Improved survival rates support left ventricular assist device implantation early after myocardial infarction.

OBJECTIVES: Implantation of left ventricular assist devices (LVADs) early after acute myocardial infarction (MI) has traditionally been thought to be associated with high mortality rates due to technical limitations and severe end-organ dysfunction. At some experienced centers, doctors have refrained from earlier operation after MI to allow for a period of hemodynamic and end-organ stabilization. METHODS: We retrospectively investigated the effect of preoperative MI on the survival rates of 25 patients who received a Thermocardiosystems Incorporated LVAD either <2 weeks (Early) (n = 15) or >2 weeks (Late) (n = 10) after MI. Outcome variables included perioperative right ventricular assistance (and right-sided circulatory failure), hemodynamic indexes, percent transplanted or explanted, and mortality. RESULTS: No statistically significant differences were demonstrated between demographic, perioperative or hemodynamic variables between the Early and Late groups. Patients in the Early group demonstrated a lower rate of perioperative mechanical right ventricular assistance, but had a higher rate of perioperative inhaled nitric oxide use. In addition, 67% of patients in the Early group survived to transplantation and 7% to explantation, findings comparable to those in the Late group (60% and 0% respectively). CONCLUSIONS: This clinical experience suggests that patients may have comparable outcomes whether implanted early or late after acute MI. These data therefore support the early identification and timely application of this modality in post-MI LVAD candidates, as this strategy may also reveal a subgroup of patients for whom post-MI temporary LVAD insertion may allow for full ventricular recovery.

Synergy of amlodipine and angiotensin-converting enzyme inhibitors in regulating myocardial oxygen consumption in normal canine and failing human hearts.

The production of endogenous nitric oxide, which regulates myocardial oxygen consumption, is decreased in heart failure. As with angiotensin-converting enzyme (ACE) inhibitors, amlodipine, a calcium antagonist, increases kinin-mediated nitric oxide production in coronary microvessels. We investigated the possibility of synergy between ACE inhibitors and amlodipine in regulating myocardial oxygen consumption. Left ventricular myocardium was isolated from 6 healthy dog hearts and 5 human hearts with end-stage heart failure at the time of orthotopic heart transplantation. Myocardial oxygen consumption was measured before and after administration of bradykinin, S-nitroso N-acetyl penicillamine (SNAP, a nitric oxide donor), ramiprilat (an ACE inhibitor), amlodipine, and the combination of a sub-threshold dose of ramiprilat (10(-8) md/L) + amlodipine. These experiments were repeated with L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthesis), dichloroisocoumarin (an inhibitor of kinin synthesis), and HOE 140 (a B2 kinin-receptor antagonist). Baseline myocardial oxygen consumption in canine hearts was 182 +/- 21 nmol/g/min. Bradykinin and SNAP caused dose-dependent reductions in myocardial oxygen consumption (p <0.05). Ramiprilat and amlodipine caused a 10 +/- 3.2% and 11 +/- 0.8% reduction in myocardial oxygen consumption, respectively, when used alone (p <0.05). In the presence of a subthreshold dose of ramiprilat, amlodipine caused a larger (15 +/- 1.7%) reduction in myocardial oxygen consumption compared with either drug used alone (p <0.05). In human hearts, baseline myocardial oxygen consumption was 248 +/- 57 nmol/g/min. Amlodipine caused a larger reduction in myocardial oxygen consumption when used with ramiprilat (22 +/- 3.2%) as compared with amlodipine alone (15 +/- 2.6%). The effect of both drugs was attenuated by L-NAME, dichloroisocoumarin, and HOE 140 (p <0.05). In conclusion, ACE inhibitors and amlodipine act synergistically to regulate myocardial oxygen consumption by modulating kinin-mediated nitric oxide release, and this combination of drugs may be useful in the treatment of heart failure.

Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions.

