Hematopoietic cell transplantation (HCT) is an established and potentially curative therapeutic option for hematologic cancers. HCT survivors are at risk of developing long-term complications impacting on morbidity and mortality. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been anecdotally described after HCT. However, the incidence and clinical characteristics of patients with OH and POTS after HCT has not been well defined. This retrospective study included 132 patients who had HCT between March 2011 and July 2018 and were referred to Cardio-oncology clinic. Patients were screened for OH and POTS. Using logistic regression analysis we evaluated the association between clinical factors and the incidence of OH and POTS. Median age was 58 (47–63) years, 87 (66%) patients were male, 95 (72%) were Caucasian. OH was diagnosed in 30 (23%) subjects and POTS in 12 (9%) after the HCT. No significant differences in demographic characteristics were found when comparing patients with and without OH or POTS. The two groups did not differ for cardiovascular diseases prevalence nor for the prior use of antihypertensive drugs. Previous radiotherapy and treatment with specific chemotherapy drugs were found to be associated with the incidence of OH or POTS, but none of the factors maintained the significance in the multivariate model. Pharmacological therapy was required in 38 (91%) cases, including a b-adrenergic blocker (n = 24, 57%), midodrine (n = 24, 57%) and fludrocortisone (n = 7, 18%). Orthostatic intolerance syndromes are commonly diagnosed in patients referred to the cardiologist after HCT, involving approximately 1/3 of patients and requiring pharmacological therapy to cope with symptoms in the majority of cases. Risk factors specific to this population are identified but cannot fully explain the incidence of POTS and OH after HCT.

It was the dream of many cardiac surgeons in the mid-20th century to transplant a healthy heart into a patient dying of end-stage heart disease, but it was in the research laboratories of Dr Norman Shumway in the Stanford University Department of Surgery that he and his research fellow, Dr Richard Lower (Figure 1), perfected the surgical procedure and, importantly, demonstrated normal physiologic function by the resulting denervated heart, which could support normal activity in a canine model.

BACKGROUND:Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). METHODS:We studied 66 consecutive patients implanted with the TAH at our institution from 2006 through 2012 and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. RESULTS:Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared with those in profiles 2-4 (74% vs 95%, log rank: P = .015). For the 50 patients surviving to heart transplantation, the 1-year posttransplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile with less severe profiles (79% vs 84%; log rank test P = .7; hazard ratio [confidence interval] 1.3 [0.3-4.8]). CONCLUSIONS:Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to transplantation compared with less sick profiles. INTERMACS profile at the time of TAH implantation did not affect 1-year survival after heart transplantation.

Background. The changing epidemiology of cardiac allograft rejection has prompted many to question the yield of surveillance endomyocardial biopsy (EMB) in heart transplantation (HT) patients. We sought to determine the yield of EMB in the modern era. Methods. We evaluated 2597 EMBs in 182 consecutive HT patients who survived to their first EMB. The EMBs were categorized as asymptomatic or clinically driven and were compared based on era of antiproliferative therapy use at our center (early azathioprine era: 1990-2000 vs modern mycophenolate era: 2000-2011). Results. In the modern era, patients had a higher prevalence of risk factors for developing rejection (>= International Society of Heart and Lung Transplantation grade 2R); however, the frequency of rejection was decreased at all times (0-6months: 60.2% vs 21.5%, P < 0.001, 6-12 months: 26.8% vs 1.8%, P < 0.001, 12-36 months: 32.3% vs 10.5%, P = 0.006). The yield of asymptomatic EMB decreased in the modern era between 0 and 6 months (10.9% vs 3.12%), 6 to 12 months (17% vs 0%), and years 2 to 3 (6.1% vs 1.5%). In the early era, the odds ratio of rejection during asymptomatic EMB compared to a clinically driven EMB was 0.47 (95% confidence interval, 0.31-0.71) and was decreased in the modern era (0.17 [0.07-0.42], P = 0.04). The probability of detecting rejection on asymptomatic EMB was significantly reduced in the modern era, even after adjustment for tacrolimus and induction therapy (1% vs 8%, P < 0.001). Conclusions. The clinical yield of surveillance EMB has decreased in the modern era. The EMB in asymptomatic patients longer than 6 months after HT warrants further scrutiny.

