Option For Heart Failure Patients Research Articles

Non-human primate studies for cardiomyocyte transplantation-ready for translation?

Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation.

Comparative cost analysis of implanting devices in different cardiac resynchronization therapeutic strategies.

Cardiac resynchronization therapy (CRT) is an established treatment option for heart failure patients. However, the implementation of triple-chamber pacemakers can be cost-prohibitive. His-Purkinje system pacing (HPSP) can also enable cardiac resynchronization, and it can be achieved with relatively inexpensive conventional pacemakers. This article aims to comparatively evaluate the cost of implanting devices in different CRT strategies to provide meaningful guidance for clinical decision-making by electrophysiologists. Data was collected on the prices, designed life, and price/designed life of multiple mainstream models of CRT-P, CRT-D, dual-chamber pacemakers, and single-chamber pacemakers that were sold in the Chinese market in 2022. The prices, designed lives, and price/designed life of different pacemaker models were then compared. The costs of CRT-P and CRT-D (13008.44 ± 2752.30 USD and 22043.36 ± 3676.25 USD) were significantly higher than those of conventional pacemakers (dual-chamber: 11142.39 ± 4273.85 USD and single-chamber: 5634.28 ± 2032.80 USD) (p < .05). Additionally, the price/designed life of conventional pacemakers (dual-chamber: 839.63 ± 258.62 USdollar/year and single-chamber: 435.86 ± 125.44 USdollar/year) was significantly better than that of CRT-P and CRT-D (1386.91 ± 266.73 and 2585.53 ± 520.27 USdollar/year, respectively) (p < .05). Conduction system pacing (CSP)-based CRT is more cost-effective than BVP-based CRT. Furthermore, CSP-based CRT can achieve cardiac resynchronization with conventional pacemakers and may be a good option for HF patients who do not need defibrillation.

Inhibitors of sodium-glucose transport protein 2: A new multidirectional therapeutic option for heart failure patients.

Several mechanisms have been suggested to explain positive cardiovascular effects observed in studies with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The reduction in glucose reabsorption in proximal tubuli induced by SGLT2 inhibitors increases urinary glucose and sodium excretion resulting in increased osmotic diuresis and consequently in decreased plasma volume, followed by reduced preload. In addition, the hemodynamic effects of SGLT2 inhibition were observed in both hyper and euglycemic patients. Due to the complex and multidirectional effects induced by SGLT2 inhibitors, this originally antidiabetic group of drugs has been successfully used to treat patients with heart failure as well as for subjects with chronic kidney disease. Moreover, their therapeutic potential seems to be even broader than the indications studied to date.

Standardized papillary muscle relocation for type IIIb secondary mitral regurgitation improves 2-year outcome.

The major drawback of isolated annuloplasty for treatment of secondary mitral regurgitation (SMR) with restricted leaflet motion during systole (type IIIb) is the recurrence of SMR, leading to adverse clinical outcome. Additional papillary muscle relocation (PMR) specifically addresses leaflet tethering to restore mitral valve geometry. We aimed to compare the 2-year outcome of annuloplasty with additional PMR vs isolated annuloplasty. A total of 105 consecutive type IIIb SMR patients with preoperative left ventricular (LV) ejection faction <45%, left ventricular end-diastolic diameter >55 mm and a tenting height >10 mm reached 2-year postoperative follow-up after mitral valve repair and were included in the current analysis. A total of 51 patients underwent annuloplasty and additional PMR (study group). A total of 54 patients underwent isolated annuloplasty (control group). Primary composite study end point comprised death or recurrence of mitral regurgitation≥2 at 2 years postoperatively. Echocardiographic baseline variables indicating the severity of LV dysfunction and mitral leaflet tethering were similar. Procedural and periprocedural outcome was comparable in both groups. The primary composite end point was significantly improved in the study group (19.6% [10/51]) in comparison to the control group (44.4% [24/54]; P = 0.009). Two-year all-cause mortality was 7.8% [4/51] in the study group vs 18.5% [10/54] in the control group (P = 0.098). After 2 years, a significant improvement in New York Heart Association functional class as compared to the baseline values was observed in the study group. Additional PMR to treat SMR type IIIb resulted in an improved 2-year outcome in comparison to isolated annuloplasty. PMR specifically addressing mitral leaflet tethering represents a valid therapeutic option for heart failure patients with SMR type IIIb.