The purpose of this paper is to describe an isolated heart model that uses human hearts to study cardiomyopathy. Techniques of organ preparation and perfusion are described that result in successful restoration of explanted human hearts to a beating condition. Native hearts of transplant recipients were placed on an isolated perfusion circuit immediately after explant. After appropriate organ and circuit preparation these hearts were restored to a functional state. Studies were done to assess the stability over time and response to inotropic stimulation. Six of seven hearts were returned to a functional condition. Left ventricular pressure generation ranged from 56 to 118 mm Hg (mean 84.8 +/- 34.11) at physiologic loading conditions. Hearts remained functional from 67 to 271 minutes (mean 152 +/- 71.7) and retained up to 70% of functional capacity after 120 minutes. Hearts performed in isovolumic and ejecting modes. Hearts had a marked response to inotrope administration not previously described. We conclude that human hearts can be reproducibly restored to a functional condition after explant from transplant recipients and can be maintained in a beating state with reasonably stable pressure generation for an extended period of time, which makes this a useful model with which to study cardiac pathophysiologic conditions. These hearts demonstrate an appropriate response to inotropes not previously observed, most likely because of improved myocardial preservation and stringent control of perfusate chemical make-up.

Systolic ventricular interaction in normal and diseased explanted human hearts.

OBJECTIVE: The purpose of this study was to quantify the magnitude of interaction between the right and left ventricles in conditions of heart failure. METHODS: Human hearts were taken from transplant recipients diagnosed with diluted cardiomyopathy at the time of transplantation and were restored to beating condition with use of an isolated perfusion circuit. Left ventricular-right ventricular interaction was determined by ramping volume in the left ventricle while holding right ventricular volume constant. Right ventricular pressure gain was plotted against left ventricular pressure and the slope of the linear regression determined the left ventricular-right ventricular interaction. A similar procedure was used to determine right ventricular-left ventricular interaction. Two normal hearts were obtained from transplant donors not suitable for cardiac donation to serve as control hearts. RESULTS: Mean left ventricular-right ventricular interaction was 0.22 in the hearts with dilated cardiomyopathy compared with 0.06 in the control hearts. Mean right ventricular-left ventricular interaction was 0.14 in the hearts with dilated cardiomyopathy compared with 0.09 in the control hearts. A marked increase in left ventricular-right ventricular interaction was noted in the hearts with dilated cardiomyopathy compared with control hearts. Although observed values of right ventricular-left ventricular interaction also correspond to previously published results, no significant increase was observed in the dilated cardiomyopathy condition. CONCLUSIONS: These studies confirm previously published values for systolic ventricular interaction obtained with animal models and demonstrate a marked increase in the dependence of the right ventricle on left ventricular function to maintain systolic pressure generation during conditions of dilated cardiomyopathy.

Desaturated venous-to-arterial shunting reduces right-sided heart failure after cardiopulmonary bypass.

BACKGROUND: Right-sided circulatory failure is a major cause of morbidity in heart transplant and ventricular assist device recipients. METHODS: Several systems for managing right-sided circulatory failure with use of a right-to-left shunt without need for an oxygenator or systemic heparinization were designed and used clinically. RESULTS: A right-to-left shunt was successfully used to treat severe right-sided circulatory failure in both a transplant and a left ventricular assist device recipient. CONCLUSIONS: If constructed between the femoral vein and artery, such a shunt could (1) be easily inserted and removed, (2) selectively infuse the lower extremities with desaturated blood while maintaining cerebral and cardiac perfusion with saturated blood, (3) selectively reduce the risk of paradoxical emboli to the head and heart, and (4) provide a known and adjustable degree of shunting depending on the condition of the patient, a major advantage of this system compared with creation of an atrial septal defect.

A microanalysis of ethanol-induced disruption of body sway and psychomotor performance in women.

Measures of body sway, psychomotor performance and subjective reports of intoxication were obtained from 20 women after consuming either ethanol (0.56 g/kg) or placebo. Simple motor tasks were unaffected by the relatively low ethanol dose. Performance on the Digit Symbol Substitution Test (DSST) was affected only during the ascending portion of the blood ethanol curve while stance stability was disrupted during peak and descending blood ethanol levels. A microanalysis of the dynamic changes of ethanol-induced body sway was conducted and the results plotted in three-dimensional space. These data revealed that disruption of stance stability was more pronounced in the sagittal plane than in the lateral plane and that subjects swayed to the rear and the right side. The results of this study suggest that such data analysis techniques provide extremely sensitive measures of body sway resulting from consuming a moderate dose of ethanol.

