Baseline Quality-of-Life of Caregivers of Patients With Heart Failure Prior to Advanced Therapies: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT) Study.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ2 tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R2 = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

Mycotic pseudoaneurysm of the ascending aorta after heart transplantation: case report.

Mycotic pseudoaneurysm of the ascending aorta is a rare but potentially life-threatening complication after orthotopic heart transplantation. We present a case of a 53-year-old man who developed a mycotic pseudoaneurysm of the ascending aorta after orthotopic heart transplantation. The pseudoaneurysm was surgically resected and the ascending aorta was replaced with allograft. The Gram stain and multiple cultures of the pseudoaneurysm wall revealed that the causative microorganism was coagulase-negative Staphylococcus. To the best of our knowledge, this is the first case report that describes mycotic pseudoaneurysm owing to coagulase-negative Staphylococcus infection after heart transplantation. Although S aureus and Pseudomonas aeruginosa are common pathogens in previously published literatures describing mycotic pseudoaneurysms in heart transplant recipients, coagulase-negative Staphylococcus is aslo an important and virulent pathogen that can cause mycotic aortic pseudoaneurysm in immunosuppressed patients. Once diagnosed, aggressive surgical treatment with prudent operative strategy, appropriate postoperative antibiotic therapy and close follow-up by radiographic study are mandatory in managing patients with this potentially fatal condition.

Current status of cardiac surgery in the abciximab-treated patient.

BACKGROUND: Early surgical experience with abciximab and other glycoprotein (GP) IIb/IIIa receptor antagonists suggested a tendency toward excessive bleeding in patients treated with these agents. With increased use of GP IIb/IIIa inhibitors, cardiac surgeons have become aware of their hazards, as well as potential benefits, during and after cardiac surgery. Although published experience with the GP IIb/IIIa inhibitor abciximab is limited in scope, it suggests management guidelines for urgent coronary artery bypass grafting in abciximab-treated patients. As more urgent and elective surgical data are presented, a clearer picture of true bleeding risk will evolve. METHODS: Two large retrospective studies examining reexploration for postoperative bleeding have identified risk factors, including advanced age, preoperative renal dysfunction, and operation/reoperation other than coronary artery bypass grafting. Other risk factors for transfusion requirement and increased morbidity and mortality are emergent operation, postoperative coagulopathy, and prolonged bypass time. RESULTS: To minimize real and perceived bleeding effects, some authors have suggested delaying operation until platelet function has normalized, employing platelet transfusion in patients in whom delay is not possible, and exacting heparin management during cardiopulmonary bypass. Later reports have not noted increased bleeding when incorporating these modifications plus early platelet transfusion, if required. Further experience with abciximab removal and reversal may also ultimately reduce or eliminate excess transfusion requirements. CONCLUSIONS: Surgeons should work closely with perfusionists and anesthesiologists on issues of heparinization in the abciximab-treated patient. The apparent paradox of preserved platelet numbers and depressed platelet function with abciximab use has led to speculation about a role for this agent and other shorter-acting GP IIb/IIIa inhibitors for "platelet anesthesia" during cardiopulmonary bypass. With careful surgical care, GP IIb/IIIa receptor antagonists can maintain and improve beneficial outcomes.

Calcitonin gene-related peptide enhances the recovery of contractile function in stunned myocardium.