Comparative computational analysis of PASCAL and MitraClip implantation in a patient-specific functional mitral regurgitation model.

Transcatheter mitral leaflet approximation with MitraClip has proven to be a viable treatment option for heart failure patients with functional mitral regurgitation (MR). PASCAL is a similar clip device, but it has design features that differentiate it from MitraClip. The effects of the different clip designs are largely unknown. In this study, using a patient-specific, mitral valve-left ventricle heart model, we performed finite-element (FE) simulations to provide a head-to-head comparison of the post-operative effects that PASCAL and MitraClip have on mitral valve (MV) geometry and biomechanics in a functional MR patient. The two devices were modeled as approximations of the real devices, and three implantation configurations were simulated for each device. The results showed that for this patient case, PASCAL caused less MV deformation than MitraClip. Additionally, PASCAL implantation reduced the stresses and strains in the MV leaflets compared to pre-repair conditions, while MitraClip implantation caused them to increase. Although complete coaptation was not achieved, both devices improved leaflet coaptation and were viable MR treatment options. The FE simulations in this study can be used to quantify biomechanics involved in clip treatments and improve our understanding of complex interactions between human hosts and percutaneous clip devices.

Pathways to Clinical Cardiac Xenotransplantation.

Heart transplantation is the only long-lasting lifesaving option for patients with terminal cardiac failure. The number of available human organs is however far below the actual need, resulting in substantial mortality of patients while waiting for a human heart. Mechanical assist devices are used to support cardiac function but are associated with a high risk of severe complications and poor quality of life for the patients. Consistent success in orthotopic transplantation of genetically modified pig hearts into baboons indicates that cardiac xenotransplantation may become a clinically applicable option for heart failure patients who cannot get a human heart transplant. In this overview, we project potential paths to clinical cardiac xenotransplantation, including the choice of genetically modified source pigs; associated requirements of microbiological, including virological, safety; optimized matching of source pig and recipient; and specific treatments of the donor heart after explantation and of the recipients. Moreover, selection of patients and the regulatory framework will be discussed.

B-PO04-034 WIRELESS CARDIAC RESYNCHRONIZATION THERAPY: 1-YEAR FOLLOW-UP AFTER IMPLANTATION OF TOTALLY LEADLESS CRT-PACEMAKER SYSTEMS IN TWO ADULTS