Congestive heart failure represents a disease process of epidemic proportions in the United States, with 900,000 annual hospitalizations for New York Heart Association class III to IV symptoms. The inexorable deterioration of this group of patients has, until recently, been delayed by pharmacotherapy and by the use of automated implantable cardioverter defibrillators and cardiac resynchronization therapy. The authors propose that a major component of the downhill course of New York Heart Association class IV left heart failure is secondary to right heart failure and present the major predictors of right ventricular dysfunction. This, together with the limited availability of heart transplant donors, has led to the development of the left ventricular assist devices and the total artificial heart. Contrasting and comparing these devices have permitted insight into the importance of right ventricular function in the pathophysiology of heart failure, especially in the decision to proceed with left ventricular assist device placement, which is limited by right heart dysfunction or biventricular replacement with the total artificial heart.

1 study the third-generation beta-blocker, nebivolol, in a rat model of aldosterone/salt treatment – induced hypertensive heart disease and show that myocyte necrosis is incited by oxidative stress secondary to an increase in cytosolic free calcium and mitochondrial calcium overload — a process that overwhelms the endogenous zinc (Zn)-based antioxidants. Using the fi rst-generation beta-blocker atenolol as a control, treatment with nebivolol induced activation of endothelial nitric oxide synthase, nitric oxide (NO) generation, and a marked increase in intracellular Zn. Conversely, there was a concom-itant decrease in intracellular and subsarcolemmal mitochondrial calcium levels. Likewise, there was attenuation of mitochondrial hydrogen peroxide production and lipid peroxidation, inhibition of microscopic myocardial scarring, and a reduction in collagen volume fractions. They postulate an intriguing pathophysiologic phenomenon whereby nebivolol, acting as a b 3 agonist, increases NO formation leading to a rise in cytosolic free Zn. This inhibits intracellular and mitochondrial calcium overload, which ameliorates many of the detrimental effects of reactive oxygen species (ROS), lipid peroxidation, and the eventual myocardial scarring. Several important points can be gleaned from this study. First, this animal model of hypertensive cardiomyopathy serves as an effective model of sudden cardiac death as both myocardial fi brosis and adverse remodeling are key features of this disease process. This hypothesis, originally formulated by Weber and others, served as a fundamental basis for the RALES and EPHESUS trials. This concept was reviewed and con fi rmed by Esposito et al 2 in a canine model of pacing-induced systolic heart failure, interstitial fi brosis, and myocardial electrical activation delays. They showed that mineralocorticoid

LVAD implantation or heart transplantation.The solution proposed is the surgical implantation of a transapical LV vent (TLVV) through a minimally invasive approach.TLVV reduces significantly the pulmonary edema and it gives the chance to convert AV-ECMO circuit to a short-term LVAD as a bridge to solution.Methods and Materials: From January 2010 to June 2012, 16 patients supported by pheripheral AV ECMO for cardiogenic shock underwent TLVV implantation.Cannulation was done through a mini-torachotomy with the seldinger technique using an arterial high-flow cannula.TLVV was connected to the venous inflow line of the AV ECMO.The switch from AV ECMO to short term LVAD has been done in two stages: the weaning from the right circulatory support (intermediate stage: A-A ECMO) and the subsequent weaning from the oxygenator.Results: In-hospital mortality was 47,5 %.In 12 patients (75,0%) pulmonary function significantly improved.AV ECMO circuit was simplified to a short term LVAD in 10 patients.Ten pts were bridged to a definitive treatment: heart transplantation in 3 patients, permanent LVAD implantation in 2 patients and bridge to recovery in 5 patients.In hospital survival in patients arrived to these solutions was 8/10 (80,0%).Conclusions: TLVV improved pulmonary function and it gave the possibility to switch from the A-V ECMO to a short-term LVAD.After clinical stabilization of patients it was possible to access to a definitive treatment.We think that in the setting of an AV ECMO, TLVV implantation is useful in order to identify the best candidate for permanent LVAD, heart transplantation or recovery reducing significantly the risk of unsuccess.

The total artificial heart (TAH) orthotopically replaces a recipient's native ventricles and all four cardiac valves, interrupting neural and hormonal signaling pathways that are dependent upon the intact ventricular myocardium. B-type natriuretic peptide (BNP) is a cardiac neurohormone primarily secreted from ventricular cardiomyocytes in response to cardiac stretch. In healthy individuals, BNP decreases vascular tone, increases renal blood flow, promotes natriuresis and suppresses the renin–aldosterone axis.

The total artificial heart (TAH) orthotopically replaces the cardiac ventricles, interrupting neural and hormonal signaling pathways dependent upon the myocardium. We hypothesized that repletion of BNP after ventriculectomy would improve renal function and increase urine output.

