Waiting list and post-transplant outcome in Sweden after national centralization of heart transplant surgery.

BACKGROUND: Previous studies have demonstrated an association between transplantation rate per center and postoperative mortality after heart transplantation. In 2011, Sweden centralized heart transplants and waiting lists, reducing the number of centers from 3 to 2. We aimed to assess the active waiting time and pre- and post-transplant mortality before and after centralization. METHODS: Heart transplantations performed in Sweden between January 1, 2001 and December 31, 2020 were included. Background and donor organ supply data were collected from Scandiatransplant, the Swedish Thoracic Transplant Registry, and the Swedish Cardiac Surgery Registry. The Fine and Gray methods were applied to visualize cumulative incidence curves and conduct competing risk regressions. A Cox model was used to adjust for factors influencing time to post-transplant death. RESULTS: When comparing the two eras, the median active waiting time increased from 54 to 71 days (p = 0.015). The risk of mortality on the waiting list decreased in the later era (subhazard ratio 0.43; [95% confidence interval {CI} 0.25-0.74]; p = 0.002). The number of heart transplantation procedures (including pediatric patients) increased by 53%. There was a significant difference in organ utilization between eras (p = 0.033; chi-square test). 30-day and 1-year survival post-transplant rates for adults increased from 90.8% to 97.8% (p < 0.001) and from 87.9% to 94.6% (p < 0.001), respectively. 1-year mortality was reduced by 63% (hazard ratio 0.37; 95% CI 0.22-0.61). CONCLUSIONS: This nationwide study examined patients listed for and undergoing heart transplantation before and after the centralization of waiting lists and surgeries in Sweden. Waiting list mortality decreased, and 1-year post-transplantation survival was improved.

Diastolic Filling in Patients After Heart Transplantation Is Impaired Due to an Altered Geometrical Relationship Between the Left Atrium and Ventricle.

BACKGROUND: The geometrical relationship between atrial and ventricular short-axis cross-sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. METHODS AND RESULTS: This retrospective, cross-sectional study included 25 HTx patients (median age, 52 [range, 25-70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52-75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56-82] years), and 15 healthy controls (median age, 64 [range, 58-67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short-axis area minus the largest atrial short-axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07-0.19]) compared with controls (median, 0.05 [range, 0.03-0.08], P <0.001), whereas left ventricular volume normalized for THV (left ventricular end-diastolic volume/THV) was similar between HTx and controls (median, 0.19 [range, 0.12-0.24] and median, 0.22 [range, 0.20-0.25], respectively). At end diastole, when atrioventricular area difference reached its largest positive value in controls, 11 HTx patients (44%) had a negative atrioventricular area difference, indicating impaired diastolic filling. CONCLUSIONS: Diastolic filling is impaired in HTx patients due to an altered geometrical relationship between the left atrium and ventricle. When performing cardiac transplantation, a surgical technique that creates a smaller left atrium may improve diastolic filling by aiding hydraulic forces.

Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: Data from Swedish Heart Failure Registry.

AIMS: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. METHODS AND RESULTS: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or ≥60 ml/min/1.73 m2 , respectively. An eGFR ≥60 ml/min/1.73 m2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD. CONCLUSIONS: The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum.

How does age affect outcomes after left ventricular assist device implantation: results from the PCHF-VAD registry.

AIMS: Use of left ventricular assist devices (LVADs) in older patients has increased, and assessing outcomes in older LVAD recipients is important. Therefore, this study aimed to investigate associations between age and outcomes after continuous-flow LVAD (cf-LVAD) implantation. METHODS AND RESULTS: Cf-LVAD patients from the multicentre European PCHF-VAD registry were included and categorized into those <50, 50-64, and ≥65 years old. The primary endpoint was all-cause mortality. Among secondary outcomes were heart failure (HF) hospitalizations, right ventricular (RV) failure, haemocompatibility score, bleeding events, non-fatal thromboembolic events, and device-related infections. Of 562 patients, 184 (32.7%) were <50, 305 (54.3%) were aged 50-64, whereas 73 (13.0%) were ≥65 years old. Median follow-up was 1.1 years. Patients in the oldest age group were significantly more often designated as destination therapy (DT) candidates (61%). A 10 year increase in age was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.34, 95% confidence interval [CI] [1.15-1.57]), intracranial bleeding (HR 1.49, 95% CI [1.10-2.02]), and non-intracranial bleeding (HR 1.30, 95% CI [1.09-1.56]), which was confirmed by a higher mean haemocompatibility score (1.37 vs. 0.77, oldest vs. youngest groups, respectively, P = 0.033). Older patients suffered from less device-related infections requiring systemic antibiotics. No age-related differences were observed in HF-related hospitalizations, ventricular arrhythmias, pump thrombosis, non-fatal thromboembolic events, or RV failure. CONCLUSIONS: In the PCHF-VAD registry, higher age was associated with increased risk of mortality, and especially with increased risk of major bleeding, which is particularly relevant for the DT population. The risks of HF hospitalizations, pump thrombosis, ventricular arrhythmia, or RV failure were comparable. Strikingly, older patients had less device-related infections.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

