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K. Karason

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Pertti Suominen

University of Melbourne

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Simon Matskeplishvili

Federico Franchi

Luigi Tritapepe

Università degli Studi "La Sapienza" di Roma

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Papers by K. Karason

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Cardiac Failure Review, 2020

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish... more Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration...

Cardiac Re-Transplantation - A Reasonable Treatment Option in Selected Patients with Severe Graft Failure?

The Journal of Heart and Lung Transplantation, 2020

Purpose: Heart re-transplantation (re-HTx) has been considered controversial due to shortage of d... more Purpose: Heart re-transplantation (re-HTx) has been considered controversial due to shortage of donor organs and suboptimal results. We studied the results of cardiac re-Tx and compared it with primary heart transplantation (HTx) at our center. Methods: A total of 708 heart transplantations were carried out at our center between 1984 and 2017. 21 of those were re-HTx. One patient had been re-transplanted twice and two other patients had their primary transplantation in London before our program started. In a retrospective study, we evaluated pre-operative characteristics, cause of graft-loss, immunology and outcome among patients undergoing cardiac re-Tx and compared them with the primary HTx population. Results: A total of 20 patients (14 male, 5 female) received a second HTx (n=20) or a third HTx (n=1) at Sahlgrenska University Hospital. Mean age at re-HTx was 35 as compared to 45 years for the primary HTx group. Mean donor age in the re-HTx and primary HTx groups was 42 and 37 years, respectively. The primary cardiac diagnosis for re-HTx patients was DCM (n=11), myocarditis (n=3), IHD (n=2), CHD (n=2) and unknown (n=1). The causes of graft failure and re-HTx were acute rejection (n=5), coronary allograft vasculopathy (CAV) (n=5), and unexplained graft failure (n=10). The median time interval between primary and re-Tx was 49 months (range 0-305 months). Patients undergoing re-HTx were more often in need of pre-operative dialysis (37%) as compared with primary HTx (1.5%). Also, the re-HTx group was more often treated with a short-term MCS (37 %; 6 ECMO, 1 BiVAD) than those receiving a primary HTx (19%). The 1-, 5-and 10-year survival rates for re-HTx and primary HTx were 85% (95%CI:60-95) / 58% (95%CI:33-76) / 45% (95%CI:22-66) and 88% (95%CI:86-90) / 80% (95%CI:77-83) / 68% (95%CI:63-71), respectively. Causes of death in the re-Tx group included acute transplant related death (n=1), cardiac death (n=2) and non-cardiac causes (infection/ malignancy, n=3). Conclusion: During a 30-year period, 3% of our HTx population underwent a re-HTx. The most common cause for re-HTx was unexplained graft failure, followed by acute rejection and CAV. Although inferior to primary HTx, cardiac re-HTx offers a reasonable long-term outcome and should therefore be offered to selected patients.

Berlin Heart Excor as Bridge to Heart Transplantation. A Versatile Option in Patients Not Suitable for a Continuous Flow LVAD

The Journal of Heart and Lung Transplantation, 2018

of whom 4 had a major stroke (1 child and 3 adults). Other complications included: drive line inf... more of whom 4 had a major stroke (1 child and 3 adults). Other complications included: drive line infection (n= 7), wound infection/ mediastinitis (n= 2), septicemia (n= 4) and pneumonia (n= 3). Conclusion: The Excor paracorporeal VAD is a versatile device used as BTT in patients not suitable for CF-LVAD. The survival rate was acceptable considering the severity of illness in this patient population and the outcome did not differ between children and adults. However, complications do occur, and Excor treatment continues to be challenged by device related thromboembolism, infections and malfunction due to membrane rupture.

