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The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures.

Left ventricular assist devices (LVADs) are widely used in selected patients suffering from end-stage heart failure (HF). However, their large-scale use has been limited in the past by their adverse events rate. With the development of the third LVAD generation characterized by centrifugal pumps, the role and application of LVADs for treating HF patients has globally increased with improving results, better quality of life and survival. This led to a growing need for scientific evidence supporting the large-scale application of this therapy.

Background: Left ventricular assist devices (LVAD) are increasingly used in patients with end stage heart failure. The HeartAssist 5 and aVAD LVADs offer telemetric monitoring capabilities. Here we report our initial single centre experience with the largest telemonitoring cohort of LVAD patients. Methods: Eleven patients (9 males) received a telemonitoring-capable LVAD and were included in our telemonitoring cohort. Waveforms and alarm data were obtained from the telemonitoring system and hospital records were reviewed for clinical data. Results: Mean age at LVAD implantation was 59±5.1 years (mean ± standard deviation). Seven patients had non-ischemic cardiomyopathy and 4 patients had ischemic cardiomyopathy. Median LVEF at implant was 16% (IQR, 15–20%). The total follow-up time was 2,438 patient-days. A total of 6,216 alarm messages were generated in 11 patients. Most common were low flow alarms due to hypovolemia, followed by low flow alarms because of suspected pump thrombosis. One patient died during follow-up, one received a cardiac transplant and one had the LVAD explanted because of pump thrombosis. Pump thrombosis was suspected in 5 patients with 8 episodes of sudden flow decreases and laboratory signs of haemolysis. Conclusions: Real-time telemonitoring of LVAD pump flow, motor speed and power consumption is a promising tool in the follow-up of LVAD recipients. Trending pump flow over hours or days can assist in the early detection of complications, especially flow reductions due to hypovolemia and LVAD thrombosis. Further studies are warranted to delineate the impact of remote monitoring on patients’ prognosis.

The use of lateral thoracotomy (LT) for implanting left ventricular assist devices (LVADs) is worldwide increasing, although the available evidence for its positive effects compared with conventional sternotomy (CS) is limited. This systematic review and meta-analysis analyzes the outcomes of LT compared with CS in patients undergoing implantation of a centrifugal continuous-flow LVAD. Four databases and 1,053 publications were screened until December 2019. Articles including patients undergoing implantation of a centrifugal continuous-flow LVAD through LT were included. A meta-analysis to compare LT and CS was performed to summarize evidences from studies including both LT and CS patients extracted from the same population. Primary outcome measure was in-hospital or 30-day mortality. Eight studies reporting on 730 patients undergoing LVAD implantation through LT (n = 242) or CS (n = 488) were included in the meta-analysis. Left thoracotomy showed lower in-hospital/30-day mortality (odds ratio [OR]: 0.520, 95% confidence interval [CI]: 0.27-0.99, p = 0.050), shorter intensive care unit (ICU) stay (mean difference [MD]: 3.29, CI: 1.76-4.82, p < 0.001), lower incidence of severe right heart failure (OR: 0.41; CI: 0.19-0.87, p = 0.020) and postoperative right ventricular assist device (RVAD) implantation (OR: 0.27, CI: 0.10-0.76, p = 0.010), fewer perioperative transfusions (MD: 0.75, CI: 0.36-1.14, p < 0.001), and lower incidence of renal failure (OR: 0.45, CI: 0.20-1.01, p = 0.050) and device-related infections (OR: 0.45, CI: 0.20-1.01, p = 0.050), respectively. This meta-analysis demonstrates that implantation of a centrifugal continuous-flow LVAD system via LT benefits from higher short-term survival, less right heart failure, lower postoperative RVAD need, shorter ICU stay, less transfusions, lower risk of device-related infections and kidney failure. Prospective studies are needed for further proof.