Cardiac resynchronization therapy (CRT) is an established treatment option for heart failure patients. However, up to 20% of CRT candidates are non-responders due to suboptimal pacing sites. An endocardial wireless technology based on energy transmission by ultrasound through the intercostal space can be used for leadless LV cardiac stimulation. In combination with a co-implanted leadless RV pacemaker, CRT can be achieved. We implanted a totally leadless pacemaker system (Micra VR TCP, Medtronic and Wireless Stimulation Endocardially for CRT, WiSE-CRT, EBR Systems Inc.) in two patients. In this report we report the follow-up until 1 year after implantation. N/A Patient #1 was an 82-year old man with ischemic cardiomyopathy and permanent atrial fibrillation who developed a broad left bundle branch block after TAVR. To avoid worsening of the preexisting tricuspid regurgitation, we decided to implant a totally leadless CRT device. Patient #2 (male, 77 years) with dilated cardiomyopathy and persistent bradyarrhythmia had a CRT system explanted due to previous pocket infection. This led to the decision to re-implant a leadless CRT system. Immediately after the WISE-CRT system was activated, biventricular pacing showed narrowing of the QRS width (pat. #1: 170 ms to 130 ms, pat. #2: 145 ms to 120 ms). During one year follow-up in patient #1, LV-EF improved from 20 % to 40 %. The degree of MR and TR improved from °III to °I-II. Dyspnea improved from NYHA class IV to II. NT-proBNP levels also decreased from 2440 to 1118 pg/ml. The CRT system showed a LV-RV tracking rate of 96-97 %. In patient #2 the LV-EF remained stable at 30 %. The degree of MR and TR were moderate and unchanged to baseline. The patient was hospitalized twice due to congestive heart failure. CRT controls showed a LV-RV tracking rate of 95-98 %. Transmit levels (TL, corresponds to pacing threshold) were significantly higher in patient #2 than in patient #1 indicating intermittent non capture in patient #2 (pat. #1: TL 3/0.5 to 2/0.3 ms, pat. #2: TL 6/0.8 to 6/1.5 ms). We found implantation of a totally leadless CRT-P system feasible and safe in two patients. Like in conventional CRT, the rate of biventricular pacing is crucial for the effect of resynchronization.

Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.

Functional mitral regurgitation (FMR) is a sequel of left ventricular (LV) remodelling in heart failure patients. Relocation of both papillary muscles aims to specifically address mitral leaflet tethering to improve long-term durability of modern FMR repair. Nevertheless, the prognostic impact of the underlying cardiomyopathy on the outcome after FMR repair is unknown. We analysed 84 consecutive heart failure patients with severe FMR, LV ejection fraction <40%, LV end-diastolic diameter ≥55 mm and tenting height >10 mm, who underwent ring annuloplasty and simultaneous bilateral papillary muscles relocation between June 2016 and March 2019. One-year outcome of 54 patients with ischaemic cardiomyopathy ('ICM group') was prospectively compared to the remaining 30 patients with dilated cardiomyopathy ('DCM group'). One-year survival was similar in both groups (96% in the 'ICM group' vs 97% in the 'DCM group'; P = 0.93). Furthermore, primary composite outcome (i.e. freedom from death or mitral regurgitation ≥ 2) at 1-year postoperatively was comparable between the study groups (94%in the 'ICM group' vs 87% in the 'DCM group'; P = 0.10). LV end-diastolic diameter 1-year after surgery was significantly reduced, as compared to preoperative values, in the 'DCM group' (P = 0.018), but not in the 'ICM group' (P = 0.058). Improvement of New York Heart Association functional class and reduction of serum levels of N-terminal pro-B natriuretic peptide at 1 year was comparable in both study groups. Standardized relocation of both papillary muscles to correct FMR resulted in very satisfactory in-hospital and 1-year outcomes, in both ICM and DCM. DCM patients showed similar improvement in heart failure symptoms and LV re-remodelling compared to ICM patients. Subannular repair is developing towards a valid therapeutic option in heart failure patients presenting with severe FMR.

Ferric carboxymaltose for the treatment of iron-deficient heart failure patients: a systematic review and meta-analysis.

AimsIntravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta‐analyses have been underpowered to detect significant differences. We sought to conduct an updated meta‐analysis using recently published RCT data.Methods and resultsOnline databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron‐deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all‐cause mortality, and cardiovascular mortality. Meta‐analysis was performed using a fixed‐effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63–0.90; I 2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54–0.85; I 2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59–0.86; I 2 = 56%). However, FCM had no significant effect on the risk of all‐cause (OR = 0.97; 95% CI = 0.73–1.28; I 2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69–1.27; I 2 = 0%).ConclusionsFerric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all‐cause and cardiovascular mortality in iron‐deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients.

