Advanced Heart Failure: Therapeutic Options and Challenges in the Evolving Field of Left Ventricular Assist Devices.

Heart Failure is a chronic and progressively deteriorating syndrome that has reached epidemic proportions worldwide. Improved outcomes have been achieved with novel drugs and devices. However, the number of patients refractory to conventional medical therapy is growing. These advanced heart failure patients suffer from severe symptoms and frequent hospitalizations and have a dismal prognosis, with a significant socioeconomic burden in health care systems. Patients in this group may be eligible for advanced heart failure therapies, including heart transplantation and chronic mechanical circulatory support with left ventricular assist devices (LVADs). Heart transplantation remains the treatment of choice for eligible candidates, but the number of transplants worldwide has reached a plateau and is limited by the shortage of donor organs and prolonged wait times. Therefore, LVADs have emerged as an effective and durable form of therapy, and they are currently being used as a bridge to heart transplant, destination lifetime therapy, and cardiac recovery in selected patients. Although this field is evolving rapidly, LVADs are not free of complications, making appropriate patient selection and management by experienced centers imperative for successful therapy. Here, we review current LVAD technology, indications for durable MCS therapy, and strategies for timely referral to advanced heart failure centers before irreversible end-organ abnormalities.

Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters.

INTRODUCTION: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an inodilator that might be an effective agent in the treatment of PH and RVF. The aim of this study was to examine the impact of the duration of cardiopulmonary bypass (CPB) on the therapeutic drug monitoring of LS and to evaluate the effect of preemptive administration of LS on perioperative hemodynamic and echocardiographic parameters in cardiac surgical patients with preexisting PH. MATERIALS AND METHODS: In this study, LS was administered in adult patients undergoing cardiac surgery before CPB in order to prevent exacerbation of preexisting PH and subsequent right ventricular dysfunction. Thirty cardiac surgical patients with preoperatively confirmed PH were randomized to receive either 6 µg/kg or 12 µg/kg of LS after the induction of anesthesia. The plasma concentration of LS was measured after CPB. In this study, a low sample volume was used combined with a simple sample preparation protocol. The plasma sample was extracted by protein precipitation and evaporated; then, the analyte was reconstituted and detected using specific and sensitive bioanalytical liquid chromatography with mass spectrometry (LC-MS/MS) methodology. The clinical, hemodynamic, and echocardiographic parameters were registered and evaluated before and after the administration of the drug. RESULTS: A fast bioanalytical LC-MS/MS methodology (a run time of 5.5 min) was developed for the simultaneous determination of LS and OR-1896, its main metabolite in human plasma. The LC-MS/MS method was linear over a range of 0.1-50 ng/mL for LS and 1-50 ng/mL for its metabolite OR-1896. Measured plasma concentrations of LS were inversely related to the duration of CPB. LS administration before CPB during cardiac surgery was effective in reducing pulmonary artery pressure and improving hemodynamic parameters after CPB, with a more pronounced and durable effect of the drug at the dose of 12 µg/kg. Additionally, administration of LS at a dose of 12 µg/kg in cardiac surgical patients with PH before CPB improved right ventricular function. CONCLUSION: LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery.

Anomalous circumflex artery: a benign variant generating a malignant potential after valve surgery.

Coronary artery anomalies are a diverse group of congenital disorders presenting with highly variable clinical manifestations. The anomalous origin of left circumflex artery from the right coronary sinus following a retro-aortic trajectory is a well-recognized anatomic variation. Despite its benign course, it can prove lethal in association with valvular surgery. When single aortic valve replacement or combined with mitral valve replacement is performed, the aberrant coronary vessel may be compressed by or between the prosthetic rings triggering postoperative lateral myocardial ischemia. If left untreated, the patient is at risk of sudden death or myocardial infarction with its detrimental complications. Skeletonization and mobilization of the aberrant coronary artery is the most widely accepted intervention, but valve downsizing or concomitant surgical or transcatheter revascularization have also been described. However, large series are lacking from the literature. Therefore, no guidelines exist. This study is a thorough review of the literature concerning the aforementioned anomaly in association with valvular surgery.

Intraoperative mydriasis in left ventricular assist device patients. Do eyes never lie?

