Evolution of concomitant use of veno-arterial extracorporeal membrane oxygenation support with Impella in cardiogenic shock: From percutaneous femoral Impella to axillary Impella 5.5.

BACKGROUND: Little is known about safety and efficacy of the use of Impella 5.5 compared to previous iterations in the setting of Impella with Veno-Arterial Extracorporeal Membrane Oxygenation Support as ECPELLA. METHODS: Consecutive patients who were treated by ECPELLA with surgically implanted axillary Impella 5.5 (N = 13) were compared with patients supported by ECPELLA with percutaneous femoral Impella CP or 2.5 (Control, N = 13). RESULTS: The total ECPELLA flow was higher in ECPELLA 5.5 group (6.9 vs. 5.4 L/min, p = 0.019). Actual hospital survival was higher than predicted and comparable in both groups (ECPELLA 5.5, 61.5% vs. Control, 53.8%, p = 0.691). Both total device complications (ECPELLA 5.5, 7.7% vs. Control, 46.1%, p = 0.021) and Impella-specific complications (ECPELLA 5.5, 0% vs. Control, 30.8%, p = 0.012) were significantly lower in the ECPELLA 5.5 group. CONCLUSIONS: Utilization of Impella 5.5 in the setting of ECPELLA provides greater hemodynamic support with a lower risk of complications compared to Impella CP or 2.5.

An Update on the Diagnosis and Management of Acute Right Heart Failure.

Right ventricular (RV) dysfunction and resultant acute right heart failure (ARHF) is a rapidly growing field of interest, driven by increasing appreciation of its contribution to heart failure morbidity and mortality. Understanding of ARHF pathophysiology has advanced dramatically over recent years and can be broadly described as RV dysfunction related to acute changes in RV afterload, contractility, preload, or left ventricular dysfunction. There are several diagnostic clinical signs and symptoms as well as imaging and hemodynamic assessments that can provide insight into the degree of RV dysfunction. Medical management is tailored to the different causative pathologies, and in cases of severe or end-stage dysfunction, mechanical circulatory support can be utilized. In this review, we describe the pathophysiology of ARHF, how its diagnosis is established by clinical signs and symptoms and imaging findings, and provide an overview of treatment options, both medical and mechanical.

Simple technique of distal leg perfusion during heart transplant in patients with preoperative veno-arterial extracorporeal membrane oxygenation support.

Direct heart transplant from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is challenging. Continuation of postoperative VA-ECMO support may be required in the setting of primary graft dysfunction or severe vasoplegia. We describe a simple technique to perfuse the ipsilateral leg of an arterial ECMO cannula during heart transplant while the ECMO circuit is turned off but maintaining the arterial cannula and distal perfusion catheter in place. This technique minimizes the number of intraoperative procedures with a minimal risk of leg ischemia, and provides a smooth transition to postoperative VA-ECMO support if necessary.

COVID-19, Heart Failure Hospitalizations, and Outcomes: A Nationwide Analysis.

Heart Failure (HF) patients are at a higher risk of adverse events associated with Coronavirus disease 2019 (COVID-19). Large population-based reports of the impact of COVID-19 on patients hospitalized with HF are limited. The National Inpatient Sample database was queried for HF admissions during 2020 in the United States (US), with and without a diagnosis of COVID-19 based on ICD-10-CM U07. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 1,110,085 hospitalizations for HF were identified of which 7,905 patients (0.71%) had a concomitant diagnosis of COVID-19. After propensity matching, HF patients with COVID-19 had higher rate of in-hospital mortality (8.2% vs 3.7%; odds ratio [OR]: 2.33 [95% confidence interval [CI]: 1.69, 3.21]; P< 0.001), cardiac arrest (2.9% vs 1.1%, OR 2.21 [95% CI: 1.24,3.93]; P<0.001), and pulmonary embolism (1.0% vs 0.4%; OR 2.68 [95% CI: 1.05, 6.90]; P = 0.0329). During hospitalizations for HF, COVID-19 was also found to be an independent predictor of mortality. Further, increasing age, arrythmias, and chronic kidney disease were independent predictors of mortality in HF patients with COVID-19. COVID-19 is associated with increased in-hospital mortality, longer hospital stays, higher cost of hospitalization and increased risk of adverse outcomes in patients admitted with HF.

Cannulation-related adverse events of peripheral veno-arterial extracorporeal membrane oxygenation support in heart transplantation: Axillary versus femoral artery cannulation.