Surgical management of valvular disease in patients requiring left ventricular assist device support.

BACKGROUND: Success with long-term implantable left ventricular assist devices (LVAD) has led to increased use in patients previously thought to be unsuitable for mechanical circulatory assistance. Patients with preexisting or newly diagnosed valvular disease have been traditionally excluded from device placement. The purpose of this study was to review our experience with LVAD support in patients with valvular disease and to develop a management algorithm for these difficult patients. METHODS: We reviewed the clinical records of 199 consecutive patients who received the ThermoCardiosystems, Inc, HeartMate Pneumatic or Vented Electric LVAD. There were 18 patients (9%) who required surgical management of native or prosthetic valvular disease during LVAD implantation. RESULTS: Suture or patch closure of the aortic valve was performed in 6 patients, aortic valve plication and repair in 1 patient, mitral valve repair in 4 patients, and tricuspid valve annuloplasty in 5 patients. Two patients with mechanical mitral valve prostheses were treated with postoperative warfarin anticoagulation. Fifteen of the 18 patients with valvular pathology survived the immediate postoperative period (17% mortality). Eleven patients have either undergone transplantation or continue to be supported with an LVAD (61%). Operative mortality in LVAD patients without concomitant valve repair was 18% (n = 33) with a late mortality of 7% (n = 13). Seven of these late deaths occurred in patients who received a device as destination therapy. In the remaining 6 patients, the cause of death was sepsis (n = 2), multisystem organ failure (n = 2), driveline rupture (n = 1), and massive gastrointestinal bleed (n = 1). CONCLUSIONS: Preexisting native or prosthetic valve pathology does not increase the immediate perioperative risk of LVAD insertion; however, these patients continue to pose a challenge for postoperative management while awaiting transplantation.

Low thromboembolic risk without anticoagulation using advanced-design left ventricular assist devices.

BACKGROUND: A major limitation of cardiac assist devices has been the high incidence of thromboembolic events and their requirement for systemic anticoagulation. The Thermo Cardiosystems HeartMate 1000 IP left ventricular assist device (LVAD) employs a design that may reduce thromboembolic risk and obviate the need for systemic anticoagulation. METHODS: Two hundred twenty-three patients with nonreversible heart failure were supported with the HeartMate LVAD as a bridge to heart transplantation. All patients were monitored prospectively for thromboembolic events. Anticoagulation regimens and occurrence of subclinical thromboembolic events, including those seen by transcranial Doppler examinations in selected patients, were also recorded. RESULTS: Total time of LVAD support use was 531.2 patient-months. Twenty-three patients (10%) received warfarin postoperatively for 42.4 patient-months (8.2% of total support time). Six patients (2.7%) had thromboembolic events, representing 0.011 events per patient-month of device use. CONCLUSIONS: The thromboembolic complication rate associated with this LVAD is acceptably low despite the minimal anticoagulation employed in this series, allowing consideration of long-term device use for the treatment of heart failure.

Right-to-left veno-arterial shunting for right-sided circulatory failure.

BACKGROUND: Right-sided circulatory failure, a complication of heart transplantation and left ventricular assist device use, results in decreased cardiac output due to diminished flow across the pulmonary circuit. We hypothesized that creation of a controlled right-to-left shunt would result in decompression of the right ventricle and improved systemic cardiac output at tolerable oxygen saturations. We also hypothesized that a peripheral veno-arterial shunt is physiologically superior to a central shunt. METHODS: Right atrial-femoral artery and right atrial-left atrial shunts were created in a large animal model (calf). Right-sided circulatory failure was induced by banding the pulmonary artery. Hemodynamic measures and blood gas determinations were obtained during nonshunted and shunted states. RESULTS: Peripheral and central shunts resulted in decreased right-sided pressures and increased cardiac output. Arterial oxygen saturation remained greater than 90% during shunting. The peripheral shunt had the added advantage of decreasing left ventricular end-diastolic pressure and left ventricular stroke work. CONCLUSIONS: A controlled right-to-left shunt improved hemodynamics and cardiac output in a large animal model with right-sided circulatory failure. This strategy may be useful in the management of transplant and left ventricular assist device recipients with perioperative right-sided circulatory failure. Our studies also indicate that creation of a peripheral shunt has both physiologic and technical advantages over a central shunt.