Introduction: Pump thrombosis of left ventricular assist devices remains a devastating complication with high morbidity and mortality. Despite the improvements made, the matter affects many patients and the treatment options are limited to thrombolysis and surgical replacement. An alternative approach using the aspiration Indigo catheter was tested. Methods: An Indigo thrombectomy catheter was used within an in vitro model to assess the direct aspiration of prefabricated clots from three different positions within the HeartWare HVAD (inlet, outlet, and housing). The experiments were conducted with a straight and an angled catheter. The aspiration pressure was constant. The flow, power consumption, and pressure head of the left ventricular assist devices were measured at pre-defined measuring points. Results: The device was more effective (success rate 71%) at inlet and outlet of the left ventricular assist device. In addition, the duration of aspiration and the aspiration volume were shorter in comparison to the aspiration in the housing (inlet M = 19.75 s, outlet M = 60.50 s, and housing M = 38.75 s). Moreover, the aspiration volume was associated with the aspiration duration and the weight of thrombi but not with their volume. Noteworthy, the angled catheter showed an improved performance compared to the straight one (67%–33%). The recorded parameters showed no major changes during the use of the catheter. After application of the Indigo catheter, flow and pressure head of the pump could be restored. Conclusions: The aspiration system showed promising results under specific conditions for the treatment of pump thrombosis in an in vitro model. However, further examination, including in vivo experiments, will justify its effectiveness.

Chronic end-stage heart failure (CHF) is a major healthcare problem with rapidly growing incidences in Europe and the United States (1). With decreasing cardiac transplant rates worldwide, alternative treatment methods become increasingly important.

Background: Device thrombosis is one of the main complications in left ventricular assist devices (LVAD) therapy and remains a challenging issue. Data on device thrombosis management, especially on the application of direct thrombin inhibitors such as argatroban, is limited and a consensus on thrombosis management has not yet been established. Methods: In this study we analysed retrospective clinical data obtained from 26 patients on VAD therapy who received argatroban for suspected VAD thrombosis, between April, 2012 and February, 2017. Results: Thirteen patients (50%) showed resolution of thrombus after argatroban therapy. Eight of 26 patients (30.8%) were free of thrombotic events 90 days after discharge. Argatroban therapy was unsuccessful in 13 patients of the study cohort, leading to subsequent VAD-exchange. Six of 13 patients with first VAD-exchange had no thrombotic events 90 days after discharge. Six patients (23.1%) suffered from bleeding, especially gastrointestinal bleeding. No hemorrhagic strokes were observed. Three patients (11.5%) did not survive the follow-up period. Conclusions: Argatroban appears to be an alternative to other pharmacological treatment options in VAD thrombosis. Efficacy and safety characteristics are acceptable, but further investigation on larger populations is necessary.

In this article, we present the case of a 72-year-old male patient suffering from a severe form of singular isolated end-stage right heart failure based on arrhythmogenic right ventricular cardiomyopathy (ARVC), who was admitted to our clinic for acute cardiac decompensation.

Introduction: Heart failure (HF) is one of the rising problems in the contemporary society with growing incidences of end-stage HF. While heart transplantation (HT) is the gold standard treatment for end-stage HF, its availability is limited by the lack of heart donors. As a consequence, left ventricular assist devices (LVADs) are becoming key therapies as bridge to transplant (BTT) strategy to improve survival and outcomes.Areas covered: A significant advancement for wider applications of LVADs as BTT was facilitated by the introduction of miniaturized pumps such as the HVAD (HeartWare®, Medtronic, MN, USA), allowing intrapericardial implants and less-invasive approaches. In this review article, we describe the technical features of the HVAD and its outcomes in terms of efficacy and safety when implanted as BTT strategy. Moreover, we discuss the postoperative results of HT in HVAD recipients and its application in the pediatric population.Expert opinion: It has been demonstrated that the HVAD positively influences the survival of end-stage HF patients awaiting HT, with an acceptable rate of adverse events. Due to its reduced size, it is particularly suitable for LVAD implantations through lateral thoracotomy and in patients with small thoracic dimensions.