BACKGROUND:The total artificial heart (TAH) replaces the heart with 2 pneumatic pumps and 4 tilting disk mechanical valves. It was hypothesized that patients receiving TAH support have persistent hemolysis that resolves after heart transplantation (HT). METHODS AND RESULTS:Hematocrit (HCT) was compared in patients on TAH to left ventricular assist device (LVAD) support for bridge to HT. Data were compared with t tests. The TAH (n = 36; mean age 47 ± 13 years) and LVAD patients (n = 14; mean age 53 ± 12 years) were supported for a median of 83 (interquartile range [IQR] 43-115) and 106 days (IQR 84-134), respectively. Hematocrit was similar between the TAH and LVAD patients (34 ± 6% vs 37 ± 5%; P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 ± 2% vs 24 ± 3%), 4 (22 ± 3% vs 26 ± 3%), 6 (22 ± 4% vs 30 ± 4%), and 8 weeks (23 ± 4% vs 33 ± 5%; P < .001 for all). There were no differences in HCT at 1 (30 ± 4% vs 29 ± 7%; P = .42) and 3 months (35 ± 7% vs 35 ± 4%; P = .98) after removal of the devices for HT. TAH patients had undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 ± 384 units/L), and detectable plasma free hemoglobin in 40% of measurements (21 ± 15 mg/dL). High sensitivity C-reactive protein (52 ± 50 mg/dL) was elevated, and reticulocyte production index was decreased (1.6 ± 0.6). CONCLUSIONS:Patients implanted with a TAH have persistent anemia that resolves only after HT. The association of hemolysis, ineffective erythropoiesis, and inflammation with the TAH warrants further study.

Pre Implant Noncompliance Does Not Predict Social Success in LVAD Recipients M. Maltby, M. Flattery, A. Barclay, V. Kasirajan, D. Tang, M. Hess, S. Harton, M.E. Olbrisch, K. Shah. Department of Social Work, Virginia Commonwealth University Health System, Richond, VA; Pauley Heart Center, Virginia Commonwealth University Health System, Richmond, VA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA.

Endomyocardial biopsy (bx) remains the preferred mode of cardiac allograft rejection surveillance. The frequency and morbidity of acute cellular rejection (ACR) has decreased with modern immunosuppression. We studied the yield of bx in the 1st year after heart transplantation (HT) to determine if traditional protocols are justified.

A 42-year-old diabetic man was admitted with systolic heart failure and pulmonary hypertension being treated with sildenafil for the previous year. With an increase in creatinine, he experienced 3 episodes of ventricular tachycardia and ventricular fibrillation. Withdrawal of the phosphodiesterase (PDE) inhibitor resulted in no further episodes of dysrhythmias. The basic pharmacology of PDE inhibitors is presented and the use of PDE-3 inhibitors for the treatment of heart failure causing an increase in sudden death is also reviewed. There have been several cases of sudden death associated with sildenafil use and with its increasing use in patients with severe pulmonary hypertension and decompensated heart failure. The authors also reviewed the electrophysiologic effects of PDE-5 inhibitors associated with their use. The crossover between PDE-3 and PDE-5 inhibitors is also discussed and caution is urged when contemplating the use of PDE-5 inhibitors in patients with systolic heart failure and pulmonary hypertension.

The CardioWest Total Artificial Heart (TAH) replaces the entire heart with two pneumatic pumps and four tilting disk mechanical valves and is an effective way to bridge dying patients to heart transplantation (HT). We hypothesized that patients with a TAH have anemia from pump-related hemolysis which improves after HT. We evaluated patients who received a TAH as a bridge to HT. Data were abstracted from the medical records. Thirty-six patients (age 47±13 years) were supported with a TAH for median of 83 days (IQR: 43,115). When compared to baseline, hematocrit (HCT) was decreased after TAH implantation at 2 weeks (34±6 g/dL vs 20±2 g/dL, p<0.001), 4 weeks (22±3 g/dL, p<0.001), 6 weeks (22±4 g/dL, p<0.001), and 8 weeks (23±4 g/dL, p<0.001). However, HCT increased significantly at 4 weeks after the device was removed for HT (23±4 g/dL vs 30±4 g/dL, p<0.001). Laboratory data obtained while on TAH support suggested ongoing hemolysis including an undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1128±384 units/L) in all samples, and elevated plasma free hemoglobin that was detectable in 40% of measurements (mean of 21±15 mg/dL in those with detectable levels). The mean reticulocyte production index value was decreased (1.6±0.6) indicating ineffective erythropoiesis. Inflammatory markers were elevated: high sensitivity c-reactive protein (52±50 mg/dL) was elevated in all cases and ferritin (745±703 ng/mL) was increased in 62% of evaluations. Patients implanted with the total artificial heart have persistent anemia that corrects after heart transplantation. Laboratory data suggests that in addition to hemolysis from the four mechanical heart valves, there is ineffective erythropoiesis and an increased inflammatory state.