Ultrafiltration trough peritoneal dialysis in refractory congestive heart failure patients: one center experience

Background: Hypervolemia is an important consequence of heart failure (HF) that leads to poor quality of life and frequent hospitalizations. Ultrafiltration (UF) with dialysis is an option for HF patients who are resistant or inappropriate for diuretics. Peritoneal dialysis (PD) can be a long-term efficient solution for hypervolemia in appropriate HF patients. Material and Methods: We retrospectively evaluated PD patients in our center in order to determine the ones whose indication was UF for volume control because of HF between January 2015 and January 2020. Results: 4 (2 females, 68.75±4.27 years old) HF patients who had a poor volume control on diuretic based regimen were on PD for UF. PD treatment was planned as a daily single exchange with icodextrin in whom all had preserved renal function. In one patient one daily exchange with an amino acid-based PD solution was added. The exchange volume was between 1000 and 1500 mL, dwell time was 9 to 14 hours, and UF was 200 to 1100 mL. During the follow-up, patients lost adequate weight and none of them were hospitalized because of hypervolemia. Conclusions: UF through PD in HF patients provides effective volume control, relief of symptoms, and avoids frequent hospitalizations. A single daily exchange with icodextrin can be adequate for hypervolemic, well-selected HF patients.

Improving Gene Therapy Efficacy Using Impella

Gene therapy is a promising option for heart failure patients, but there remains a lack of effective delivery mechanisms. The Impella device is a heart pump that can increase coronary flow and pressure, important factors that determines efficacy of gene transduction when using intracoronary delivery. Because it also lends hemodynamic support, the Impella can be coupled with balloon coronary occlusion to increase cardiac vector dwell time. We hypothesized that use of the Impella offers safe and efficient delivery of genes using intracoronary administration of adeno-associated viral (AAV)-6. AAV6 encoding luciferase gene (5.0 × 10E13) was injected into the coronary artery one week after MI induction in Yorkshire pigs. A total of twelve pigs were allocated to one of the following groups: slow antegrade delivery (n=3), slow antegrade delivery with Impella (n=3), delivery during coronary artery occlusion with Impella hemodynamic support (n=3), delivery during coronary artery and sinus occlusions with Impella hemodynamic support (CA + CS, n=3), Four weeks later, tissues were harvested from various heart regions and other organs to assess luciferase expression and viral uptake. Impella support offered safe vector delivery during 1-2 minutes of CA and CS occlusion. Impella + coronary artery block enhanced luciferase expression globally in the heart but not in non-cardiac tissues, such as liver, as compared to injection without coronary artery block. Impella with CA + CS block even further increased luciferase expression by increasing viral uptake, as evidenced by increased vector genome in the tissues detected by PCR. At the infarct border zone, an important area for cardiac gene therapy, CA + CS occlusion led to greater than 300-fold increase in luciferase (p=0.005) compared to viral injection alone. Impella unloading with CA + CS occlusion dramatically improves AAV gene expression in the heart without increasing off-target expression; it is thus a promising method for clinical application of cardiac gene therapy.

Peritoneal dialysis as therapeutic option in heart failure patients.

AimsEach episode of acute decompensated heart failure (HF) incrementally adds to mortality. Peritoneal dialysis (PD) offers an alternative therapeutic option in refractory HF and reduces the incidence of decompensation episodes. The objective of this study was to determine the efficacy of PD, in terms of functional status, surrogate endpoints, rate of hospitalizations, and mortality.Methods and resultsThis study is based on the registry of the German Society of Nephrology, involving 159 patients receiving PD treatment due to refractory HF between January 2010 and December 2014. Body weight was reduced by PD (82.2 ± 14.9 to 78.4 ± 14.8 kg, P < 0.001), and significant improvements in New York Heart Association functional class (3.38 ± 0.55 to 2.85 ± 0.49, P < 0.001) were found already after 3 months. Left ventricular ejection fraction did not change (31.5 ± 13.8 to 34.0 ± 15.7%, P = 0.175). C‐reactive protein improved with PD treatment (33.7 ± 52.6 to 17.1 ± 26.3 mg/L, P = 0.004). Blood urea nitrogen/creatinine ratio decreased significantly (148.7 ± 68.3 to 106.7 ± 44.8 mg/dL, P < 0.001). Hospitalization rates decreased significantly (total number 2.86 ± 1.88 to 1.90 ± 1.78, P = 0.001, and 39.2 ± 30.7 to 27.1 ± 25.2 days, P = 0.004). One year mortality was 39.6% in end‐stage HF patients treated with PD.ConclusionsPeritoneal dialysis offers an additional therapeutic option in end‐stage HF and is associated with improved New York Heart Association classification and reduced hospitalization. Although PD treatment was associated with various benefits, further studies are necessary to identify which patients benefit the most from PD.