In June 2014 the worldwide first implantation of a new and promising Left Ventricular Assist System (LVAS) for end-stage heart failure therapy was performed by Dr. Schmitto and his team at Hannover Medical School, Hannover, Germany (1).

Purpose Despite maximal medican and surgical therapy, the outcomes of severe biventricular failure remain poor with mortality rates of up to 100%. The only definite therapy option for this disease is the total replacement of the heart - either by cardiac transplantation or by total artificial heart (TAH) implantation. Due to the lack of donor organs, mechanical assist devices are the most relevant option for these patients. The permanent availability of mechanical devices is especially attractive in emergency cases as well as in high-risk patients. The placement of two HeartMate 3 in the setting of a TAH is an alternative approach to pulsatile TAH implantation. We now present the worldwide first series of outcomes of this novel procedure. Methods We performed a retrospective analysis of seven consecutive patients who underwent off-label HeartMate 3 TAH implantation after cardiectomy at two international medical institions. Data was acquired using the in-house clinical databases. Follow-up time was thirty days postoperatively. Among perioperative baseline characteristics, adverse events and survival data were collected and analyzed. The retrospective study was approved by the loca institutional ethics committee. Results Out of 7 patients 4 were male (57%). Primary diagnosis was dilated cardiomyopathy in four cases (4/7, 57%) Other diagnoses were stone heart syndrome, restrictive cardiomyopathy and post-partum cardiomyopathy. All patients were previously supported by ECMO. 3 patients suffered from severe ventricular thrombosis. Intraoperative mortality was 0%. One patient was successfully transplanted after 71 days on device. One patient is still on-going on the device, currently discharged and waiting for heart transplantation (POD 259). Full mobility was achieved in both patients. In all cases postoperative hemodynamic stability was successfully achieved. No device related technical complications occured. Four patients died within thirty days of support (51%; POD 10-21). Causes of death were sepsis and multi-organ failure (3/4) and stroke (1/4). Conclusion It has been proven that the implantation of two HeartMate 3 VADs in the settings of a total artificial heart is a feasible concept with no technical adverse events in our patient population. In this high risk patient cohort, a reduction of 30-day-mortality from 100% to 57% was achieved.

Left ventricular assist devices (LVADs) are emerging as the treatment of choice for advanced heart failure due to the dearth of healthy donor hearts for cardiac transplantation. The HeartMate 3 LVAD is a novel centrifugal pump which was developed to provide hemodynamic support in heart failure patients, either as a bridge to transplant (BTT), myocardial recovery, or as destination therapy (DT). Technological and clinical advancements have led to optimized hemocompatibility and development of less invasive surgical procedures for the implantation of this pump. The worldwide first implantation of the HeartMate 3 was performed by Prof. Schmitto and his team at Hannover Medical School, Germany in 2014, paving the way for subsequent surgical developments. This article summarizes the advanced technological and clinical aspects of the HeartMate 3 and outlines future technical developments for safe and effective treatment of advanced heart failure.

Although rare, recovery of cardiac function after mechanical support of the left ventricle is the most desirable therapeutic goal in the treatment of end-stage heart failure.Herein, we present a novel implantable device for explantation of the HeartMate 3™ left ventricular assist device (LVAD) in patients, following cardiac recovery, avoiding (re-) sternotomy.This article demonstrates the feasibility of applying this novel device, which fits into the sewing ring of the LVAD.This custom-made mechanical plug offers a promising alternative to standard device-explantation procedures.