BACKGROUND: In heart transplantation (HT), peripheral veno-arterial extracorporeal membranous oxygenation (VA-ECMO) is utilized preoperatively as a direct bridge to HT or postoperatively for primary graft dysfunction (PGD). Little is known about wound complications of an arterial VA-ECMO cannulation site which can be fatal. METHODS: From 2009 to 2021, outcomes of 80 HT recipients who were supported with peripheral VA-ECMO either preoperatively or postoperatively were compared based on the site of arterial cannulation: axillary (AX: N = 49) versus femoral artery (FA: N = 31). RESULTS: Patients in the AX group were older (AX: 59 years vs. 52 years, p = .006), and less likely to have extracorporeal cardiopulmonary resuscitation (0% vs. 12.9%, p = .040). Survival to discharge (AX, 81.6% vs. FA. 90.3%, p = .460), incidence of stroke (10.2% vs. 6.5%, p = .863), VA-ECMO cannulation-related bleeding (6.1% vs. 12.9%, p = .522), and arm or limb ischemia (0% vs. 3.2%, p = .816) were comparable. ECMO cannulation-related wound complications were lower in the AX group (AX, 4.1% vs. FA, 45.2%, p < .001) including the wound infections (2.0% vs. 32.3%, p < .001). In FA group, all organisms were gram-negative species. In univariate logistic regression analysis, AX cannulation was associated with less ECMO cannulation-related wound complications (Odds ratio, .23, p < .001). There was no difference between cutdown and percutaneous FA insertion regarding cannulation-related complications. CONCLUSIONS: Given the lower rate of wound complications and comparable hospital outcomes with femoral cannulation, axillary VA-ECMO may be an excellent option in HT candidates or recipients when possible.

Survival With Continuous Outpatient Intravenous Inotrope Therapy in the Modern Era.

BACKGROUND: To describe baseline characteristics and outcomes in the largest known registry of advanced heart failure (HF) patients receiving continuous outpatient intravenous inotrope therapy. Studies evaluating the use of outpatient inotropes for palliation or as a bridge to advanced therapies were performed before current guideline directed medical and device therapy (GDMDT). There are limited data on the modern experience using outpatient inotrope (OI) therapy. STUDY QUESTION: We aimed to study current use and outcomes of OI. STUDY DESIGN: Retrospective database analysis. MEASURES AND OUTCOMES: From 2015 to 2017, 1540 advanced HF patients in a largess nationwide registry received OI with either milrinone or dobutamine. Baseline characteristics of 1149 patients data were retrospectively reviewed. Unadjusted Kaplan-Meier survival estimates censored at the time of transplant or mechanical circulatory support were reported. RESULTS: Of 1149 patients, more patients were treated with milrinone than dobutamine (64.6% vs. 35.4%). Regardless of the indication for OI, estimated 1 and 2-years survival was 61.8% and 41.6%, respectively. Milrinone use was associated with a greater 1-year survival than dobutamine (70.7% vs. 46.2%, P < 0.0001). The superiority of milrinone over dobutamine extended to all indications for OI, including bridge to transplant (85.9% vs. 71.3%, P < 0.0001), bridge to mechanical support (91.4% vs. 71%, P = 0.001), and palliation (73.6% vs. 63.3%, P < 0.001). After adjusting for indication, age, gender and weight, milrinone was associated with lower mortality than dobutamine (HR 0.50, 95% CI 0.39-0.64, P < 0.0001). CONCLUSIONS: In the largest dataset of HF patients receiving OI, survival on OI for palliation in the current era of GDMDT is significantly higher than previously reported. Compared with dobutamine, milrinone was associated with improved survival in all cohorts.

Mineralocorticoid Receptor Antagonist Use in Heart Failure With Reduced Ejection Fraction and End-Stage Renal Disease Patients on Dialysis: A Literature Review.

Mineralocorticoid receptor antagonists (MRAs) are known to have a proven mortality benefit in heart failure with reduced ejection fraction (HFrEF) without kidney disease. As patients with end-stage renal disease (ESRD) requiring either peritoneal dialysis or hemodialysis were excluded in clinical trials of HFrEF, the data are scant on the appropriate use of MRAs in this population. The unknown efficacy, along with concerns of adverse effects such as hyperkalemia, has limited the willingness of clinicians to consider using MRAs in these patients. However, it is unclear whether the risk of hyperkalemia is present if a patient is oliguric or anuric. Current guidelines recommend against the use of MRAs in patients with chronic kidney disease, but do not address the use of MRAs in patients requiring dialysis. This article will review the epidemiology of heart failure in ESRD, the pathophysiological derangements of the renin-angiotensin-aldosterone system in patients with kidney disease, and the results from case series and trials of the use of MRAs in ESRD with HFrEF. Although limited to several small trials using MRAs in peritoneal and hemodialysis patients with or without HFrEF, the current literature appears to show the potential for clinical benefits with little risk.