Cell-Free DNA in the Early Course After Heart Transplantation

The Journal of Heart and Lung Transplantation

Multicenter Evaluation of Volumetric Intravascular Ultrasound Early After Heart Transplantation and Long-Term Prognosis

The Journal of Heart and Lung Transplantation

Malignancies before and after Heart Transplantation - A Single-Centre Long-Term Outcome Study

The Journal of Heart and Lung Transplantation, 2021

Purpose Heart transplantation (HTx) has become the standard treatment for patients with end-stage... more Purpose Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. The aim of this study was to report our incidence and long-term outcome of malignancies after HTx. Methods The study is a single centre retrospective study of 664 patients, who underwent HTx at our centre between, 1985-2017. Data were retrieved from the Cancer Registry and the Birth and Death registry, both of which are obligatory national registries managed by the National Board of Health and Welfare. Results In total, 231 malignancies were diagnosed in 138 patients (19.6%). The median follow-up time was 6.9 years (IQR 2.4-13.1). No patient was lost to follow-up. The overall risk of cancer following organ transplantation was 6.1-fold and 2.9-fold when excluding nonmelanoma skin cancer. The three most common malignancies were; nonmelanoma skin cancer, non-Hodgins lymphoma and lung cancer. There was no significant difference (p Conclusion Nineteen percent of patients had experienced a malignancy after almost 7 years of median follow-up after HTx. We have shown an overall risk of cancer to be over 6-fold higher than among the general population, and almost 3-fold higher when non-melanoma skin cancer was excluded, after heart transplantation.

Cell-Free DNA after Heart Transplantation: New Aspects of the Story

The Journal of Heart and Lung Transplantation, 2021

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

International Journal of Cardiology, 2019

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute th... more Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

Associations between Self-Reported Physical Function and Exercise Capacity in De Novo Heart Transplant Recipients

The Journal of Heart and Lung Transplantation, 2019

Purpose: Continuous flow left ventricular assist device (CF-LVAD) support has been associated wit... more Purpose: Continuous flow left ventricular assist device (CF-LVAD) support has been associated with gastrointestinal bleeding (GIB), primarily from arteriovenous malformations or ulcers, and exacerbated by the requirement for anticoagulation. In this report, we explore whether GIB persisted after heart transplant in patients who experienced GIB events while on CF-LVAD support. Methods: We performed a retrospective review of 701 patients who underwent implantation of CF-LVADs from August 2002 through August 2017 at our center, and identified patients who underwent CF-LVAD implantation as a Bridge-to-Transplant, experienced at least one GIB event during CF-LVAD support, and were successfully bridged to heart transplantation. We evaluated the incidence of GIB events in these patients after heart transplantation. Results: A total of 46 heart transplant recipients fit the inclusion criteria. There were a total of 63 total GIB events while on CF-LVAD support. Locations of GIB events included esophagus (N=3), stomach (N=21), duodenum (N=7), jejunum (N=3), small intestine not-otherwise-specified (N=12), colon (N=14), and rectum (N=3). Etiologies included gastritis (N=10), ulcer (N=11), arteriovenous malformation (N=13), angiodysplasia (N=3), polyp (N=2), diverticulosis (N=8), and Mallory Wiess tear (N=2). Mean LVAD support time was 1.4 §1.5 years (65.4 cumulative patientyears). Mean follow-up time after transplantation was 4.0 §3.5 years (183.3 cumulative patient-years after transplantation). There was only 1 GIB event after heart transplantation (events per patient-year: 0.005). The etiology was non-specific acute colitis in a patient who had prior GIB from a gastric ulcer while on LVAD therapy. Time from transplant to GIB event was 3.9 years. The patient was taking aspirin 81mg daily at the time of GIB. Conclusion: GIB during CF-LVAD therapy did not persist after heart transplantation. This may be due to restoration of pulsatile flow. Introduction of a greater degree of pulsatility into LVAD flow technology may improve the incidence of GIB while on CF-LVAD support.

Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 26, 2015

In organ transplanted patients, impaired renal function is of major prognostic importance and inf... more In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population. We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up. The correlations between eGFR and mGFR were only m...

5698Parvovirus B19 in endomyocardial biopsy of patients with idiopathic dilated cardiomyopathy: foe or bystander?