Background End-stage heart failure is associated with severe after-effects such as heart valve insufficiency, cardiac arrhythmias or end-organ dysfunctions. Renal failure or 'cardiorenal syndrome' is a critical end-organ disorder associated with advanced heart failure, which occurs due to low-output failure. Drug therapy or surgical interventions involving left ventricular assist device (LVAD) implantation may impede the progress of heart insufficiency and its after-effects including renal failure. In this study, we investigated the impact of a minimally invasive ventricular assist device implantation through upper hemisternotomy combined with anterolateral thoracotomy on renal function, in patients with perioperative renal failure. Methods We analyzed data obtained from 103 patients (80 males, 23 females; mean age 53.8±11.7) who underwent LVAD implantation at our clinic within a 15-year interval (2001-2016) and were dialyzed due to renal dysfunction. 90 patients were operated with the conventional LVAD implantation technique (standard approach surgery, SAS) and 13 underwent less invasive approach implantation (less invasive surgery, LIS). Results For all patients, data analysis showed significant increase of glomerular filtration rate (GFR) (44.2±56.48 mL/min; 95% CI: 33.81-55.28; P

Background: Functional mitral valve regurgitation is a frequent consequence of left ventricular dysfunction in patients with severe heart failure and is associated with a poor prognosis. It is hypothesized that in this patient group the mitral valve repair, respectively replacement, improves hemodynamics and clinical symptoms. As operative interventions with the help of heart-lung-machine are high risk procedures in these cases, the transcatheter mitral repair with MitraClip ® (Abbott Vascular, IL, USA) has recently become frequently used. Most of these cases experience a progress in left ventricular dysfunction, which finally leads to in an implantation of a left ventricular assist device. In this report, we describe a series of six cases in which patients with end stage heart failure and consecutive functional mitral valve regurgitation were supported with a left ventricular assist device after MitraClip implantation. We aimed to investigate, whether the MitraClip implantation leads to an improvement of the hemodynamic prior left ventricular assist device (LVAD)-implantation. Methods: We retrospectively analyzed the data of 6 patients (5 males, 1 female) with severe heart failure, who underwent LVAD implantation after the MitraClip procedure. The mean age at MitraClip procedure was 64.6 years, mean age at time of LVAD implantation was 65.5 years. The parameters examined were cardiac index (CI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and the pulmonary capillary wedge pressure (PCWP). Results: All patients had functional mitral regurgitation (MR). Severity of MR was reduced successfully in all treated patients. All patients were discharged with MR I-II and NYHA functional class III or IV after MitraClip procedure. The mean CI was 2.93 before MitraClip procedure and 2.36 before LVAD-Implantation. Mean LVEDD was 71 mm before MitraClip, mean LVEDD was 70.6 mm before LVAD, and 63.2mm after LVAD implantation respectively. The mean PCWP was 21.5 mmHg before MitraClip and 19.8 mmHg before LVAD implantation respectively. The mean left ventricular ejection fraction (LVEF) was 19.2% before MitraClip, the mean LVEF was 17.6% before LVAD and 15 % after LVAD implantation. Two of the LVAD implanted patients died due to post-operative complications. There were no complications after MitraClip procedure. Conclusions: Our presented patient cohort presented little hemodynamic improvement after the MitraClip procedure. There was no clinical benefit for the patients after MitraClip procedure, progressing left ventricular dysfunction could not be prevented and resulted in subsequent LVAD implantation.

Background: Driveline infection (DLI) is one of the leading causes for unplanned re-admissions of patients undergoing therapy with left ventricular assist devices (LVAD). In previous studies our group was able to show that a double tunneling implantation technique could significantly reduce infection rates one year after implantation. We now report the results of the five-year-follow up of patients receiving the double tunneling technique. Methods: We retrospectively analyzed patients receiving LVAD therapy with the HeartWare ventricular assist device (HVAD) (Medtronic, Minnesota, MN, USA) LVAD. For 36 patients (group 1) the driveline was tunneled via a conventional technique. In the remaining 33 patients (group 2) the drivelines were implanted by means of a double tunneling technique. The double tunnel driveline technique involved placement of the driveline in the sheath of the rectus muscle in the umbilical direction and then subcutaneously to the left (alternatively right) upper quadrant. We retrospectively compared both groups. Primary outcome parameters were infection rate and mortality. Results: Five years after LVAD implantation the DLI rate of patients operated by a double tunneling technique was significantly lower than in the conventional technique group [61% (n=22) group 1 vs . 30% (n=10) group 2, P=0.004]. The 5-year mortality was lower in group 2 [42% (n=15) group 1 vs . 27% (n=9) group 2] but did not achieve statistical significance (P=0.10). The days of LVAD support between the two groups were comparable (1,275.56±885.89 group 1 vs . 1,321.94±711.37 group 2). The tunnel technique itself showed to be strongly associated with the occurrence of DLI. Other elevated variables are liver disease and dilated cardiomyopathy as primary disease. Conclusions: Double tunneling technique for driveline implantation leads to significantly lowered infection rates after 5 years of LVAD therapy and it is associated with a lower mortality.