Management of pulmonary hypertension from left heart disease in candidates for orthotopic heart transplantation.

Pulmonary hypertension in left heart disease (PH-LHD) commonly complicates prolonged heart failure (HF). When advanced, the PH becomes fixed or out of proportion and is associated with increased morbidity and mortality in patients undergoing orthotopic heart transplant (OHT). To date, the only recommended treatment of out of proportion PH is the treatment of the underlying HF by reducing the pulmonary capillary wedge pressure (PCWP) with medications and often along with use of mechanical circulatory support. Medical therapies typically used in the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) have been employed off-label in the setting of PH-LHD with varying efficacy and often negative outcomes. We will discuss the current standard of care including treating HF and use of mechanical circulatory support. In addition, we will review the studies published to date assessing the efficacy and safety of PAH medications in patients with PH-LHD being considered for OHT.

Unilateral Headache Status after Intra-Aortic Balloon Pump Placement.

INTRODUCTION: Intra-aortic balloon pump (IABP) counterpulsation is a catheter-based treatment for coronary artery disease and decompensated heart failure to increase coronary blood flow and improve cardiac output. IABP is generally well tolerated, and complications are usually related to peripheral vasculature or red blood cell and platelet consumption. The usual insertion site via femoral artery renders the patient bedbound. Recently, axillary artery has been used in patients with atherosclerotic peripheral vascular disease and documented small arteries or in those awaiting transplant to ensure ambulation and prevent deconditioning. CASE REPORT: We present a patient with ischemic cardiomyopathy and severe left ventricular dysfunction, awaiting Orthotropic Heart Transplant. His worsening intractable angina and dyspnea necessitated IABP placement via left axillary artery, significantly improving his condition. He subsequently experienced migraine-type persistent unilateral headache refractory to standard pain management. Multiple strategies were utilized to treat his pain, but the patient insisted that his pain commenced after IABP placement. Ultimately, the removal of the pump led to complete resolution with no recurrence. CONCLUSION: The authors hypothesize that the unilaterally directed blood flow and direct increase in cerebral perfusion from the intra-aortic balloon pump may have caused vasodilation of the extracranial arteries, leading to a persistent and debilitating headache in this susceptible patient.

Cardiac Transplantation in the New Era.

The prevalence of heart failure continues to rise due to the aging population and longer survival of people with conditions that lead to heart failure, eg, hypertension, diabetes, and coronary artery disease. Although medical therapy has had an important impact on survival of patients and improving quality of life, heart transplantation remains the definitive therapy for patients that eventually deteriorate. Since the first successful heart transplantation in 1967, significant improvements have been made regarding donor and recipient selection, surgical techniques, and postoperative care. However, the number of potential organ donors has not changed and the growing number of patients in need for transplantation has resulted an increase in waiting list time, and the need for mechanical support. To overcome this issue, the United Network for Organ Sharing implemented an allocation system to prioritize the sickest patients on the list to receive organs. Despite the careful selection of patients, pretransplant immunological screening, and multidrug immunosuppressive regimens, acute and chronic rejections occur and potentially limit graft and patient survival. Treatment for rejection largely depends on the type of rejection, the presence of hemodynamic compromise, and time after transplantation. The limiting factor for long-term graft survival is allograft vasculopathy, an immune-mediated process causing diffuse narrowing of the coronary arteries. Percutaneous coronary intervention and coronary artery bypass surgery are often not an option for this vasculopathy due to the lack of focal lesions, and retransplantation is the only option in appropriate patients.

Pretransplant coagulopathy and in-hospital outcomes among heart transplant recipients: a propensity-matched nationwide inpatient sample study.