European Heart Journal

Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used... more Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used as a first line mechanical circulatory support (MCS) for patients with fulminant myocarditis (FM). Although PVA-ECMO is suitable for the short-term management of FM, conversion to other forms of MCS such as biventricular assist devices should be considered when long-term management is required. However, little is known about when and how to decide the conversion to other forms of MCS under the consideration of patients' prognosis. We hypothesized that we could predict these patients' outcomes by evaluating the changes of cardiac function and biochemical markers, because cardiac recovery and prevention of end organ damage are cornerstones of successful management of PVA-ECMO. Purpose: The purpose of this study is to develop a prediction model of successful recovery in FM patients supported with PVA-ECMO. Methods: The CHANGE PUMP study was designed as a multicenter retrospective chart review, focused on the data changes during the use of PVA-ECMO in patients with FM. We enrolled 99 patients with FM supported with PVA-ECMO (mean of 52±16 years, female 42%). Patients with critical complications within 24 hours from the PVA-ECMO initiation were excluded. We defined 46 patients who were successfully weaned off PVA-ECMO and discharged from the hospital as the Success group (S-group). The other 53 patients including in-hospital death or requiring conversion to other forms of MCS defined as the Failure group (Fgroup). Serial changes of left ventricular ejection fraction (LVEF) and biochemical markers were obtained from PCPS initiation (0-hr) to 144 hours after. Results: The median run time of PVA-ECMO was 137 hours. Thirty-seven patients underwent cardiopulmonary resuscitation before PVA-ECMO initiation. At the time 0-hr, the S-group had significantly higher LVEF and lower AST0-hr, ALT0-hr, LDH0-hr and Cr0-hr levels than the F-group. However, it was impossible to develop a significant S-group prediction model by using these variables. At the time of 48 hours after the PVA-ECMO initiation (48-hr), LVEF48-hr and changes of LVEF and AST from the 0-hr (LVEF48-hr and AST48-hr, respectively) were detected as independent predictors of the S-group. Finally, we developed the S-group prediction model consisting of the following three variables; S-group probability (%) = 1/[1 + exp-(0.688-0.104*LVEF48-hr-0.143* LVEF48hr + 1.171* AST48-hr)] *100. In logistic regression analyses for the internal validation, the area under the curve of the model was 0.844 (95% CI 0.745-0.944) and the predicted S-group probability and observed S-group proportion were well matched (Figure). Conclusion: Our developing model could predict successful recovery from PVA-ECMO in FM patients at 48-hr. We suggest that clinicians should decide whether to convert to other forms of MCS at 48-hr.

XII CONGRESS OF MEDITERRANEAN SOCIETY OF MYOLOGY Naples, Italy - May 18-20, 2015 Program (Summary)

Acta Myologica, 2015

A Standardized Protocol for Donor-Derived Cell-Free DNA Quantification in the Diagnosis of Allograft Injury