Background: Pump thrombosis is the most severe and acute complication of left ventricular assist device (LVAD) therapy and treatment remains challenging. Whilst lysis therapy is often not successful, the exchange of the occluded LVAD is currently the most applied therapeutic treatment for this event. With this study we examine the effects of minimal-invasive LVAD exchange on the rate re-thrombosis and outcomes as well as adverse events in the study group. Methods: Between February 2004 and December 2015 more than 600 LVADs were implanted at our institution. We retrospectively studied a patient cohort of 41 patients who underwent LVAD exchange because of pump thrombosis at a single institution. Outcomes, rates of re-thrombosis and adverse events were analyzed. Results: Between February 2004 and December 2015, 87 exchanges of LVADs were performed at a single center. In 41 cases pump thrombosis was the reason for LVAD exchange. A total of 28 patient years (10,276 days) were analyzed. Average ICU stay was 15.8±20.4 days and average in-hospital stay 38.1±37.3 days after LVAD exchange. After thirty days the survival rate was 80.5%, 75.6% after 6 months and 70.7% one year after LVAD exchange. Out of the study cohort, three patients have successfully undergone heart transplantation. Twelve patients suffered a stroke postoperatively (29%). Twelve patients needed postoperative dialysis (29%). No technical complications of the VAD were recorded in the study group. Two patients underwent successful LVAD explantation due to myocardial recovery. One year after LVAD exchange, 14 patients underwent re-exchange due to pump thrombosis (34%). Eight patients suffered from a LVAD related infection out of which two patients were treated by pump exchange. A total of 12 patients died during the complete one year follow up of this study (29%). Four patients died in the second, two in the third and one in the fourth year after LVAD exchange. The remaining 17 patients are still ongoing on the device. Conclusions: It is generally feasible to treat pump thrombosis via LVAD exchange. Yet, the exchange procedure is not without risk and the risk of re-thrombosis (34%), stroke (29%), postoperative dialysis (29%) and perioperative complications remains high.

Growing worldwide incidences of end-stage heart failure and declining rates of cardiac transplants have given rise to the need for alternative treatment options, based on mechanical circulatory support (MCS) devices such as left ventricular assist devices (LVADs). Technologically advanced LVADs such as the HVAD® (HeartWare®, Medtronic) facilitate safe and efficient treatment of heart failure patients with reduced post-operative complications, which is attributed to their considerably miniaturized size. This also facilitates the development and implementation of novel, minimally-invasive surgical techniques. The HVAD is a centrifugal pump, manufactured by HeartWare Inc., (Framingham, MA, USA) and subsequently by Medtronic Inc., (Minnesota, MN, USA), and has been approved for clinical application after receiving the CE Mark approval in 2008 and the FDA approval in 2012. Current research efforts are focused on further miniaturization alongside optimization of electronic and software controllers as well as implementation of the transcutaneous energy transfer (TET) technology. Salient features of the HVAD pump technology, clinical applications and future optimization strategies have been discussed in this article.