INTRODUCTION: Calcitonin gene-related peptide, a potent vasodilating inotropic agent, increases coronary artery perfusion when administered exogenously and reduces ischemic injury in nonmyocardial tissue. However, it is unclear whether this agent improves recovery of myocardial performance after reversible myocardial ischemia. METHODS: Nine dogs underwent complete occlusion of the left anterior descending coronary artery for 15 minutes and were monitored during 24 hours of reperfusion. Calcitonin gene-related peptide (0.07 microgram. kg(-1). min(-1)), nitroglycerin (65 microgram. kg(-1). min(-1)), or saline solution placebo was infused intravenously during initial reperfusion. Ischemia/reperfusion was repeated in concurrent 24-hour periods until all animals received infusions in random order. Micromanometry and sonomicrometry determined left ventricular pressure and myocardial segment length. Myocardial performance, based on the linear relationship between stroke work and end-diastolic segment length, was estimated with the preload recruitable work area. Results were analyzed as percent control and compared statistically with the use of repeated measures analysis of variance. RESULTS: Recovery of myocardial performance was augmented during reperfusion with calcitonin gene-related peptide infusion relative to placebo

Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart : prospects for molecular ventricular assistance.

BACKGROUND: Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of beta(2)-adrenergic receptors (beta(2)ARs) has been shown to enhance contractility in transgenic mice and reverse signaling abnormalities found in failing cardiomyocytes in culture. In this study, we sought to determine the feasibility and in vivo consequences of delivering an adenovirus containing the human beta(2)AR cDNA to ventricular myocardium via catheter-mediated subselective intracoronary delivery. METHODS AND RESULTS: Rabbits underwent percutaneous subselective catheterization of either the left or right coronary artery and infusion of adenoviral vectors containing either a marker transgene (Adeno-betaGal) or the beta(2)AR (Adeno-beta(2)AR). Ventricular function was assessed before catheterization and 3 to 6 days after gene delivery. Both left circumflex- and right coronary artery-mediated delivery of Adeno-beta(2)AR resulted in approximately 10-fold overexpression in a chamber-specific manner. Delivery of Adeno-betaGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of beta(2)ARs in the LV improved global LV contractility, as measured by dP/dt(max), at baseline and in response to isoproterenol at both 3 and 6 days after gene delivery. CONCLUSIONS: Percutaneous adenovirus-mediated intracoronary delivery of a potentially therapeutic transgene is feasible, and acute global LV function can be enhanced by LV-specific overexpression of the beta(2)AR. Thus, genetic modulation to enhance the function of the heart may represent a novel therapeutic strategy for congestive heart failure and can be viewed as molecular ventricular assistance.

Means for load variation during echocardiographic assessment of the Frank-Starling relationship.

Because minimally invasive methods of preload variation are not validated for load-insensitive indexes of cardiac performance, intravenous nitroglycerin (NTG), phenylephrine, and saline solution (VOL) boluses were used in blocked and intact autonomic states to alter load and were compared with vena caval occlusion in the assessment of preload recruitable stroke work relationships between stroke work and left ventricular end-diastolic volume in dogs. In both autonomic states NTG and VOL produced comparable linear relationships. NTG and saline solution were combined with noninvasive measurements of left ventricular pressure and volume to construct echocardiographic relationships between stroke work and left ventricular end-diastolic cross-sectional area; NTG produced linear relationships similar to vena caval occlusion. Therefore NTG and VOL reliably alter load in constructing preload recruitable stroke work relationships, and NTG may be used with noninvasive measurements to provide load-insensitive estimates of cardiac function in a minimally invasive manner.

Ventricular and myocardial efficiencies during acute aortic regurgitation in conscious dogs.

