-driven diffusion), or for 2 minutes at an MI of 0.4 to cause ELIP fragmentation. Degree of recanalization was determined by Doppler flow measurements distal to the clots. RESULTS All treatments showed thrombolysis, but tPA-loaded ELIP was the most efficacious regimen. Both US treatment strategies enhanced thrombolytic activity over control conditions. CONCLUSIONS The thrombolytic efficacy of tPA-loaded ELIP is comparable to other clinically described effective treatment protocols, while offering the advantages of US monitoring and enhanced thrombolysis from a site-specific delivery agent.

Missed opportunities for diagnosis and treatment of diabetes, hypertension, and hypercholesterolemia in a Mexican American population, Cameron County Hispanic Cohort, 2003-2008.

Introduction Diabetes, hypertension, and hypercholesterolemia are common chronic diseases among Hispanics, a group projected to comprise 30% of the US population by 2050. Mexican Americans are the largest ethnically distinct subgroup among Hispanics. We assessed the prevalence of and risk factors for undiagnosed and untreated diabetes, hypertension, and hypercholesterolemia among Mexican Americans in Cameron County, Texas. Methods We analyzed cross-sectional baseline data collected from 2003 to 2008 in the Cameron County Hispanic Cohort, a randomly selected, community-recruited cohort of 2,000 Mexican American adults aged 18 or older, to assess prevalence of diabetes, hypertension, and hypercholesterolemia; to assess the extent to which these diseases had been previously diagnosed based on self-report; and to determine whether participants who self-reported having these diseases were receiving treatment. We also assessed social and economic factors associated with prevalence, diagnosis, and treatment. Results Approximately 70% of participants had 1 or more of the 3 chronic diseases studied. Of these, at least half had had 1 of these 3 diagnosed, and at least half of those who had had a disease diagnosed were not being treated. Having insurance coverage was positively associated with having the 3 diseases diagnosed and treated, as were higher income and education level. Conclusions Although having insurance coverage is associated with receiving treatment, important social and cultural barriers remain. Failure to provide widespread preventive medicine at the primary care level will have costly consequences.

Ultrasound-Enhanced Thrombolytic Effect of Tissue Plasminogen Activator–Loaded Echogenic Liposomes in an In Vivo Rabbit Aorta Thrombus Model—Brief Report

Objective—Ultrasound enhances thrombolysis when combined with a thrombolytic and a contrast agent. This study aimed to evaluate the thrombolytic effect of our tissue plasminogen activator (tPA)–loaded echogenic liposomes (ELIP) in an in vivo clot model, with and without ultrasound treatment. Methods and Results—The femoral arteries of New Zealand White rabbits (n=4 per group) were cannulated. The abdominal aortas were denuded, and thrombi were created using a solution of sodium ricinoleate plus thrombin. Rabbits were then randomly selected to receive tPA-loaded ELIP (200 &mgr;g of tPA/5 mg of lipid) or empty ELIP with or without pulsed (color) Doppler ultrasound (5.7 MHz) for 2 minutes. Thrombus was imaged and echogenicity analyzed before and after ELIP injection. Blood flow velocities were measured at baseline, after clot formation, and serially after treatment up to 15 minutes. tPA-loaded ELIP highlighted thrombus in the abdominal aorta more effectively than empty ELIP (P<0.05). Ultrasound enhanced the thrombolytic effect of tPA-loaded ELIP, resulting in earlier and more complete recanalization rates (P<0.001). Conclusion—This study demonstrates effective highlighting of clots and thrombolytic effect of tPA-loaded ELIP in an in vivo rabbit aorta clot model. Doppler ultrasound treatment enhances this thrombolytic effect, resulting in earlier and more complete recanalization rates.