BACKGROUND: The prevalence and contemporary trends of pre-heart transplantation (HT) coagulopathy and associated clinical outcomes have not been studied from a national database. HYPOTHESIS: Pre-HT coagulopathy is associated with increased in-hospital mortality. METHODS: Among 2454 adult HT recipients from the 2003 to 2010 Nationwide Inpatient Sample databases, 707 (29%) had pre-HT coagulopathy (defined as a comorbidity variable, based on International Classification of Diseases, Ninthe Revision, Clinical Modification and Diagnosis Related Group codes). We used propensity scores for coagulopathy to assemble a matched cohort of 664 pairs of patients with and without coagulopathy balanced in 54 baseline characteristics. RESULTS: The prevalence of pre-HT coagulopathy increased from 17% in 2003 to 44% in 2010 (P for trend <0.001). In-hospital mortality occurred in 8.6% and 4.7% of matched HT recipients with and without coagulopathy, respectively (hazard ratio: 1.81; 95% confidence interval [CI]: 1.17-2.80; P = 0.008). Coagulopathy was not significantly associated with post-HT graft complications (odds ratio [OR]: 1.20; 95% CI: 0.95-1.52; P = 0.131) but was associated with increased blood transfusions (OR: 1.92; 95% CI, 1.54-2.41; P < 0.001). Coagulopathy and no-coagulopathy groups had no difference in median length of stay (22 days in each group, P = 0.746), but median total hospital charges were higher among patients with coagulopathy compared to those without (US$425 643 vs US$389 656; P = 0.008). CONCLUSIONS: In this national study of HT recipients, pretransplant coagulopathy was common, increased over time, and was not significantly associated with post-HT graft complications or increased hospital stay. However, it was associated with increased bleeding risk, in-hospital mortality, and total hospital charges. These findings may have implications for the selection of patients for HT.

Combination use of a TandemHeart with an extracorporeal oxygenator in the treatment of five patients with refractory cardiogenic shock after acute myocardial infarction.

Cardiogenic shock remains the leading cause of in-hospital death for patients admitted with acute myocardial infarction. For patients with refractory cardiogenic shock, early revascularization and intra-aortic balloon pump support are often inadequate to reverse the persistent circulatory collapse. We report 5 cases in which an extracorporeal oxygenator in series with the TandemHeart system was instituted emergently in patients with refractory cardiogenic shock from acute myocardial infarction. From our experience, we showed that the device can be safely and easily inserted and that it is able to reverse circulatory collapse and provide hemodynamic stability in patients who otherwise have a high mortality rate.

Peripheral extracorporeal membrane oxygenation: comprehensive therapy for high-risk massive pulmonary embolism.

BACKGROUND: Although commonly reserved as a last line of defense, experienced centers have reported excellent results with pulmonary embolectomy for massive and submassive pulmonary embolism (PE). We present a contemporary surgical series for PE that demonstrates the utility of peripheral extracorporeal membrane oxygenation (pECMO) for high-risk surgical candidates. METHODS: Between June 2005 and April 2011, 29 patients were treated for massive or submassive pulmonary embolism, with surgical embolectomy performed in 26. Four high-risk patients were placed on pECMO, established by percutaneously cannulating the right atrium through a femoral vein and perfusing by a Dacron graft anastomosed to the axillary artery. A small, extracorporeal, rotary assist device was used, interposing a compact oxygenator in the circuit, and maintaining anticoagulation with heparin. RESULTS: Extracorporeal membrane oxygenation was weaned in 3 of 4 patients after 5.3 days (5, 5, and 6), with normalization of right ventricular dysfunction and pulmonary artery pressure (44.0 ± 2.0 to 24.5 ± 5.5 mm Hg) by ECHO. Follow-up computed tomographies showed several peripheral, nearly resorbed emboli in 1 case and complete resolution in 2 others. The fourth patient, not improving after 10 days, underwent surgery where an embolic liposarcoma was extracted. For all 29 cases, hospital and 30-day mortality was 0% and all patients were discharged, with average postoperative length of stay of 15 days for embolectomy and 17 days for pECMO. CONCLUSIONS: Heparin therapy with pECMO support is a rapid, effective option for patients who might benefit from pulmonary embolectomy but are at high risk for surgery.

A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.

BACKGROUND: Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. METHODS AND RESULTS: One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank). CONCLUSIONS: Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00299221.

Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial).