Background: Left ventricular assist device (LVAD) (HVAD, Medtronic, Minneapolis, MN, USA) implantation is already a widely accepted treatment option for end-stage heart failure (HF) but also still considered as a rescue therapy for patients suffering from cardiogenic shock. Standard LVAD implantation techniques are often associated with high mortality rates and can result in severe complications, like bleeding or right heart failure (RHF). The aim of our study was to assess the outcome of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 patients (so called “crash and burn” patients) undergoing a LVAD implantation by standard or less invasive surgery. Methods: We performed a retrospective evaluation of the 1-year outcome of 32 consecutive HF patients in cardiogenic shock, who underwent LVAD implantation in our institution. A total of 32 INTERMACS 1 patients were emergently operated. Fourteen patients (group A) were operated by using the “Hannover-VAD-technique”, which is widely known to be less invasive (upper hemisternotomy and a left-sided anterolateral thoracotomy). In contrast, 18 patients (group B) were implanted with LVAD by using the standard technique (full sternotomy). The primary endpoint was survival after 1 year without device-related re-operations. Secondary endpoints included combined analyses of rates of RHF, respiratory failure and bleeding during the trial period. Results: Baseline characteristics were similar in both groups. Survival after 1 year was higher in group A (69.7% vs. 50.0%). Technique-related adverse events (AEs) were also lower in the minimally invasive group, including a lower RHF (35.7% vs. 61.1%) and of further postoperative bleeding requiring surgery (14.3% vs. 33.3%). Conclusions: LVAD surgery in INTERMACS 1 patients is associated with remarkably good outcome considering the already very high mortality of those patients, and compared to previously reported surgical outcomes. Our study indicates that minimally invasive LVAD implantation in cardiogenic shock decreases mortality and the incidence of postoperative AEs.

Cardiovascular diseases are the leading cause of mortality rates throughout the world. Next to an insufficient number of healthy donors, this has led to increasing numbers of patients on heart transplant waiting lists with prolonged waiting times. Innovative technological advancements have led to the production of ventricular assist devices that play an increasingly important role in end stage heart failure therapy. This review is intended to provide an overview of current implantable left ventricular assist devices, different design concepts and implantation techniques. Challenges such as infections and thromboembolic events that may occur during LVAD implantations have also been discussed.

BACKGROUND: People of border areas are socio‑economically underdeveloped and medically underserved. Anemia in the growing phase of life impairs the physical and cognitive functions and in turn, hampers the overall development of the country. OBJECTIVE(S): To find out the prevalence, socio‑demographic correlates, and risk factors of anemia among adolescents residing in a border area. MATERIALS AND METHODS: A community‑based descriptive cross‑sectional study was carried out among 370 adolescents selected randomly by multistage and 30‑clusters random sampling method. Data pertaining to the socio‑demographic factors, life style and diet pattern, relevant health problems, and care‑seeking were collected by a pre‑designed schedule. Venous blood was examined by cyanmethemoglobin method to assess the Hemoglobin level. RESULTS: The overall prevalence of anemia was revealed to be 83.78% with a significant female predilection (92.59% vs. 76.92%, χ2 = 16.46 at degree of freedom = 1, P < 0.05; odds ratio (OR) = 3. 75, 95% confidence interval (CI) = 1.84‑7.77). The prevalence was higher among early adolescents compared with mid- and late-adolescents (χ2 (overall) = 9.14, at df=2, P = 0.0103) but significant female preponderance was found in the last group with χ2 = 12.5, df = 1, P < 0.05; OR(CI) = 4.29 (1.73-11.02). Anemia was revealed to be associated with lower literacy and socio-economic status (P < 0.05), bare-foot walking (P < 0.05), open-field defecation (P < 0.05), worm-infestation (P < 0.05), and care-seeking from unauthorized medical practitioners (P < 0.05) . CONCLUSION: Strict implementation of the National Anemia Control Programme as a component of school health and other health services through sub‑centers and Anganwadi Centers is the need of the moment to chain the anemia.