The Journal of Heart and Lung Transplantation

Purpose There is an increasing interest in the use of donor-derived cfDNA (dd-cfDNA) in transplan... more Purpose There is an increasing interest in the use of donor-derived cfDNA (dd-cfDNA) in transplantation for non-invasive diagnosis of allograft injury. We hereby describe a non-commercial routine procedure for dd-cfDNA detection and quantification using digital droplet PCR and target-specific preamplification of a SNP-panel of 35 SNP-assays. The method is based on the difference in genotype between recipients and donors. After establishing our protocol, it has been used in a prospective study following recipients for 12 months after heart transplantation (HTx), and we here briefly describe our protocol. Methods A total of 728 samples from 67 HTx patients have been retrieved and analyzed. The recipients were genotyped preoperatively with respect to the SNP-panel. Upon transplantation, the donor genotype was interrogated with respect to the homozygous alleles found in the recipient. After HTx, blood samples were collected in cell free DNA collection tubes and delivered within the same day to the hospital laboratory. Plasma was separated by centrifugation at 2000g and 16000g, respectively. Isolated plasma was stored at -80C or used immediately for cfDNA extraction. Quality controls were performed by the 4200 Tape Station. The same primers were used for preamplification and downstream PCR. Non-template controls were included in all preamplification steps. The amount of dd-cfDNA was calculated as a fraction of the total cfDNA. Results The variation of extracted cfDNA yield was 10-130 ng/ml plasma. The 50-800 bp sized cfDNA constitutes 90% of the extracted samples, indicating a low background. An average of 2-5 informative SNPS assays for each transplant recipient were used for dd-cfDNA quantification with a detection rate down to 0.01% dd-cfDNA. Elevation of dd-cfDNA was seen not only in conjunction with cellular rejection but also during infection and in episodes of heart failure Conclusion Samples from HTx recipients demonstrated low levels of dd-cfDNA in consecutive samples during optimal treatment in non-eventful cases. Elevation of dd-cfDNA was seen not only during rejection but also in other conditions. This non-invasive method is relatively cheap, enables large sample yields by preamplification, has a fast turn-around time (48 hours) and is thus useful for clinical monitoring of HTx patients. However, it needs to be carefully related to clinical events.

Atrial Natriuretic Peptide in the Prevention of Postoperative Acute Renal Dysfunction in Patients Undergoing Heart Transplantation - An Investigator-Driven, Single-Center, Blinded, Randomized and Placebo-Controlled Trial

The Journal of Heart and Lung Transplantation

Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complicati... more Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complication after heart transplantation (HTx) that is associated with increased morbidity and mortality. When used for treatment of AKI, infusion of atrial natriuretic peptide (ANP) has been shown to increase renal blood flow and glomerular filtration rate (GFR) after complicated cardiac surgery and in cyclosporine-induced AKI after HTx. Furthermore, it was shown that ANP reduced the probability of dialysis in cardiac surgery-associated AKI. The aim of this investigation was to evaluate whether ANP infusion could prevent or mitigate acute renal dysfunction after HTx. Methods After approval of Ethical Review Board and the Swedish Medical Products Agency, 72 adult patients undergoing HTx were included after informed consent. The patients were randomized to receive either ANP or placebo (saline) by a web-based computerized random-number generator. The anesthesia/intensive staff and physicians were blinded to the allocated treatment throughout the entire study. After induction of anesthesia, a continuous intravenous infusion of either ANP (HANP1000®, Daichii Sankyo Propharma, Japan) at a dose of 50 ng/kg/min or the equivalent volume of placebo (saline) was started. The administration of the study drugs continued for five postop days, or until the patient died or treatment with dialysis was started. Inclusion has been completed. Endpoints The primary end-point was measured mGFR at day five. mGFR was assessed by the infusion clearance of 52Cr-EDTA. The difference in mGFR between groups was estimated using intention-to-treat and per-protocol analyses. To detect a 30% higher mGFR in the ANP group, 31 patients per group would be required, assuming a 80% power and a two-sided error of 0.05. To compensate for drop-outs and for the use of nonparametric tests, we included 35 randomised patients per group. Secondary end-points were: the incidence of postoperative AKI (KDIGO criteria), daily postoperative serum creatinine, need for dialysis, intra- and postoperative diuresis, the use of diuretics, length of ICU and hospital stay, ICU mortality and 30-days mortality, length of mechanical ventilation, incidence of hypotension and arrhythmias and inotropic score.

5698Parvovirus B19 in endomyocardial biopsy of patients with idiopathic dilated cardiomyopathy: foe or bystander?