We report two cases of transient intraoperative mydriasis in left ventricular assist device (LVAD) patients with no profound underlining neurological pathology. Both cases concern females on LVAD for more than 30 months, due to dilated cardiomyopathy, as a bridge to transplant. A possible pathophysiology mechanism is suggested. As LVAD patients' life expectancy increases, more and more physiological alterations due to laminar flow will be revealed and must be taken into consideration for the better care of this patient group.

Prospective Phenotyping of Right Ventricle Function Following Intra-Aortic Balloon Pump Counterpulsation in Left Ventricular Assist Device Candidates: Outcomes and Predictors of Response.

Intra-aortic balloon pump (IABP) may be applied to optimize advanced heart failure (AHF) patients and improve right ventricular (RV) function before left ventricular assist device (LVAD) implantation. We aimed to evaluate the outcome of this intervention and define RV response predictors. Decompensated AHF patients, not eligible for LVAD because of poor RV function, who required IABP for stabilization were enrolled. Echocardiography and invasive hemodynamics were serially applied to determine fulfillment of prespecified "LVAD eligibility RV function" criteria (right atrium pressure [RA] <12 mm Hg, pulmonary artery pulsatility index [PAPi] >2.00, RA/pulmonary capillary wedge pressure [PCWP] <0.67, RV strain <-14.0%). Right ventricular-free wall tissue was harvested to assess interstitial fibrosis. Eighteen patients (12 male), aged 38 ± 14 years were supported with IABP for 55 ± 51 (3-180) days. In 11 (61.1%), RV improved and fulfilled the prespecified criteria, while seven (38.9%) showed no substantial improvement. Histopathology revealed an inverse correlation between RV interstitial fibrosis and functional benefit following IABP: interstitial fibrosis correlated with post-IABP RA ( r = 0.63, p = 0.037), RA/PCWP ( r = 0.87, p = 0.001), PAPi ( r = -0.83, p = 0.003). Conclusively, IABP improves RV function in certain AHF patients facilitating successful LVAD implantation. Right ventricular interstitial fibrosis quantification may be applied to predict response and guide preoperative patient selection and optimization. http://links.lww.com/ASAIO/A995.

The effect of paracorporeal pulsatile biventricular assist devices on allosensitization in adults: A comparison with left ventricular assist devices.

Ventricular assist devices (VADs) have been associated with the development of anti-HLA antibodies ('allosensitization'), but data on devices providing biventricular support in adults are limited. We sought to characterize differences in anti-HLA antibody formation in adult patients receiving left- (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT) by retrospectively reviewing the records of adult patients who have undergone VAD implantation at our institution. We assessed 82 patients supported with a pulsatile-flow paracorporeal BiVAD and compared them with 40 patients receiving LVAD till 2018. Forty-eight (58.5%) of the BiVAD and 23 (57.5%) of the LVAD patients were eventually transplanted (p = 0.91) with an average time to transplantation 559 and 598 days, respectively (p = 0.73). Evidence of sensitization pre-VAD was found in 11.0% of the BiVAD patients and 15.0% of the LVAD ones (p = 0.53); these percentages rose to 43.9% (p < 0.001) and 40.0% (p = 0.01), respectively. The post-VAD sensitization status was not significantly different between the BiVAD and the LVAD group (p = 0.68). De novo sensitization was comparable between the two groups (p = 0.55). Post-transplantation outcomes regarding rejections and cardiac allograft vasculopathy were also similar. Conclusively, BiVAD- and LVAD- induced allosensitization do not appear to differ significantly.

A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension.

During cardiac operations, weaning from cardiopulmonary bypass (CPB) may prove challenging as a result of superimposed acute right ventricular dysfunction in the setting of elevated pulmonary vascular resistance (PVR). The aim of this study was to retrospectively evaluate the effect of inhaled milrinone versus inhaled iloprost in patients with persistent pulmonary hypertension following discontinuation of CPB. Eighteen patients with elevated PVR post-bypass were administered inhaled milrinone at a cumulative dose of 50 µg kg-1. These patients were retrospectively matched with 18 patients who were administered 20 µg of inhaled iloprost. Both drugs were administered through a disposable aerosol-generating jet nebulizer device and inhaled for a 15-min period. Hemodynamic measurements were performed before and after cessation of the inhalation period. Both inhaled milrinone and inhaled iloprost induced significant reductions in mean pulmonary artery pressure and PVR and significant increases in cardiac index in patients with post-CPB pulmonary hypertension. The favorable effect of both agents on the pulmonary vasculature was confirmed by echocardiographic measurements. Both agents were devoid of systemic side effects, since mean arterial pressure and systemic vascular resistance were not affected. A decrease in intrapulmonary shunt by inhalation of both agents was also demonstrated. Pulmonary vasodilatation attributed to iloprost seems to be of greater magnitude and of longer duration as compared to that of inhaled milrinone. Both substances proved to be selective pulmonary vasodilators. The greater magnitude and of longer duration vasodilatation attributed to iloprost may be due to its longer duration of action.