BACKGROUND: Alterations in cardiac efficiency may signal pathologic stresses and energetic adaptation during aortic regurgitation (AR). METHODS AND RESULTS: LV systolic function, left coronary blood flow, and AVO2 difference were measured in conscious dogs to assess LV and contractile efficiencies at baseline, 1 day (n=10), 1 week (n=10), and 3 weeks (n=8) of AR. LV systolic function was assessed by the preload recruitable stroke work relationship. Total LV Efficiency (TEFF=SWxHeart Rate/MVO2) and contractile efficiency (CEFF=1/the slope of the MVO2 -pressure-volume area relationship) and steady-state potential energy (PVA-SWxHR), mechanical coupling efficiency (MCE=SWxHR/PVA) were calculated. LV systolic function decreased by 17% at 1 day (P<.05) and by 24% at 3 weeks (P<.05). CEFF decreased from 58+/-8% to 38+/-10% (P<.05) at 1 day, normalized at 1 week, and decreased to 28+/-14% at 3 weeks (P<.05). TEFF was not altered at 1 day and 1 week but decreased by 3 weeks (P<.05). MCE trended downward from baseline of 47+/-5%, reaching significance at 3 weeks (34+/-6%, P<.05). CONCLUSIONS: CEFF decreases acutely, indicating diminished economy of myocardial contraction. CEFF normalizes at 1 week, suggesting adequate compensation. TEFF is not altered in early AR. By 3 weeks, LV systolic dysfunction is accompanied by depressed TEFF, mechanical coupling, and CEFF signaling the onset of decompensated AR. Thus, volume overload of acute AR resulted in early compensation at the expense of myocardial efficiency with subsequent global dysfunction characterized by depressed LV systolic mechanics, mechanical, coupling, and contractile efficiencies.

Results of valve replacement with mechanical and biological prostheses in chronic renal dialysis patients.

BACKGROUND: Whether biological or mechanical valves should be used in patients on chronic dialysis therapy remains to be clearly defined. METHODS: A retrospective review was performed on 19 consecutive patients from our institution with end-stage renal disease on chronic peritoneal or hemodialysis undergoing aortic (n = 12), mitral (n = 5), or aortic-mitral (n = 2) valve replacement. RESULTS: The 9 biological and 10 mechanical valve patients had similar ages (56.5 versus 56.6 years) and cardiovascular risk factors. The overall estimated Kaplan-Meier survival was 60% +/- 12% at 12 months and 42% +/- 14% at 60 months. Mechanical valve patients had a significantly higher rate of postoperative cerebrovascular accidents or bleeding complications (10/10 versus 0/9; chi 2 = 17.0; p < 0.001). No subsequent reoperations were required for biological valve failure at a mean follow-up of 32 +/- 53 months. CONCLUSIONS: These results demonstrate that in patients with end-stage renal disease, use of mechanical valves is associated with significant risk of complications, whereas biological valve failure from prosthetic dysfunction is unusual. Overall survival is poor in both groups of patients. Therefore, preference should be given to biological valve instead of mechanical valve prostheses in patients on chronic renal dialysis.

Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair.

Myocardial repair after injury is limited because the adult heart cannot regenerate. We propose using autologous skeletal muscle cells (myoblasts) as a source of reserve cells for repair of regions of damaged myocardium. This report examines two potential methods for the transfer of cells to the myocardium: selective coronary catheterization, and myoblast infusion or myoblast injection directly into the left ventricular wall. Autologous, primary rabbit skeletal myoblasts were harvested, were transduced ex vivo with adenoviruses expressing the Escherichia coli beta-galactosidase (beta-gal) gene, and were infused selectively into the coronary circulation or injected directly into the myocardial wall. After either delivery method, beta-gal expression was detectable at the earliest times examined (3 days) and persisted for several weeks. The method of delivery influenced the spatial pattern of beta-gal expression. After direct injection, a localized concentration of myoblasts that decreased with distance from the injection site was visible primarily in the myocardial layer of the ventricle, although occasional staining could be detected in other layers. After coronary infusion, discrete punctate or linear foci of beta-gal expression were found throughout the distribution of the left coronary circulation in all cardiac layers. After infusion or injection, beta-gal-positive cells were seen in direct physical apposition to cardiocytes; interestingly, beta-gal could be detected also in some branched cells with clear cross-striations. Autologous myoblasts survived with no obvious dysrhythmic effects despite their presence in extensive or discrete loci in the myocardium. These observations provide the first evidence that myoblast transfer is possible by catheter-based methods, and they create the basis for studies to investigate the functional consequences of myoblast infusion in damaged heart.

