Heart transplantation in patients bridged with mechanical circulatory support: outcome comparison with matched controls.

AIMS: Due to the shortage of heart donors, increasing numbers of heart transplantation (HTx) candidates are receiving long-term mechanical circulatory support (MCS) as bridge-to-transplantation. Treatment with MCS is associated with increased formation of anti-human leukocyte antigen antibodies (allosensitization), but whether this affects post-HTx outcomes is unclear. METHODS AND RESULTS: We included all adult patients who received long-term MCS as bridge-to-transplantation and underwent subsequent HTx at our centre between 2008 and 2018. We also enrolled medically treated HTx recipients without prior MCS as controls. These controls were matched by age, sex, diagnosis, and transplantation era. Outcome parameters were compared between the two study groups. A total of 126 patients (48 ± 15 years, 84% male) were included of whom 64 were bridged with MCS and 62 were matched controls. Pre-HTx allosensitization occurred more frequently in the MCS group than in the control group (27% vs. 11%, P = 0.03). At post-HTx year 10, the overall survival probability was 84% among patients treated with MCS and 90% among those medically managed (P = 0.32). At post-HTx year 1, freedom from treated rejections (≥ISHLT 2R) was 69% in the MCS group and 70% in the control group (P = 0.94); and freedom from any rejection was 8% and 5%, respectively (P = 0.98). There were no differences in renal function or cardiac allograft vasculopathy (grade ≥ 1) between groups at 1, 3, and 5 years post-HTx. CONCLUSIONS: Although patients treated with MCS had a higher frequency of pre-HTx allosensitization, there were no significant differences in post-HTx graft survival, biopsy-proven rejections, or renal function as compared with patients not bridged with MCS.

A novel echocardiographic right ventricular dysfunction score can identify hemodynamic severity profiles in left ventricular dysfunction.

PURPOSE: Recognition of congestion and hypoperfusion in patients with chronic left ventricular dysfunction (LVD) has therapeutic and prognostic implications. In the present study we hypothesized that a multiparameter echocardiographic grading of right ventricular dysfunction (RVD) can facilitate the characterization of hemodynamic profiles. METHODS: Consecutive patients (n = 105, age 53 ± 14 years, males 77%, LV ejection fraction 28 ± 11%) referred for heart transplant or heart failure work-up, with catheterization and echocardiography within 48 h, were reviewed retrospectively. Three hemodynamic profiles were defined: compensated LVD (cLVD, normal pulmonary capillary wedge pressure (PCWP < 15 mmHg) and normal mixed venous saturation (SvO2 ≥ 60%)); decompensated LVD (dLVD, with increased PCWP) and LV failure (LVF, increased PCWP and reduced SvO2). We established a 5-point RVD score including pulmonary hypertension, reduced tricuspid annular plane systolic excursion, RV dilatation, ≥ moderate tricuspid regurgitation and increased right atrial pressure. RESULTS: The RVD score [median (IQR 25%;75%)] showed significant in-between the three groups differences with 1 (0;1), 1 (0.5;2) and 3.0 (2;3.5) in patients with cLVD, dLVD and LVF, respectively. The finding of RVD score ≥ 2 or ≥ 4 increased the likelihood of decompensation or LVF 5.2-fold and 6.7-fold, respectively. On the contrary, RVD score < 1 and < 2 reduced the likelihood 11.1-fold and 25-fold, respectively. The RVD score was more helpful than standard echocardiography regarding identification of hemodynamic profiles. CONCLUSIONS: In this proof of concept study an echocardiographic RVD score identified different hemodynamic severity profiles in patients with chronic LVD and reduced ejection fraction. Further studies are needed to validate its general applicability.

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.

The trajectory of renal function following mechanical circulatory support and subsequent heart transplantation.

AIM: Patients with advanced heart failure (HF) frequently suffer from renal insufficiency. The impact of durable mechanical circulatory support (MCS) and subsequent heart transplantation (HTx) on kidney function is not well described. METHODS AND RESULTS: We studied patients with advanced HF who received durable MCS as bridge to transplantation (BTT) and underwent subsequent HTx at our centre between 1996 and 2018. Glomerular filtration rate (GFR) was measured by 51 Cr-EDTA or iohexol clearance during heart failure work-up; 3-6 months after MCS; and 1 year after HTx. Chronic kidney disease (CKD) was classified according to KDIGO criteria based on estimated GFR. A total of 88 patients (46 ± 15 years, 84% male) were included, 63% with non-ischaemic heart disease. The median duration of MCS-treatment was 172 (IQR 116-311) days, and 81 subjects were alive 1 year after HTx. Measured GFR increased from 54 ± 19 during HF work-up to 60 ± 16 mL/min/1.73 m2 after MCS (P < 0.001) and displayed a slight but nonsignificant decrease to 57 ± 22 mL/min/1.73 m2 1 year after HTx (P = 0.38). The trajectory of measured GFR did not differ between pulsatile and continuous flow (CF) pumps. Among patients 35-49 years and those who were treated in the most recent era (2012-2018), measured GFR increased following MCS implantation and subsequent HTx. Estimated GFR displayed a similar course as did measured GFR. CONCLUSIONS: In patients with advanced heart failure, measured GFR improved after MCS with no difference between pulsatile and CF-pumps. The total study group showed no further increase in GFR following HTx, but in certain subgroups, including patients aged 35-54 years and those treated during the latest era (2012-2018), renal function appeared to improve after transplant.