AIMS: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. METHODS AND RESULTS: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147-823] days for women and 435 [range 190-816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50-1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33-0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. CONCLUSIONS: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.

Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Validation of cause of death classification after heart transplantation and cause-specific life expectancy compared to the general population.

BACKGROUND: Post heart-transplant survival has increased, but information is lacking on specific causes of death and life expectancy. We aimed to assess cause-specific loss of life-years compared to the general population, evaluate classification for cause of death after heart transplantation, and assess validity of cause of death data from the International Society of Heart and Lung Transplant (ISHLT) registry. METHODS: In this single center study, we included 239 heart recipients transplanted between 1988 and 2019 in Lund, Sweden (n = 239, 50% of the transplanted population where the cause of death was available). Two cardiologists retrospectively assigned causes of death according to a published classification (CLASS) in the 91 recipients who died during follow-up. Life expectancy was compared to data from the general population. RESULTS: Compared to the average Swedish population, life expectancy for heart transplant recipients was 20 years shorter (IQR 12.9-27.2). The largest number of life-years lost were for deaths due to acute (49 years) and chronic rejection (27 years). Primary graft dysfunction (24 years) accounted for 24% of deaths, followed by malignancy (20 years) and infection (17 years), each accounting for ∼20% of deaths. Use of CLASS revealed moderate inter-rater agreement (56%) and moderate agreement with the ISHLT registry (62%). CONCLUSIONS: Survival after heart transplantation was 20 years lower than in the general population. In the young, more life-years were lost due to acute graft rejection, whereas chronic graft rejection and primary graft failure were more important causes of death in older patients. Agreement was moderate between CLASS and the ISHLT registry classifications.

Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.

AIMS: Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF. METHODS AND RESULTS: All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49 ± 13 years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [ß coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P < 0.001], followed by lower mean arterial pressure (MAP) (ß coefficient 0.29; 95% CI 0.14-0.37; P < 0.001), and finally reduced cardiac index (ß coefficient 3.51; 95% CI 2.14-4.84; P < 0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output. CONCLUSIONS: In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.

Improved survival of left ventricular assist device carriers in Europe according to implantation eras: results from the PCHF-VAD registry.

AIMS: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. METHODS AND RESULTS: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23-0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43-0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39-0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02-2.75; p = 0.043). CONCLUSION: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.

Temporal trends in characteristics and outcome of heart failure patients with and without significant coronary artery disease.