Left ventricular adaptation to aortic regurgitation in conscious dogs.

OBJECTIVE: Cardiac failure as a result of valvular heart disease remains a major clinical problem that frequently leads to ventricular dysfunction, myocardial failure, and even death. The development of irreversible myocardial damage may be especially insidious in volume overload as a result of aortic or mitral regurgitation. METHODS AND RESULTS: Left ventricular wall volume, ventricular function, and myocardial performance were assessed in 10 chronically instrumented conscious dogs before and after creation of aortic regurgitation. Left ventricular wall volume was measured by serial echocardiography. Left ventricular function was assessed by total cardiac output, stroke work, the slope of the Frank-Starling relationship, and the slope of the end-systolic pressure-volume relationship. Myocardial performance was assessed by the slope of the myocardial power output versus end-diastolic strain relationship. End-diastolic wall stress and volume both increased acutely and remained elevated after creation of aortic regurgitation. Peak systolic wall stress increased initially (1 to 3 weeks) from 336 +/- 30 to 369 +/- 55 mm Hg but returned to control values as left ventricular wall volume increased from 78 +/- 13 to 88 +/- 16 ml after development of compensatory hypertrophy. Left ventricular systolic function remained constant or increased and was maintained initially by increased myocardial performance, which returned to baseline levels after the development of compensatory hypertrophy. CONCLUSIONS: Myocardial performance and ventricular function vary independently in aortic regurgitation. Measures of myocardial performance such as the myocardial power output versus end-diastolic strain relationship may be useful in clinical assessment of aortic regurgitation.

Alterations in hemodynamics and left ventricular contractility during carbon dioxide pneumoperitoneum.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum has been shown to adversely affect hemodynamics in patients. This study specifically examines the potential contribution of altered left ventricular contractility (LVC) to hemodynamic changes observed during CO2 pneumoperitoneum. METHODS: In a canine model, LV volumes, LV pressure, and intrathoracic and central venous pressures were recorded both at basal intra-abdominal pressure (IAP) and after CO2 insufflation to produce IAPs of 5-25 mmHg. RESULTS: At IAPs greater than 15 mmHg, cardiac output and LV end-diastolic volume decreased. Mean arterial pressure and heart rate were unchanged. LVC, quantified using the linear Frank-Starling relationship, was not affected by increases in IAP. CONCLUSIONS: This study is the first to quantify LVC during CO2 pneumoperitoneum and demonstrates no changes in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic alterations induced by CO2 pneumoperitoneum are secondary to altered LV preload and not alterations in contractility or LV afterload.

The in vivo quantification of myocardial performance in rabbits: a model for evaluation of cardiac gene therapy.

Evaluating cardiac gene therapy in the intact animal requires an index of cardiac function capable of detecting regional differences in contractility in a load-independent fashion. Potentially load-insensitive measures of ventricular performance were therefore evaluated in 10 open- and closed-chested, anesthetized rabbits. LV transmural pressure and myocardial segment length were measured using micromanometry and sonomicrometry during steady-state and transient inferior vena caval occlusion, over a range of inotropic and loading conditions. For each intervention, segmental stroke work was calculated as the area within the left ventricular transmural pressure-length loops at a given end-diastolic segment length during inferior vena caval occlusion; regression analysis was applied to obtain the linear Frank-Starling relationship. In both open- and closed-chested states, these relationships were highly linear (r = 0.97 +/- 0.1) and reproducible. The slope of the linear relationship between segmental stroke work and end-diastolic segment length increased significantly with calcium and epinephrine infusions (P < 0.05 v control) but was not significantly altered by decreased afterload or increased afterload (P > 0.4). The x-intercept was not significantly altered by changes in intropy or afterload (P > 0.4). These data validate the linear Frank-Starling relationship and the slope, MW, as a load-insensitive index of contractility in the intact rabbit. This study presents a novel approach to the quantification of regional cardiac function in smaller animals.