Exercise training program in patients with NYHA III class systolic heart failure - Parallel comparison to the effects of resynchronization therapy

PurposeThe aim of this study was to assess exercise capacity and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF) in NYHA III functional class, after cardiac resynchronization therapy (CRT) or implantable cardioverter-defibrillator (ICD) implantation followed by 6 months of supervised rehabilitation in ICD patients. Materials and methodsThe study included patients with HFrEF and impaired left ventricle systolic function (LVEF ≤ 35%), divided into two groups: CRT group - patients after CRT-D implantation > six weeks, and ICD-rehab group - patients after ICD implantation > six weeks, followed by 6 months of supervised aerobic interval training and the conditioning exercises. At baseline and after 6 months in all the patients cardiopulmonary exercise tests (CPX) and standard echocardiographic examinations were performed. ResultsThe study included 61 patients (49–77 years) with HFrEF. At baseline, the values of CPX parameters were similar in both groups. After completing training almost all CPX parameters in the ICD-rehab group significantly improved, except for anaerobic threshold (AT). In the CRT group significant improvements were found in 2 parameters: peak oxygen uptake (VO2) and exercise tolerance (metabolic equivalents, METs). Significant reductions in left and right ventricle diameters and an increase in LVEF were observed in both groups after 6 months. ConclusionsSignificant improvement in exercise tolerance capacity and increase of LVEF were observed in similar extent both in heart failure patients with CRT and with ICD undergoing the rehabilitation program. Regular, controlled exercise trainings provided additional, safe and easy to conduct therapeutic option for heart failure patients with no indications for CRT.

Alleviation of VAD Coordinator Time Burden and Empowermentof HVAD Patients in Order to Improve Outcomes

With the continued increase of LVAD’s as a viable therapy option for heart failure patients, the role of the VAD Coordinator has become increasingly more complex and time demanding. The intent of this International Consortium of Circulatory Assist Clinicians (ICCAC) and Medtronic survey is to understand the time burden of VAD Coordinators and how industry can address these challenges through partnerships that continually improve patient outcomes.

Cardiac Compression Devices: Alternative Technology and Innovative Concept

: Heart failure is a leading cause of death around the world. Heart transplantation is the only reliable therapy for improving functional capacity, quality of life, life expectancy, and limiting the options for heart failure patients. In fact, a large number of patients with severe heart failure in need of heart transplantation are unable to receive therapy with up to 30% mortality before a heart is donated. In recent decades, cardiac replacement and assisting therapies have presented promising outcomes to treat these end-stage patients as alternative solutions. These devices are capable of providing temporary to permanent, partial or full assistance. Such devices can be divided into two categories based on location and mechanism of augmentation: 1) devices exposed directly to blood including ventricular assistive devices (VADs) and total artificial hearts (TAHs) and 2) devices that augment cardiac output through compression of ventricles or another part of circulatory system with no direct contact to blood such as extra-cardiac compression devices (ECCDs). In recent years, novel ECCDs which compress tissue and muscles to indirectly assist blood pumping have been developed to circumscribe problems associated with blood-contacting devices and the risks involved with piercing arterial and ventricular walls. Not only do ECCDs aim to reduce risks from the patient and surgeon perspective, the complexity of engineering an intra-corporeal extra-cardiac device is also reduced.