BACKGROUND: The total artificial heart (TAH) consists of two implantable pneumatic pumps that replace the heart and operate at a fixed ejection rate and ejection pressure. We evaluated the blood pressure (BP) response to exercise and exercise performance in patients with a TAH compared to those with a with a continuous-flow left ventricular assist device (LVAD).METHODS: We conducted a single-center, retrospective study of 37 patients who received a TAH and 12 patients implanted with an LVAD. We measured the BP response during exercise, exercise duration and change in tolerated exercise workload over an 8-week period.RESULTS: In patients with a TAH, baseline BP was 120/69 +/- 13/13, exercise BP v. as 118/72 +/- 15/10 and post-exercise BP was 120/72 +/- 14/12. Mean arterial BP did not change with exercise in patients with a TAH (88 +/- 10 vs 88 +/- 11; p = 0.8), but increased in those with an LVAD (87 +/- 8 vs 95 +/- 13; p < 0.001). Although the mean arterial BP (MAP) was negatively correlated with metabolic equivalents (METs) achieved during exercise, the association was not statistically significant (beta = -0.1, p = 0.4). MAP correlated positively with METs achieved in patients with LVADs (MAP: beta = 0.26, p = 0.04). Despite the abnormal response to exercise, patients with a TAH participated in physical therapy (median: 5 days; interquartile range [IQR] 4 to 7 days) and treadmill exercise (19 days; IQR: 13 to 35 days) early after device implantation, with increased exercise intensity and duration over time.CONCLUSIONS: During circulatory support with a TAH, the BP response to exercise was blunted. However, aerobic exercise training early after device implantation was found to be safe and feasible in a supervised setting. J Heart Lung Transplant 2011;30:1207-13 (C) 2011 International Society for Heart and Lung Transplantation All rights reserved.

Purpose: The effect of B-type natriuretic peptide (BNP) on renal function in congestive heart failure is controversial. Total Artificial Heart (TAH) patients undergo ventriculectomy removing the major endogenous source of BNP. They represent a unique population to study the effect of BNP on renal function. We hypothesize that BNP withdrawal after TAH results in renal failure. Methods and Materials: We performed a retrospective analysis of 42 patients implanted with a TAH. Early in our experience, nesiritide (NES) was not used routinely. Glomerular filtration rate (GFR) before and 24 hrs after TAH implant was assessed. Based on these results, low dose NES was routinely used at TAH implant and then withdrawn following postop stabilization. GFR preceding NES withdrawal was compared to GFR 24 hrs after withdrawal. Results: 7 patients were not on NES at implant. 1 was transplanted 24 hrs following implant. 1 required hemodialysis (HD) immediately postop. In the remaining 5 patients, mean GFR decreased from 116 18.6 to 73.2 23.2 ml/min/1.73 m (p 0.15). 35 patients were on NES at implant. 2 were on HD and 1 was on pheresis at implant. 6 required HD immediately postop. 3 patients remained on nesiritide until transplant. The remaining 23 pts had NES withdrawn with a mean GFR decrease from 102.3 8.4 to 85.3 8.9 ml/min/1.73 m (p 0.001). Many patients required restarting NES. 16 patients were successfully weaned off NES. The response of GFR to NES in a representative patient is shown. Conclusions: Loss of BNP following ventriculectomy adversely affects GFR. Nesiritide and subsequent cautious withdrawal is an effective strategy to minimize renal dysfunction following TAH implant. This supports the notion that BNP has a role in renal homeostasis.

The total artificial heart (TAH) consists of two implantable pneumatic pumps operating at a fixed ejection rate and ejection pressure. Increases in cardiac output during activity with the TAH are thought to be dependent on increased venous return. The blood pressure (BP) response and safety of exercise in patients with a TAH have not been reported. We hypothesized that blood pressure augments in response to exercise in patients with a TAH.

The medical community has seen an explosive rise in the utilization of implantable mechanical circulatory support devices for late-stage cardiomyopathy. Care for these complex patients requires a basic understanding of device physiology and potential complications. This review focuses on an algorithm that incorporates a careful clinical history and examination with diagnostic modalities for the evaluation of a patient who is failing therapy with a continuous-flow left ventricular assist device, as well as the general management and optimization of patients implanted with an artificial heart.