European Heart Journal, Aug 1, 2017

Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used... more Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used as a first line mechanical circulatory support (MCS) for patients with fulminant myocarditis (FM). Although PVA-ECMO is suitable for the short-term management of FM, conversion to other forms of MCS such as biventricular assist devices should be considered when long-term management is required. However, little is known about when and how to decide the conversion to other forms of MCS under the consideration of patients' prognosis. We hypothesized that we could predict these patients' outcomes by evaluating the changes of cardiac function and biochemical markers, because cardiac recovery and prevention of end organ damage are cornerstones of successful management of PVA-ECMO. Purpose: The purpose of this study is to develop a prediction model of successful recovery in FM patients supported with PVA-ECMO. Methods: The CHANGE PUMP study was designed as a multicenter retrospective chart review, focused on the data changes during the use of PVA-ECMO in patients with FM. We enrolled 99 patients with FM supported with PVA-ECMO (mean of 52±16 years, female 42%). Patients with critical complications within 24 hours from the PVA-ECMO initiation were excluded. We defined 46 patients who were successfully weaned off PVA-ECMO and discharged from the hospital as the Success group (S-group). The other 53 patients including in-hospital death or requiring conversion to other forms of MCS defined as the Failure group (Fgroup). Serial changes of left ventricular ejection fraction (LVEF) and biochemical markers were obtained from PCPS initiation (0-hr) to 144 hours after. Results: The median run time of PVA-ECMO was 137 hours. Thirty-seven patients underwent cardiopulmonary resuscitation before PVA-ECMO initiation. At the time 0-hr, the S-group had significantly higher LVEF and lower AST0-hr, ALT0-hr, LDH0-hr and Cr0-hr levels than the F-group. However, it was impossible to develop a significant S-group prediction model by using these variables. At the time of 48 hours after the PVA-ECMO initiation (48-hr), LVEF48-hr and changes of LVEF and AST from the 0-hr (LVEF48-hr and AST48-hr, respectively) were detected as independent predictors of the S-group. Finally, we developed the S-group prediction model consisting of the following three variables; S-group probability (%) = 1/[1 + exp-(0.688-0.104*LVEF48-hr-0.143* LVEF48hr + 1.171* AST48-hr)] *100. In logistic regression analyses for the internal validation, the area under the curve of the model was 0.844 (95% CI 0.745-0.944) and the predicted S-group probability and observed S-group proportion were well matched (Figure). Conclusion: Our developing model could predict successful recovery from PVA-ECMO in FM patients at 48-hr. We suggest that clinicians should decide whether to convert to other forms of MCS at 48-hr.

Clinical Diagnosis and Subtyping of Cardiac Amyloidosis by Mass Spectrometry

The Journal of Heart and Lung Transplantation

PURPOSE Medical treatment for cardiac amyloidosis (CA) is evolving rapidly. Heart transplantation... more PURPOSE Medical treatment for cardiac amyloidosis (CA) is evolving rapidly. Heart transplantation can be a valid option when followed by transplantation of bone marrow or liver, dependent on the type and origin of the amyloid protein. Thus, accurate typing of amyloidosis has implications for treatment, prognosis, and genetic counseling. Although non-invasive diagnostic techniques can type CA, endomyocardial biopsy (EMB) may be needed in the case of equivocal imaging findings or discordant data. We aimed to define the role of mass spectrometry (MS) for diagnosis and subtyping of CA. METHODS Nineteen previously diagnosed CA cases, who underwent EMB at Sahlgrenska University Hospital (SU), Gothenburg, between the beginning 1990s and 2016, were selected. MS analysis, modified from was conducted on duplicate samples from myocardial tissue for each case included.1 Clinical features and diagnoses were used as gold standard and compared to the MS findings. RESULTS Clinical diagnosis and the MS analysis agreed in 14 cases (73.7 %); in 3/19 (15.8 %) diagnosis was unclear or discordant (Fig.1). MS analysis revealed that transthyretin (TTR) amyloidosis was the most abundant amyloid protein in the samples examined (9/19; 47.3 %), whereas the AA subtype only occurred in 1 case (5.2 %). The AL κ type amyloidosis occurred in 3 cases (15.8 %), and AL λ type in six cases (31.6 %). These results strongly correlated with the clinical features in all patients. Clinical diagnosis could not be retrieved from the medical records in 2 cases (10.4 %). Additional 20 patients with clinical CA are presently under study. CONCLUSION MS analysis of a small amount of endomyocardial tissue can be used to subtype CA with a high diagnostic validity. The method differentiated between TTR, SAA and Ig light chain amyloidosis. AL κ and AL λ identities correlated to those found in serum and urine electrophoreses. MS can therefore be of use to subtype CA for cases in which clinical findings are inconclusive. 1) Brambilla F et al. Blood. 2012 Feb 23;119(8):1844-7.