Abstract 165: The Transcriptional Cofactor Eyes Absent 4 Is A Critical Regulator In Cardiac Physiology

Introduction: Eyes absent 4 (Eya4) is a transcription cofactor involved in a number of cellular and developmental processes. We have previously shown that a truncating mutation in Eya4, E193, causes hearing impairment followed by terminal heart failure suggesting Eya4 is a regulator in cardiac physiology. Methods and Results: Transgene- or adenovirus mediated overexpression of Eya4 or E193 altered the expression of p27kip1, a critical mediator of cardiac hypertrophy in adult cardiomyocytes. Luciferase reporter and EMSA assays revealed that Eya4 directly binds to and suppresses p27kip1 promoter activity, while E193 exerts an opposing effect, respectively. Activity and phosphorylation of downstream molecules were significantly altered in Eya4 and E193 transgenic (TG) mice in a contradictory manner. Cardiac phenotypes evolved in both TG models already under basal conditions. Eya4 TG hearts developed hypertrophy as judged by increases in heart weight and cross-sectional cell surfaces and re-activation of fetal genes as well as fibrosis. E193 TG animals showed onset of DCM along with wall thinning, ventricular dilation, fibrosis and slightly compromised cardiac function. These two distinct cardiac phenotypes were even more aggravated upon pressure overload or Angiotensin II infusion. Finally, we just recently identified a new mutation in Eya4, E215, which also causes hearing impairment and heart failure. Conclusion: Our data indicate that Eya4, in a physical complex with Six1, plays a critical role in regulating normal cardiac function via p27/CK2-α/HDAC2 and allude that mutations within the Exa4/Six1 transcriptional complex interfere with this newly established signalling pathway, finally leading to age-related onset of cardiomyopathy. Clinical Perspective: Gaining a better understanding of this disease mechanism could help identify new treatment options for heart failure patients.

Clinical outcome after 1 year of cardiac resynchronisation therapy: national results from the European CRT survey

Cardiac resynchronisation therapy (CRT) is an established treatment option for heart failure patients with electromechanical dyssynchrony. Between 2008 and 2010, the Heart Failure Association (HFA) and the European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) initiated the European CRT survey to describe the current practice and short-term clinical outcome associated with CRT implantations in 13 countries. One year follow-up data from 150 patients collected in 10 Austrian centres are presented in comparison to the total 1,969 patients enrolled throughout Europe. In most cases (n = 120), CRT-D devices were implanted, while CRT-P devices were used in only 23 %. After 12 ± 3 months, mortality and hospitalisation rates reached 10 and 37 %, respectively. New York Heart Association (NYHA) functional classes improved significantly: NYHA I/II/III/IV were found before implantation in 2/20/71/7 % and after 1 year follow-up in 35/51/9/5 % of the patients, respectively. Left ventricular ejection fraction improved from 27 ± 8 % to 35 ± 10 %, left ventricular end-diastolic diameters were reduced from 65 ± 10 mm to 59 ± 5 mm. Median NT-proBNP was reduced from 1,886 to 997 pg/ml, QRS duration diminished from 158 ± 34 to 147 ± 27 ms. In conclusion, the Austrian data from the CRT survey confirms the efficacy of CRT in heart failure patients, but outlines that these patients still suffer from a high mortality and cardiovascular (CV) hospitalisation rate.

Heterotopic heart transplant: is there an indication in the continuous flow ventricular assist device era?