AIMS: Ischaemic coronary artery disease (CAD) remains the leading cause of mortality globally due to sudden death and heart failure (HF). Invasive coronary angiography (CAG) is the gold standard for evaluating the presence and severity of CAD. Our objective was to assess temporal trends in CAG utilization, patient characteristics, and prognosis in HF patients undergoing CAG at a national level. METHODS AND RESULTS: We used data from the Swedish Coronary Angiography and Angioplasty Registry. Data on all patients undergoing CAG for HF indication in Sweden between 2000 and 2018 were collected and analysed. Long-term survival was estimated with multivariable Cox proportional hazards regression adjusted for differences in patient characteristics. In total, 22 457 patients (73% men) with mean age 64.2 ± 11.3 years were included in the study. The patients were increasingly older with more comorbidities over time. The number of CAG specifically for HF indication increased by 5.5% per calendar year (P < 0.001). No such increase was seen for indications angina pectoris and ST-elevation myocardial infarction. A normal CAG or non-obstructive CAD was reported in 63.2% (HF-NCAD), and 36.8% had >50% diameter stenosis in one or more coronary arteries (HF-CAD). The median follow-up time was 3.6 years in HF-CAD and 5 years in HF-NCAD. Age and sex-adjusted survival improved linearly by 1.3% per calendar year in all patients. Compared with HF-NCAD, long-term mortality was higher in HF-CAD patients. The risk of death increased with the increasing severity of CAD. Compared with HF-NCAD, the risk estimate in patients with a single-vessel disease was higher [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.20-1.41; P < 0.001], a multivessel disease without the involvement of left main coronary artery (HR 1.72; 95% CI 1.58-1.88; P < 0.001), and with left main disease (HR 2.02; 95% CI 1.88-2.18; P < 0.001). The number of HF patients undergoing revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) increased by 7.5% (P < 0.001) per calendar year. The majority (53.4%) of HF-CAD patients were treated medically, while a minority (46.6%) were referred for revascularization with PCI or CABG. Compared with patients treated with PCI, the proportion of patients treated medically or with CABG decreased substantially (P < 0.001). CONCLUSIONS: Over 18 years, the number of patients with HF undergoing CAG has increased substantially. Expanded utilization of CAG increased the number of HF patients treated with percutaneous coronary intervention and coronary artery bypass surgery. Long-term survival improved in all HF patients despite a steady increase of elderly patients with comorbidities.

Impact of bridging with left ventricular assist device on right ventricular function following heart transplantation.

AIMS: Patients awaiting orthotopic heart transplantation (OHT) can be bridged utilizing a left ventricular assist device (LVAD) that reduces left ventricular filling pressures, decreases pulmonary artery wedge pressure, and maintains adequate cardiac output. This study set out to examine the poorly investigated area of if and how pre-treatment with LVAD impacts right ventricular (RV) function following OHT. METHODS AND RESULTS: We prospectively evaluated 59 (LVAD n = 20) consecutive OHT patients. Transthoracic echocardiography (TTE) was performed in conjunction with right heart catheterization (RHC) at 1, 6, and 12 months after OHT. RV function TTE-parameters included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S'), fractional area change, two-dimensional RV global longitudinal strain and longitudinal strain from the RV lateral wall (RVfree). At 1 month after OHT, the LVAD group had significantly better longitudinal RV function than the non-LVAD group: TAPSE (15 ± 3 mm vs. 12 ± 2 mm, P < 0.001), RV global longitudinal strain (-19.8 ± 2.1% vs. -14.3 ± 2.8%, P < 0.001), and RVfree (-19.8 ± 2.3% vs. -14.1 ± 2.9%, P < 0.001). At this time point, pulmonary vascular resistance (PVR) was also lower [1.2 ± 0.4 Wood Units (WU) vs. 1.6 ± 0.6 WU, P < 0.05] in the LVAD group compared with the non-LVAD group. At 6 and 12 months, no difference was detected in any of the TTE and RHC measured parameters between the two groups. Between 1 and 12 months, all parameters of RV function improved significantly in the non-LVAD group but remained unaltered in the LVAD group. CONCLUSIONS: Our results indicate that pre-treatment with LVAD decreases PVR and is associated with significantly better RV function early following OHT. During the first year following transplantation, RV function progressively improved in the non-LVAD group such that at 6 and 12 months, no difference in RV function was detected between the groups.

Improved Time in Therapeutic Range with International Normalized Ratio Remote Monitoring for Patients with Left Ventricular Assist Devices.

Despite advances in therapy, bleeding and thromboembolic events are frequent complications in patients with left ventricular assist device (LVAD) support. Maintaining warfarin in therapeutic range has been shown to be more challenging in this patient population compared to other indications. Patients with LVADs on warfarin typically are within goal international normalized ratio (INR) range 36-57% of the time, compared to about 65% for other indications. The goal of this study was to evaluate if an INR remote monitoring system along with the implementation of a standardized warfarin management protocol improves warfarin time in therapeutic range (TTR) for patients with LVADs. This single-center, retrospective, observational study included 78 patients with LVADs that were followed at our academic center from January 2015 to October 2017. In October 2016, we updated our warfarin management protocol and implemented a remote monitoring system with patients' weekly INR results monitored. The primary objective of the study was to determine the difference between TTRs in remote monitoring versus standard monitoring. We found that the average TTR was significantly higher in the remote monitoring group compared to the standard monitoring cohort (61.1% vs. 40.0%, p < 0.005). However, bleeding, thrombotic incidence, and hospital readmission rates were similar between the two patient cohorts. Remote monitoring improved warfarin TTR significantly in this study and may have the potential to improve anticoagulation-related outcomes in patients with LVADs.