Diagnosis, management, and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience.

BACKGROUND: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM. METHOD: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020. RESULTS: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5-60.9] and 2.98 [0.6-40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001). CONCLUSION: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.

Durable circulatory support with a paracorporeal device as an option for pediatric and adult heart failure patients.

OBJECTIVES: Not all patients in need of durable mechanical circulatory support are suitable for a continuous-flow left ventricular assist device. We describe patient populations who were treated with the paracorporeal EXCOR, including children with small body sizes, adolescents with complex congenital heart diseases, and adults with biventricular failure. METHODS: Information on clinical data, echocardiography, invasive hemodynamic measurements, and surgical procedures were collected retrospectively. Differences between various groups were compared. RESULTS: Between 2008 and 2018, a total of 50 patients (21 children and 29 adults) received an EXCOR as bridge to heart transplantation or myocardial recovery. The majority of patients had heart failure compatible with Interagency Registry for Mechanically Assisted Circulatory Support profile 1. At year 5, the overall survival probability for children was 90%, and for adults 75% (P = .3). After we pooled data from children and adults, the survival probability between patients supported by a biventricular assist device was similar to those treated with a left ventricular assist device/ right ventricular assist device (94% vs 75%, respectively, P = .2). Patients with dilated cardiomyopathy had a trend toward better survival than those with other heart failure etiologies (92% vs 70%, P = .05) and a greater survival free from stroke (92% vs 64%, P = .01). Pump house exchange was performed in nine patients due to chamber thrombosis (n = 7) and partial membrane rupture (n = 2). There were 14 cases of stroke in eleven patients. CONCLUSIONS: Despite severe illness, patient survival on EXCOR was high, and the long-term overall survival probability following heart transplantation and recovery was advantageous. Treatment safety was satisfactory, although still hampered by thromboembolism, mechanical problems, and infections.

Risk stratification in chronic thromboembolic pulmonary hypertension predicts survival.

OBJECTIVES: To investigate if the pulmonary arterial hypertension (PAH) risk assessment tool presented in the 2015 ESC/ERS guidelines is valid for patients with chronic thromboembolic pulmonary hypertension (CTEPH) when taking pulmonary endarterectomy (PEA) into account. Design. Incident CTEPH patients registered in the Swedish PAH Registry (SPAHR) between 2008 and 2016 were included. Risk stratification performed at baseline and follow-up classified the patients as low-, intermediate-, or high-risk using the proposed ESC/ERS risk algorithm. Results. There were 250 CTEPH patients with median age (interquartile range) 70 (14) years, and 53% were male. Thirty-two percent underwent PEA within 5 (6) months. In a multivariable model adjusting for age, sex, and pharmacological treatment, patients with intermediate-risk or high-risk profiles at baseline displayed an increased mortality risk (Hazard Ratio [95% confidence interval]: 1.64 [0.69-3.90] and 5.39 [2.13-13.59], respectively) compared to those with a low-risk profile, whereas PEA was associated with better survival (0.38 [0.18-0.82]). Similar impact of risk profile and PEA was seen at follow-up. Conclusion. The ESC/ERS risk assessment tool identifies CTEPH patients with reduced survival. Furthermore, PEA improves survival markedly independently of risk group and age. Take home message: The ESC/ERS risk stratification for PAH predicts survival also in CTEPH patients, even when taking PEA into account.

Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients.

AIMS: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. METHODS AND RESULTS: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7-11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7-11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. CONCLUSIONS: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.

Sex-specific differences and survival in patients with idiopathic pulmonary arterial hypertension 2008-2016.

BACKGROUND: Women with idiopathic pulmonary arterial hypertension (IPAH) have been found to have a worse haemodynamic status at diagnosis, but better survival than men. Over the past decade, demographics have changed and new treatments have become available. The objective of this study was to investigate sex differences in an incident IPAH population diagnosed between 2008 and 2016. METHODS: Differences in clinical characteristics of patients included in the Swedish Pulmonary Arterial Hypertension Register (SPAHR) were analysed at the time of diagnosis. Survival by sex was investigated using Cox proportional hazard regression and Kaplan-Meier curves. RESULTS: The study included 271 patients diagnosed with IPAH, median age was 68 (1st-3rd quartiles 54-74) years and 56% were women. At diagnosis, women were younger, had lower pulmonary vascular resistance and fewer comorbidities and more often received a combination of PAH-targeted therapies than men. Men had worse survival rates than women (hazard ratio 1.49; CI 1.02-2.18; p=0.038), but this difference did not remain after adjustment for age (hazard ratio 1.30; CI 0.89-1.90; p=0.178). CONCLUSIONS: Men with incident IPAH have worse crude survival than women. This is due to women being younger with a less pronounced comorbidity burden than men at the time of diagnosis.