BACKGROUND: Prior retrospective studies have suggested that tacrolimus monotherapy is an option associated with excellent outcomes and reduced toxicities. METHOD: We conducted a prospective, randomized, 2-center study of tacrolimus combination therapy vs monotherapy. From April 16, 2004, to September 15, 2005, 58 adult heart transplant patients were studied. All received oral tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were then randomized to a group where mycophenolate was maintained (COMBO) or to a group where it was discontinued (MONO) 14 days post-transplant. Corticosteroids were rapidly withdrawn in both groups between 8 and 12 weeks. RESULT: The primary end point (mean 6-month International Society of Heart and Lung Transplantation biopsy score) was 0.44 +/- 0.04 in the MONO group and 0.60 +/- 0.05 in the COMBO group (p = 0.013, unpaired Student's t-test). The freedom from rejection grade of 2R or higher at 6 and 12 months was 93.3% with MONO and 92.9% with COMBO (p = NS). CONCLUSION: Tacrolimus monotherapy appears to be safe and efficacious in heart transplant recipients and is not associated with excess rejection in the first year post-transplant. Further studies of this approach are warranted.

Is toxoplasmosis prophylaxis necessary in cardiac transplantation? Long-term follow-up at two transplant centers.

Cardiac transplant recipients are often given prophylactic treatments to prevent opportunistic infections such as Pneumocystis carinii. Toxoplasmosis prophylaxis is commonly prescribed for transplant recipients who have not been exposed to this disease but receive a heart from an exposed donor. We reviewed the collective 28-year experience at two urban transplant programs with 596 patients, and found no cases of toxoplasmosis, but all patients received trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia. We conclude that specific anti-toxoplasmosis prophylaxis is unnecessary in heart transplant recipients.

Long-term results of tacrolimus monotherapy in cardiac transplant recipients.

BACKGROUND: Conventional immunosuppression for heart transplantation is associated with various adverse effects. Tacrolimus monotherapy (TM) is an alternative strategy that minimizes exposure to additional immunosuppressants. METHODS: We retrospectively reviewed clinical data for all adult transplant recipients between January 1, 1996 and May 1, 2004. Clinical outcomes were analyzed according to immunosuppressive regimen. RESULTS: A total of 167 heart transplants were performed at our center. Eight patients died before receiving calcineurin inhibitors and were excluded from analysis. The mean follow-up for the 159 surviving patients was 1,520 +/- 78 days. Ninety of 124 patients initially treated with tacrolimus and corticosteroids were weaned to TM without the use of an anti-proliferative agent (Group A), resulting in an overall success rate of 75% at an average of 271 +/- 18 days after transplant. The remaining 69 recipients were treated with other tacrolimus- or cyclosporine-based regimens (Group B). Survival was significantly greater in Group A. The prevalence of high-grade rejection within the first year and incidence of cardiac allograft vasculopathy were similar between groups. Ten patients (11%) in Group A required recommencement of combination immunosuppression at an average of 768 +/- 772 days. CONCLUSIONS: TM is achievable in the majority of cardiac transplant recipients. Patients who tolerated reduced immunosuppression enjoyed greater survival than those treated with other regimens, without additional high-grade rejection or vasculopathy. These promising results remain to be confirmed in a prospective trial.

Lack of sensitization and equivalent post-transplant outcomes with the Novacor left ventricular assist device.

BACKGROUND: Ventricular assist devices (VADs) are increasingly used to support critically ill heart failure patients awaiting transplantation. Previous work has focused on the Thoratec Heartmate VE device, use of which is associated with pre-formed antibody production. We reviewed our cumulative experience with the Worldheart Novacor VAD as a bridge to transplantation (BTT). METHODS: From January 1989 through October 2002, 39 patients required a VAD bridge, with 26 of 39 surviving to transplantation. Antibody levels were assessed by complement-dependent cytotoxicity assay at routine intervals and expressed as panel reactive antibody (PRA) levels. Post-transplant allograft rejection, coronary vasculopathy, and survival were compared between Novacor-supported patients and non-VAD transplant recipients. RESULTS: PRA values did not significantly change after VAD implantation (12.4% +/- 11.2% vs 14.8% +/- 12.3%, p = 0.28). Survival for the BTT patients was 80.4%, 75.7%, 64.0%, 64.0%, and 64.0%, respectively, for 1, 3, 5, 7, and 10 years post-transplant, with similar results for non-BTT patients. The freedom from coronary vasculopathy was 90.2%, 90.2%, 72.2%, and 72.2%, respectively, at 1, 3, 5, and 7 years post-transplant. CONCLUSIONS: First, to our knowledge, this study is the first to examine the incidence of allosensitization after Novacor implant in detail. In contrast with previous results of work with other VAD systems, as assessed by PRA levels, Novacor patients did not become sensitized. Second, compared with 220 non-BTT patients who received transplants during a similar time frame, Novacor BTT patients had equivalent rejection profiles and survival. Finally, the incidence of transplant-associated coronary artery disease was lower than in previous reports.