Cardiovascular therapeutic uses of targeted ultrasound contrast agents

The therapeutic use of ultrasound contrast agents (UCAs) is an emerging methodology with high potential for enhanced directed therapeutic gene, bioactive gas, drug, and stem cell delivery. Ultrasound-targeted microbubble destruction has already demonstrated feasibility for plasmid DNA delivery. Similarly, therapeutic ultrasound for thrombolysis treatment has been taken into the clinical setting, and the addition of UCAs for therapeutic delivery or enhanced effect through cavitation is a natural progression to this investigation. However, as with any new technique, safety needs to be first demonstrated before translation into clinical practice. This review article will focus on the development of UCAs for cardiac and vascular therapeutics as well as the limitations/concerns for the use of therapeutic ultrasound in clinical medicine in order to lay a foundation for investigators planning to enter this exciting field or for those who want to broaden their understanding.

Mitral Valve Repair Using ePTFE Sutures for Ruptured Mitral Chordae Tendineae: A Computational Simulation Study

Mitral valve (MV) repair using expanded polytetrafluoroethylene sutures is an established and preferred interventional method to resolve the complex pathophysiologic problems associated with chordal rupture. We developed a novel computational evaluation protocol to determine the effect of the artificial sutures on restoring MV function following valve repair. A virtual MV was created using three-dimensional echocardiographic data in a patient with ruptured mitral chordae tendineae (RMCT). Virtual repairs were designed by adding artificial sutures between the papillary muscles and the posterior leaflet where the native chordae were ruptured. Dynamic finite element simulations were performed to evaluate pre- and post-repair MV function. Abnormal posterior leaflet prolapse and mitral regurgitation was clearly demonstrated in the MV with ruptured chordae. Following virtual repair to reconstruct ruptured chordae, the severity of the posterior leaflet prolapse decreased and stress concentration was markedly reduced both in the leaflet tissue and the intact native chordae. Complete leaflet coaptation was restored when four or six sutures were utilized. Computational simulations provided quantitative information of functional improvement following MV repair. This novel simulation strategy may provide a powerful tool for evaluation and prediction of interventional treatment for RMCT.

In vivo volumetric intravascular ultrasound visualization of early/inflammatory arterial atheroma using targeted echogenic immunoliposomes.

Objectives:This study aimed to demonstrate three-dimensional (3D) visualization of early/inflammatory arterial atheroma using intravascular ultrasound (IVUS) and targeted echogenic immunoliposomes (ELIP). IVUS can be used as a molecular imaging modality with the use of targeted contrast agents for atheroma detection. Three-dimensional reconstruction of 2-dimensional IVUS images may provide improved atheroma visualization. Materials and Methods:Atheroma were induced in arteries of Yucatan miniswine (n = 5) by endothelial cell denudation followed by a 4-week high cholesterol diet. The contralateral arteries were left intact and served as controls. Anti-intercellular adhesion molecule-1 (ICAM-1) and generic gammaglobulin (IgG) conjugated ELIP were prepared. Arteries were imaged using IVUS before and after ELIP injection. Images were digitized, manually traced, segmented, and placed in tomographic sequence for 3D visualization. Atheroma brightness enhancement was compared and reported as mean gray scale values. Plaque volume was quantified both from IVUS and histologic images. Results:Anti-ICAM-1 ELIP highlighting of the atheroma in all arterial segments was different compared with baseline (P < 0.05). There was no difference in the mean gray scale values with IgG-ELIP. Arterial 3D IVUS images allowed visualization of the entire plaque distribution. The highlighted plaque/atheroma volume with anti-ICAM-1 ELIP was greater than baseline (P < 0.01). Conclusion:This study demonstrates specific highlighting of early/inflammatory atheroma in vivo using anti-ICAM-1 ELIP. Three-dimensional IVUS reconstruction provides good visualization of plaque distribution in the arterial wall. This novel methodology may help to detect and diagnose pathophysiologic development of all stages of atheroma formation in vivo and quantitate plaque volume for serial and long-term atherosclerotic treatment studies.