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial.

Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 µg/kg+0.1 µg/kg per minute) or dobutamine (7.5  µg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.

[Heart transplantation in AL amyloidosis]. / Livräddande behandling vid hjärtamyloidos av AL-typ - Hjärttransplantation med efterföljande autolog stamcellstransplantation kan ge goda resultat.

Amyloidosis is a disease complex characterized by the deposition of protein fibrils in various tissues, which leads to structural and functional derangement of the affected organ. There are different types of amyloidosis categorized on the basis of the type of protein fibrils deposited. Cardiac involvement has been predominantly noted in amyloid light chain (AL) amyloidosis and is the major prognostic determinant and influences the therapeutic strategy.  In AL amyloidosis, heart transplantation is generally not recommended because of a high risk of recurrence in the transplanted heart and poor survival rate. However, a favourable outcome can be achieved if heart transplantation is followed by an autologous stem cell transplantation (ASCT). We describe our experience from the two first patients with AL amyloidosis treated with heart transplantation and subsequent ASCT at Sahlgrenska University Hospital.

Continuous improvement in outcome after heart transplantation - Long-term follow-up after three decades of experience.

AIMS: Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. We report on the long-term outcome after HTx at our centre and investigate trends in outcome over time. METHODS: During the period, between 1984 and 2014, a total of 610 HTx procedures were performed in 595 patients (median 48years; IQR 31-57years; range 24days-71years; mean 43years; 75% male) in our institution. Long-term outcome was investigated in the whole cohort, among children (n=76), bridged with mechanical circulatory support (MCS, n=131), re-transplanted (n=17), and concomitant kidney transplantation (n=12). RESULTS: Long-term survival was at 1, 5, 10, 15 and 20years: 86% (95CI 0.83-0.89); 77% (95CI 0.73-0.80); 63% (95CI 0.59-0.68); 48% (95CI 0.43-0.54) and 30% (95CI 0.25-0.36), respectively. The median survival for the whole cohort was 14.1years. Patients transplanted during the most recent time period (2010-2014) had a better survival compared to previous eras, with a 1- and 3-year survival of 94% (95CI 0.89-0.97) and 93% (95CI 0.88-0.96), respectively (p<0.001). However, when survival was analysed for long-term MCS (n=80) versus short term MCS (n=35), there was a significantly poorer survival for the short-term MCS group (p=0.001). Independent predictors of long-term mortality included recipient age (p=0.041); previous smoking (p=0.034); ischemic heart disease (p=0.002); and preoperative ventilator therapy (p=0.004). CONCLUSIONS: We have shown that continuous improvement in outcome after HTx still occurs. In the last time era, direct transplantation from short-term MCS was abandoned, which may have inflicted outcome during the last time era.

Are biventricular assist devices underused as a bridge to heart transplantation in patients with a high risk of postimplant right ventricular failure?

OBJECTIVE: Right ventricular failure in patients treated using left ventricular assist devices is associated with poor outcomes. We assessed the strategy of preplanned biventricular assist device implantation in patients with a high risk for right ventricular failure. METHODS: Between 2010 and 2014, we assigned 20 patients to preplanned biventricular assist device and 21 patients to left ventricular assist device as a bridge to heart transplantation on the basis of the estimated risk of postimplant right ventricular failure. Preimplant characteristics and postimplant outcomes were compared between the 2 groups. RESULTS: Patients with a biventricular assist device were younger, more often female, and more frequently had nonischemic heart disease than left ventricular assist device recipients. At preoperative assessment, biventricular assist device recipients had poorer Interagency Registry for Mechanically Assisted Circulatory Support profiles, a lower cardiac index, and more compromised right ventricular function. Survival on device to heart transplantation/weaning/destination for biventricular assist device and left ventricular assist device recipients was 90% versus 86% (not significant), with shorter heart transplantation waiting times for biventricular assist device recipients (median days, 154 vs 302, P < .001). Overall survival at 1 year was 85% (95% confidence interval, 62-95) versus 86% (95% confidence interval, 64-95) (not significant). The majority of both biventricular assist device and left ventricular assist device recipients could be discharged to home during the heart transplantation waiting time (55% vs 71%, not significant), and complication rates on device were comparable between groups (major stroke 10% vs 10%, not significant). CONCLUSIONS: Planned in advance, the biventricular assist device seems to be a feasible option as bridge to heart transplantation for patients with a high risk of postimplant right ventricular failure. The outcomes for these patients were similar to those observed for contemporary left ventricular assist device recipients, despite those receiving biventricular assist devices being more severely ill.