Calcineurin inhibitor-associated early renal insufficiency in cardiac transplant recipients: risk factors and strategies for prevention and treatment.

Cardiac transplantation is the definitive treatment for eligible patients with end-stage cardiac failure. Techniques have evolved to reduce surgical mortality to under 5%. Immediate and subsequent long-term survival is more dependent on acute and chronic rejection and the complications of immunosuppressive therapy. Ten-year survival is greater than 50%.The success of transplantation over the last 20 years has been largely due to the advances in immunosuppression. The most notable and dramatic milestone was the introduction of cyclosporine in the early 1980s, which resulted in a significant improvement in allograft and patient survival. Cyclosporine is a peptide that inhibits the immune system by suppressing T-helper cell activation via inhibition of calcineurin, a critical intracellular enzyme. Tacrolimus has a similar (but not identical) mechanism of action, and was introduced in the 1990s. Drugs such as cyclosporine and tacrolimus, generically referred to as calcineurin inhibitors, have become the cornerstones of immunosuppressive protocols. As a group, calcineurin inhibitors have adverse effects, including neurotoxicity, hypertension, and nephrotoxicity, which complicate their use. Early renal insufficiency manifests as postoperative oliguria (<50 mL/h urine output) or rising serum creatinine levels. There are a variety of postulated causes for calcineurin inhibitor-associated early renal insufficiency including direct calcineurin inhibitor-mediated renal arteriolar vasoconstriction, increased levels of endothelin-1 (a potent vasoconstrictor), as well as decreased nitric oxide production and alterations in the kidney's ability to adjust to changes in serum tonicity. Once early renal insufficiency occurs, no single treatment has been shown to be effective. Approaches discussed in this paper include reduction in calcineurin inhibitor dosages, as well as various drugs to promote increased renal perfusion such as misoprostol and dopamine. In addition, the paper emphasizes the importance of ruling out other causes of renal insufficiency in the early postoperative period, including volume depletion, depressed cardiac output, and mechanical obstruction to urine flow. Given that there is no highly efficacious treatment for this syndrome, ways to avoid its occurrence are desirable. One paper is referenced that suggests that avoidance of rapid changes in tacrolimus level during the first three days of therapy is associated with a low occurrence of early renal insufficiency.

Recent improvements in outcome with the Novacor left ventricular assist device.

BACKGROUND: The Novacor implantable, electrically powered, wearable, left ventricular assist device (LVAD) has been used as a bridge to transplantation at our institution since 1994. Recent changes in protocol have resulted in a decreased incidence of infections, thromboembolism, and mortality. METHODS: We reviewed the medical records of all 43 patients who received implantable LVADs at the Mount Sinai Medical Center. After 1998, a number of protocol modifications were instituted. Vascular grafts were changed from a low-porosity, woven polyester (Cooley) to a gelatin-sealed, knitted polyester graft (Vascutek), the devices were implanted pre-peritoneally rather than in the posterior rectus sheath, and extensive drainage of the chest and pre-peritoneal pocket was used. The following anti-coagulation regimen was used: low-molecular-weight Dextran for 1 day, initiated after chest tube drainage <50 cc/hour; then IV heparin for 10 to 14 days, beginning at 500 U/hour, slowly increasing partial thromboplastin time to 1.5 to 2 x control; and finally Coumadin, maintaining the international normalized ratio at 2.5 to 3.5. Daily aspirin, 325 mg, was begun on post-operative Day 7. We compared 22 patients who electively underwent surgery before the changes, Group I, with 18 patients treated thereafter, Group II. RESULTS: Groups I and II were well matched with regard to age (47 vs 44 years); cause of heart failure (idiopathic, 50% vs 44%; ischemic, 50% vs 56%), and duration of support (79 vs 76 days). The incidence of thromboembolic cerebrovascular events was significantly less in Group II (6%) than in Group I (23%), p = 0.025. The incidence of bleeding increased mildly in Group I. Pocket infections occurred in 27% of Group I patients vs 11% of Group II patients, p = 0.018. Only 2 patients (11%) in Group II died while receiving device support, vs 7 (32%) in Group I, p = 0.019. CONCLUSIONS: Our results indicate that pre-peritoneal implantation, use of a new generation of vascular grafts, extensive drainage, and a more restricted anti-coagulation regimen improve outcome after Novacor LVAD implantation for advanced heart failure.