Evaluation of Mitral Valve Dynamics

Mitral valve (mv) repair is the preferred treatment for patients with mv insufficiency. The unsolved problem in MV repair surgery is predicting the optimal repair for each patient. This is in part due to lack of physiological imaging modalities to provide this information prior to or at the time of valve repair. Moreover, the majority of cases have complex pathophysiological involvement including annular enlargement, chordal lengthening, chordal rupture, calcification, and ultimately lack of proper leaflet coaptation. Current clinical 3-dimensional (3D) transesophageal echocardiography (TEE) can demonstrate volumetric morphology of the MV apparatus. However, biomechanical information is not available from 3D echocardiography. If imaging techniques can be combined with appropriate computational MV evaluation methods, then improved diagnosis and therapeutic approaches to MV repair can be developed. In the present study, we describe a novel comprehensive evaluation protocol to improve diagnosis and treatment of MV pathology by combining 3D TEE and computational simulation techniques (Fig. 1). Virtual MV models were created by utilizing 3D TEE data of patients with normal and pathological MVs followed by computational simulations of MV function. Computational simulations clearly demonstrated deformation and stress distribution of the MV structure across the cardiac cycle at a microsecond scale and corresponded well to 3D TEE data (Figs. 2 and ​and3,3, Online Videos 1, 2, 3, and 4). Here we present 4 case studies (1 normal and 3 different types of pathological MVs). Figure 1 Flow Chart for Virtual MV Modeling and Computational Simulation of MV Function Figure 2 Images of a Normal MV Figure 3 Images of a Pathological MV With Posterior Chordal Rupture Case 1 (Fig. 4): a normal MV demonstrated complete coaptation with no regurgitation when closed. Figure 4 Case 1: A Normal MV With Complete Coaptation; A to D (Peak Systole), E to H (End Diastole) Case 2 (Fig. 5): this MV showed mild regurgitation with relatively small annular dilation. Computational simulation indicated increased leaflet stress values and reduced contact pressure between the leaflets. Figure 5 Case 2: A Degenerative MV With Mild Regurgitation and Small Annular Dilation; A to D (Peak Systole), E to H (End Diastole) Case 3 (Fig. 6): a degenerative MV with large annular dilation demonstrated severe regurgitation by 3D Doppler TEE and the lesion corresponded to regions with no leaflet contact in the computational simulation. Figure 6 Case 3: A Degenerative MV With Severe Regurgitation and Large Annular Dilation; A to D (Peak Systole), E to H (End Diastole) Case 4 (Fig. 7): chordal rupture of this MV caused posterior leaflet prolapse inducing the regurgitant jet. Computational simulation demonstrated an extremely asymmetric and large stress distribution over the leaflets and lack of leaflet coaptation in the regurgitant region. Figure 7 Case 4: A Degenerative MV With Severe Regurgitation due to Ruptured Chordae; A to D (Peak Systole), E to H (End Diastole) Comparative studies of the normal MV (Case 1) and the pathological MV with ruptured chordae (Case 4) clearly demonstrated differences in annular reaction forces and chordal stresses (Fig. 8), and in the degree of leaflet coaptation (Fig. 9, Online Videos 5 and 6). Figure 8 Assessment of Annular Reaction Force and Chordal Stress Distribution; Normal MV (Case 1) Versus MV With Ruptured Chordae (Case 4) Figure 9 Contact Pressure Distribution Between the Leaflets; Normal MV (Case 1) Versus MV With Ruptured Chordae (Case 4) Although MV morphology obtained with 3D TEE image data may demonstrate relatively normal function with no regurgitation, the leaflets may be under extremely high stresses which can result in annular dilation and MV deterioration. Biomechanical information from computational simulation further provides information to help better understand MV pathophysiology. This novel computational strategy has the potential to predict pathophysiological alterations in MV structure, help cardiologists to quantitatively evaluate the extent and severity of MV pathology, and help surgeons to better understand MV dynamics before and following repair to determine more suitable patient-specific repair techniques.