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV­lead pacing post LVAD implantation.

Echocardiographic assessment of chamber size and ventricular function during the first year after heart transplantation.

AIMS: Detecting changes in ventricular function after orthotopic heart transplantation (OHT) using transthoracic echocardiography (TTE) is important but interpretation of findings is complicated by lack of data on early graft adaptation. We sought to evaluate echocardiographic measures of ventricular size and function the first year following OHT including speckle tracking derived strain. We also aimed to compare echocardiographic findings to haemodynamic parameters obtained by right heart catheterization (RHC). METHODS AND RESULTS: Fifty OHT patients were examined prospectively with TTE and RHC at 1, 6, and 12 months after OHT. Left ventricle (LV) was assessed with fractional shortening, ejection fraction and systolic tissue velocities. Right ventricular (RV) evaluation included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S´) and fractional area change (FAC). LV global longitudinal and circumferential strain and RV global longitudinal strain (GLS) and RV lateral wall strain (RVfree) were analysed. No relevant changes occurred in LV echocardiographic parameters, whereas all measures of RV function improved significantly during follow-up. There was an increase in TAPSE (12.4 ± 3.3 mm to 14.4 ± 4.3 mm, p < .01), FAC (36% ± 8% to 41% ± 8%, p < .01), RV GLS (-15.8% ± 4% to -17.8% ± 3.6%, p < .01), and RVfree (-15.5% ± 3.7% to -18.6% ± 3.6%, p < .001). Between 1 and 12 months, pulmonary pressures decreased, whereas pulmonary vascular resistance did not. CONCLUSION: Stable OHT recipients reached steady state regarding LV function 1 month after transplantation. In contrast, RV function displayed gradual improvement the first year following OHT, indicating delayed RV adaptation as compared to the LV. Improved RV function parameters were independent of invasively measured pulmonary pressures.

Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Randomized trial of a left ventricular assist device as destination therapy versus guideline-directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial.

AIMS: Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx. METHODS: A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years. CONCLUSION: The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx.

Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio [HR] = 0.53 [0.30-0.95], p = 0.03), age at the time of implantation (HR = 1.28 [1.05-1.56] per decade, p = 0.02), length of stay postimplantation (HR = 1.16 [1.11-1.21] per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 [1.17-2.97], p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.

Factors influencing transfusion-associated HLA sensitization in patients bridged to heart transplantation using ventricular assist device.

BACKGROUND: Bridging heart failure patients with mechanical ventricular assist devices (VAD) enables access to transplantation. However, VAD is associated with increased risk for anti-HLA antibodies associated with rejection of subsequent allografts. Factors determining alloantibody formation in these patients remain undefined. METHODS: We performed a single-center retrospective cohort study of 164 patients undergoing heart transplantation from 2014 to 2017. Medical records including use of VAD, transfused blood products, anti-HLA antibody testing, crossmatch, and time to transplant were evaluated. RESULTS: Patients received an average of 13.8 red blood cell and 1.9 single-donor platelet units associated with VAD. There was a 28.7% increase in the incidence of anti-HLA antibodies after VAD. Development of anti-HLA antibodies did not correlate with volume or type of blood products, but with pre-VAD HLA sensitization status; relative risk of new alloantibodies in patients with pre-VAD antibodies was 3.5-fold higher than those without prior antibodies (P = .008). Development of new anti-HLA antibodies was associated with an increased time to transplant (169 vs 330 days, P = .013). CONCLUSIONS: Our findings indicate that the presence of anti-HLA antibodies pre-VAD was the most significant risk factor for developing additional antibodies post-VAD, suggesting that a subset of patients may be predisposed to alloantibody formation.