Cardiac transplantation: towards a new noninvasive approach of cardiac allograft rejection.

INTRODUCTION: Cardiac allograft rejection (CAR) may occur after transplantation and remains silent, until hemodynamic deterioration takes place. Endomyocardial biopsy (EMB) is applied to early detect CAR. Although, flexible bioptoms have decreased the incidence of lethal complications, EMB remains an invasive procedure carrying risk of tamponade and permanent heart block. Therefore, a new non-invasive approach is needed. Areas covered: AlloMap molecular expression testing and graft-derived cell-free DNA (GcfDNA) test can be used as blood indices of acute and chronic CAR, respectively. Among diagnostic techniques, only echocardiography and cardiovascular magnetic resonance (CMR) have shown a strong correlation with EMB. Echocardiography is bedside, cost and time saving. However, the currently used indices are insensitive markers of CAR. Global longitudinal strain (GLS) can diagnose the subclinical CAR and be used together with EMB to monitor acute CAR. CMR can improve our diagnostic accuracy using T2STIR, T1, T2 mapping, early/late gadolinium enhancement and functional assessment. Expert commentary: A new non-invasive approach in asymptomatic transplanted patients should be based on a serial assessment of AlloMap, GcfDNA testing, echocardiographic and CMR indices that will guide the indication for EMB. In symptomatic patients immediate EMB is the approach of choice, since they have high likelihood for CAR.

Percutaneous transcatheter closure of aorto-right ventricular fistula using the Amplatzer duct occluder.

The occurrence of aorto-right ventricular fistula after an aortic valve replacement is rare. If it remains untreated, this condition can result in heart failure and could thus significantly compromise patient survival. Surgical closure is the treatment of choice; however, transcatheter closure has been attempted with relatively acceptable results. Here, we report on a patient who presented with heart failure with an aorto-right ventricular fistula that was present for nine years following aortic valve replacement. Successful transcatheter closure of the fistula with the use of the Amplatzer duct occluder was performed, suggesting that the percutaneous approach is an efficient technique for the treatment of such fistulae.

Left ventricular geometry and systolic function improvement after percutaneous closure of aortic prosthetic paravalvular leak.

Paravalvular leak (PVL) represents a potential complication of valve replacement surgery. The 'gold standard' treatment for patients with severe prosthetic dysfunction, hemolysis or symptoms, is surgery. Reoperative valve surgery for such patients is related to high morbidity and mortality rate. The percutaneous closure of PVL is feasible and safe, when performed at experienced interventional cardiologic centers. Herein, the case is reported of a patient who showed a significant improvement in left ventricular systolic function after transcatheter closure of an aortic prosthetic PVL with an Amplatzer duct occluder II (ADO II). A review of the current literature is also provided.

Successful epoprostenol withdrawal in pulmonary arterial hypertension: case report and literature review.

Pulmonary arterial hypertension is a rare and devastating disease characterized by vascular proliferation and remodeling. Epoprostenol, the drug counterpart of the eicosanoid prostacyclin, produced by the vascular endothelial cells, is the drug of choice for this disease. Its capacity to act rapidly and to significantly improve survival prospects in severe pulmonary hypertension patients has been supported by a wealth of evidence. Intravenous epoprostenol was believed to require therapy of indefinite duration. Since 2001, oral drugs have been approved for specific treatment. The availability of newer and less invasive drug therapies for pulmonary arterial hypertension led physicians to withdraw epoprostenol in carefully selected patients. We report a case of successful intravenous epoprostenol interruption in a patient with idiopathic disease. A literature review on epoprostenol withdrawal in pulmonary hypertension in adult patients is also provided.