Blood ethanol levels, self-rated ethanol effects and cognitive-perceptual tasks.

Family history of alcoholism influences the acute effects of ethanol in young men. We expanded these findings by concomitantly measuring plasma ethanol levels (BALs), subjective intoxication effects, and task performance in young women. Healthy subjects with no familial alcoholism provided informed consent and received 0.75 ml/kg ethanol or isocaloric placebo (n = 10 per group) under randomized double-blind conditions. Assessments were made at 90, 60 and 30 min before, and 15, 30, 45, 60, 90, 120, 150 and 180 min after beverage administration. BALs reached 80 mg/dl 45-60 min following ethanol. Dizziness and clumsiness ratings correlated strongly with BAL, but clumsiness and confusion were the strongest effects associated with placebo. Impaired visual selectivity and hand-eye coordination covaried with BAL (p less than 0.05) on written tests. Deficits in abstract instruction and symbol comprehension almost attained statistical significance (p less than 0.06). Compared with previous findings for males, data from the present report suggest that ethanol may have gender-related effects.

Venoarterial shunting for the treatment of right sided circulatory failure after left ventricular assist device placement.

Right sided circulatory failure (RSCF), a common complication after left ventricular assist device (LVAD) implantation, results in decreased systemic output due to diminished blood flow across the pulmonary vasculature. The authors hypothesized that creation of a venoarterial shunt (VAS) would decompress the right-sided circulation and improve systemic pressure and perfusion with significant arterial desaturation. An experimental model was created in which RSCF was induced acutely in a large animal (n = 6) by beta-blockade after LVAD placement. After VAS creation, hemodynamic and blood gas determinations were performed to compare non shunt and shunt states. After induction of heart failure after LVAD placement, VAS resulted in a 22% elevation in systemic blood pressure (p < 0.0001), a 36% elevation in cerebral blood flow (p = 0.02), and an 18% decrease in right sided filling pressures (p = 0.08). Systemic pH and aortic oxygen saturation remained unchanged from baseline. In a large animal model of RSCF after LVAD implantation, VAS improves systemic hemodynamics without a significant cost in arterial oxygenation to critical organs and without creating acid-base imbalance. Beside implementation, adjustable capabilities, easy removal and salutatory hemodynamic effects suggest that VAS may serve as a first line, short-term therapy for LVAD recipients who develop perioperative RSCF.

Patient evaluation of the hotel function of hospitals.

BACKGROUND: A means of measuring patient satisfaction is essential in the effort to improve the quality of health care delivered in our nation's hospitals. Accurate feedback allows employers to better meet patients' needs and allows hospital administrators to improve service delivery. Patients are empowered by having a voice in the manner in which their health care is delivered. Moreover, improving the efficiency of the health care delivery system decreases health care costs. Hospital comparisons can be made readily available to a large audience through the Internet, resulting in empowerment of the patient and a universal improvement in hospital care. This is the first multi-institutional analysis of patient satisfaction among New York City and northern New Jersey area tertiary care hospitals. In this study, we evaluated the patient-assessed hotel function of hospitals in a single geographic region to determine whether clinically and statistically significant differences would be revealed that could provide beneficial information to stakeholders in the healthcare system. METHODS: Patients (n = 261) who had spent a night during the past year in one of eleven hospitals within 60 miles of New York City were chosen at random from doctors' waiting rooms. On average, 24 patients from each hospital were surveyed. They were asked to complete a questionnaire that rated the various departments in the hospital on qualities such as courtesy, promptness, and cleanliness. The questionnaire also rated important characteristics of the patient experience, such as the ease of parking and the taste of the food. Each item on the survey was coded on a scale of 1 to 10 with 10 being the most positive response. The 26 specific questions were divided into 14 domains. Averages in each domain were compared by gender, age, and hospital identity, attractiveness, and setting. All statistical calculations were performed using SPSS/PC, and means were compared using t-tests. RESULTS: Analysis designed to evaluate outcomes between each of the possible 54 pairs of hospitals comparisons revealed statistically significant differences as often as 44% of the time in some outcomes measures (logistics), but as rarely as 7% of the time in others (billing function). Clinically significant differences (>2 units per scale) were frequently evident, although the ranges differed dramatically depending on the domains surveyed. Although age, gender, and race/ethnicity were generally not predictive of satisfaction, non-urban setting was correlated with greater patient satisfaction. CONCLUSION: By having access to patient satisfaction comparisons among hospitals, patients are empowered to make better choices, employers can identify and adapt to patient preferences, and administrators can improve the services delivered and decrease health care costs by improving efficiency. Although our study was somewhat limited by patient selection biases, the study's results suggest that Internet-based tools of comparison will enable patients to make free and informed decisions about their health care by comparing local hospitals and voting on their impressions of the facilities from which they receive care.