Heterotopic heart transplantation (HHTx) is a therapeutic option in heart failure patients with fixed elevated pulmonary hypertension. However, survival is poorer in HHTx recipients, and with improving results in continuous flow ventricular assist devices (VADs), many patients can be bridged to allow normalization of pulmonary artery pressures, making them orthotopic heart transplant (OHTx) candidates. Thus, the aim of this study was to analyse the survival of our HHTx cohort and compare them with our VAD bridge patients. A retrospective review of 342 heart transplant patients (315 OHTx and 27 HHTx) performed at our institution over 15 years was compared with 124 bridge-to-transplant VAD patients over the same time period, of whom 69 received an OHTx. Pulmonary artery pressures before and after VAD implant were analysed. Survival was analysed using both univariate and multivariate analyses. HHTx recipients were significantly older, and the donor allografts were older, smaller and had longer ischaemic times than the OHTx cohort. Comparison of the VAD types implanted (pulsatile vs continuous) showed significantly longer time supported on the continuous devices with significantly fewer deaths than the pulsatile devices. The continuous devices were successful in reducing pulmonary artery pressures pretransplant. The HHTx cohort had a significantly poorer survival than the OHTx cohort (P=0.002). Survival on a continuous device and then OHTx was significantly better than either HHTx or pulsatile device support. The main indication for HHTx, namely fixed elevated pulmonary hypertension in heart failure patients, can be safely and effectively treated by continuous flow bridge to transplant with superior survival.

Effect of cannula position in the thoracic aorta with continuous left ventricular support: four-dimensional flow-sensitive magnetic resonance imaging in an in vitro model

Left ventricular assist devices (LVADs) have become an important treatment option for heart failure patients. However, altered blood flow patterns are suspected to affect perfusion in the aorta or cause structural changes to the aortic root, leading to regurgitation and valve dysfunction or thrombus formation. The purpose of this study was to evaluate flow patterns in a realistic in vitro model system using four-dimensional flow-sensitive magnetic resonance imaging. A magnetic resonance compatible model system was developed consisting of an aorta connected to a VAD simulating the pulsatile flow of the native heart. An LVAD was connected to the aorta model via three different cannula positions. Flow patterns in the entire system as well as flow rates in predefined positions for reduced and zero cardiac output were evaluated. Cannula position influences flow patterns and flow rates in the entire thoracic aorta. For a residual cardiac output, a larger anastomosis and a decreased flow rate of the LAVD result in a higher flow rate and smaller retrograde flow in the ascending aorta when compared with a smaller anastomosis or a cannula position in the descending aorta. Pronounced flow turbulences in the aorta were observed for the cannula position in the descending aorta. In the setting of reduced cardiac output, as commonly observed in patients on LVAD therapy, a large anastomosis to the ascending aorta for the outflow cannula induces the least-adverse flow patterns in the aortic root. Our approach may aid in a better understanding of LVAD-induced flow-pattern changes. Optimization of the cannula position and anastomosis may help to prevent the progression of aortic valve-regurgitation and thrombus formation.

Who needs a transplant and when?

Heart transplantation remains the treatment of choice for patients with advanced heart failure. We review the current definition of optimal therapy, prediction of prognosis and revisit contraindications for transplant. Clinical trials of eplerenone and ivabradine were associated with improved prognosis, whereas others (nesiritide) were disappointing. Advances in cardiac resynchronization therapy and ventricular assist devices (VAD) have resulted in an expansion of their indications. Advances in catheter ablation for ventricular tachycardia have made this an uncommon indication for heart transplantation. Surgical ventricular reconstruction and mitral valve intervention have not resulted in survival benefit. Bypass surgery was associated with a lower mortality from cardiovascular causes. Prognostic risk scores have been developed in heart failure patients; however, ongoing refinements are needed. Selected patients with diabetes, HIV and pretransplant malignancy, now have favourable outcomes after heart transplantation. VAD as bridge to candidacy is an option in heart failure patients with 'fixed' pulmonary hypertension. Alternate listing strategies have also been studied to provide high-risk patients with an opportunity for heart transplantation. Heart failure patients should be on current optimal medical and device therapy with a poor prognosis before consideration for heart transplantation. An individualized approach to heart transplantation assessment is recommended.