Thrombosis of the ascending aorta during mechanical circulatory support in a patient with cardiogenic shock.

Cardiogenic shock after percutaneous coronary intervention (PCI) is a life-threatening complication and is most often related to abrupt vessel closure. We present the case of a patient who developed cardiogenic shock after PCI and was supported with intra-aortic balloon counterpulsation and the Levitronix CentriMag short-term mechanical circulatory support. He was evaluated for implantation of a ventricular assist device as bridge-to-transplantation. Preoperative transesophageal echocardiography revealed a massive thrombus of the aortic root and ascending aorta despite optimal anticoagulation regimen. The patient succumbed due to multiorgan failure.

Intracoronary infusion of selected autologous bone marrow stem cells improves longitudinal myocardial strain and strain rate in patients with old anterior myocardial infarction without recent revascularization.

AIMS: We sought to evaluate the efficacy of intracoronary infusion of selected bone marrow stem cells (BMSCs) in patients with remote, anterior non-viable MI by the use of tissue Doppler imaging. METHODS AND RESULTS: We infused selected CD133+ and CD133-CD34+ BMSCs in 10 patients enrolled in the study. Peak systolic strain rate, maximum strain during the cardiac cycle (epsilon(max)), strain during ejection time (epsilon(et)), and post-systolic strain (epsilon(ps)) were measured. Peak systolic strain rate (-0.69 +/- 0.2 vs. -1.15 +/- 0.27, P = 0.001), epsilon(max) (-9.87 +/- 3.30 vs. -15.57 +/- 5, P = 0.006), and epsilon(et) (-7.45+/-2.86 vs. -10.92 +/- 4.45, P = 0.015) improved significantly during the rest study 6 months after cell infusion. Low-dose inotropic challenge also showed significant improvement of longitudinal deformation indices in the follow-up study. Global ejection fraction did not improve significantly after cell therapy. CONCLUSION: Intracoronary infusion of selected BMSCs in patients with remote, anterior, non-viable myocardial infarction is safe and leads to improvement of longitudinal deformation indices 6 months after the infusion.

Increased number of circulating progenitor cells after implantation of ventricular assist devices.

BACKGROUND: Bone marrow-derived circulating progenitor cells possess tissue repair potential, improving perfusion, left ventricular remodeling, and contractility in experimental models. We quantified and investigated the kinetics of 4 circulating progenitor cell sub-populations on the basis of CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antigen expression. METHODS: CD34+, CD34+/CD133+/VEGFR-2-, CD34+/CD133+/VEGFR-2+, and CD34+/CD133-/VEGFR-2+ cells were counted in 10 male patients with end-stage congestive heart failure. Five underwent left ventricular/biventricular assist device (LVAD/BiVAD) implantation (VAD group), and 5 were ineligible for VAD implantation (no-VAD group). Peripheral blood was collected at 3 time points for each patient: before, 15, and 60 days after VAD placement in the VAD group and at the same time points in the no-VAD group. Purified CD34+ cells were stained with anti-CD34, anti-CD133, and anti-VEGFR-2 monoclonal antibodies and analyzed by flow cytometry. Serum levels of granulocyte-colony stimulating factor (G-CSF), interleukin-8, vascular endothelial growth factor-alpha (VEGF-alpha), and B-type natriuretic peptide (BNP) were also measured. RESULTS: In the VAD group the number of CD34+ cells/ml of blood tended to increase, from 159.6 +/- 137.0 at baseline to 428.9 +/- 224.3 at 15 days, and decreased to 343.8 +/- 165.7 at 60 days (p = 0.05 vs no-VAD group). In the other 3 cell populations, no significant differences occurred over time or between groups. A significant interaction between BNP levels and VAD status was observed (p = 0.005): BNP levels decreased over time in VAD patients vs no-VAD patients. G-CSF levels tended to decrease over time in both groups, but without a significant difference (p = 0.3). Serum levels of interleukin-8 and VEGF-alpha over time or between VAD and no-VAD patients were not significantly different. CONCLUSIONS: After VAD implantation, a transient increase occurs in the number of circulating CD34+ cells, in parallel to a reduction in BNP levels. Release of these cells from the bone marrow may contribute to the improvement of tissue perfusion and cardiac recovery occasionally seen after VAD placement.