Creation of a controlled venoarterial shunt. A surgical intervention for right-side circulatory failure.

BACKGROUND: Right-side circulatory failure (RSCF), a common complication of heart transplant and left ventricular assist device recipients, results in decreased cardiac output because of diminished flow across the pulmonary circuit. We hypothesized that creation of a controlled venoarterial shunt would result in decompression of the right ventricle and improved systemic cardiac output at tolerable oxygen saturations. METHODS AND RESULTS: A venoarterial shunt was created in a large-animal model (calf, n = 6). RSCF was induced by banding the pulmonary artery. Hemodynamic measures and blood gas determinations were obtained during nonshunted and shunted states. Pulmonary artery banding increased mean right ventricular systolic pressure from 44.9 +/- 2.1 mm Hg (mean +/- SEM) to 85.9 +/- 6.9 mm Hg (P < .05, paired t test) and decreased mean aortic flow from 7.8 +/- 1.0 to 4.2 +/- 1.1 L/min (P < .05). Flow through a venoarterial shunt at approximately 40% of cardiac output resulted in a decrease in right ventricular end-systolic pressure from 85.9 +/- 6.9 to 72.1 +/- 5.6 mm Hg (P < .01, ANOVA), a decrease in mean pulmonary artery pressure from 42.9 +/- 5.0 to 37.2 +/- 3.8 mm Hg (P < .01), and an increase in aortic flow from 4.2 +/- .05 to 5.1 L/min (P < .01). Left ventricular stroke work decreased from 2.22 +/- 0.28 to 1.55 +/- 0.88 (P < .05). Carotid artery oxygen saturation did not change significantly (99.9 +/- .02 to 97.6 +/- 1.7) during shunting. CONCLUSIONS: A controlled venoarterial shunt improved hemodynamics and cardiac output in a large animal model with RSCF. This strategy may be useful in the management of transplant and left ventricular assist device recipients with perioperative RSCF.

Discriminating between preservation and reperfusion injury in human cardiac allografts using heart weight and left ventricular mass.

BACKGROUND: Myocardial edema caused by injury during preservation or reperfusion can affect cardiac function after heart transplantation. This study was designed to distinguish these forms of injury in human allografts. METHODS AND RESULTS: In 15 donor hearts preserved in University of Wisconsin solution, heart weight (HW) was obtained immediately after explantation and after transport before implantation. Left ventricular mass (LVM) was calculated separately in 18 patients with the use of epicardial two-dimensional echocardiograms obtained both before explantation from the donor and after transplantation and weaning from cardiopulmonary bypass. While changes in LVM could be due to preservation or reperfusion injury, changes in HW can only be due to edema occurring during transport. HW averaged 339 +/- 24 g (mean +/- SE) before and 340 +/- 24 g after transport (P = NS); however, LVM increased 14 g, from 164 +/- 8 to 178 +/- 11 g (P < .05, paired t test). LVM increased in 10 of 18 patients (56%). No correlation was demonstrated between duration of ischemia (mean, 172 +/- 13 minutes) and changes in HW or LVM. Two patients died as a result of primary graft failure. In the first, HW increased 54 g, 2 SD above the mean. In the second, LVM increased 66 g, 2 SD above the mean, but HW changed minimally. CONCLUSIONS: While current preservation methods result in minimal change in HW during transport, reperfusion injury frequently increases LVM. LVM determination by two-dimensional echocardiography may prove valuable in detecting allograft injury.