Benefits of High-Intensity Interval Training in a Young and in an Older De Novo Heart Transplant Recipient- Cases from the HITTS Study

The Journal of Heart and Lung Transplantation

PURPOSE High-intensity interval training (HIT) is an effective method to increase exercise capaci... more PURPOSE High-intensity interval training (HIT) is an effective method to increase exercise capacity in de novo heart transplant recipients, as shown in the recently published HITTS study (High-intensity Interval Training in de novo Heart Transplant recipients in Scandinavia). We were interested to scrutinize the potential effect of HIT in different age categories. The main effects of HIT in one young and one older medically stable de novo heart transplant recipients are reported. METHODS The HITTS study is a randomized controlled study comparing HIT versus moderate intensity continuous training (MICT) in de novo heart transplant recipients (mean 11 weeks after heart transplantation). Eighty-one participants were randomized (1:1) to 9 months of HIT or MICT. The primary endpoint was the change in VO2peak. Secondary endpoints included: Heart rate response, muscle strength and self-reported physical function measured by the Short-Form-36. One of the youngest and one of the oldest participants with the highest changes in VO2peak in the HIT intervention group were selected for this case report. RESULTS The youngest male (< 25 years old) increased his VO2peak with 15.3 mL/kg/min from baseline to follow-up (from 23.5 to 38.8 mL/kg/min), while the older male (> 55 years old) increased his VO2peak with 12.6 mL/kg/min (from 15.6 to 28.3 mL/kg/min). Muscle strength, heart rate response, O2 pulse and self-reported physical function also increased substantially (Table). The young heart transplant recipient completed 51 exercise sessions whereas the older heart transplant recipient completed 72 sessions. CONCLUSION Both the young and the older de novo heart transplant recipient increased their VO2peak with at least 4 METS (> 12 mL/kg/min) after a 9-month long HIT intervention. The results show that both young and older individuals can derive substantial benefit from HIT soon after heart transplantation.

Patient Outcomes after Heart Transplantation in Sweden between 1988 and 2017: Continuous Improvement in Survival

The Journal of Heart and Lung Transplantation

PURPOSE To investigate the survival of heart transplant (HTx) recipients during different time pe... more PURPOSE To investigate the survival of heart transplant (HTx) recipients during different time periods in Sweden. We hypothesized that the survival for HTx recipients has improved following advancements in the management of these patients. METHODS Data was obtained through the database of the organ exchange organization Scandiatransplant. All patients who underwent HTx in Sweden between Jan 1988 and Dec 2017 were included. Patients were divided into five cohorts of six-year periods each. RESULTS A total of 1137 HTx recipients were included. Main causes of transplantation were dilated cardiomyopathy (44 %) and ischemic heart disease (18 %). Retransplantation constituted a small portion of the overall total (2 %). The cohorts were similar in terms of age and gender, while later cohorts had higher BMI, lower GFR and longer ischemia time (Tab. 1). The later cohorts received organs from older donors (Tab. 1). The amount of heart transplantations performed in Sweden has increased with time (Tab. 1). Log-rank test comparing the survival curves was able to show improved survival during later eras (Fig. 1). CONCLUSION Survival among HTx recipients has significantly improved in Sweden over time, despite less favorable recipients and donor characteristics. This was related to both reduced postoperative mortality and also improved long-time survival.

P1361 Loading conditions might mimic right ventricular longitudinal dysfunction in patients with chronic left heart disease and forward failure

European Heart Journal - Cardiovascular Imaging

Background and aim Right ventricular failure (RVF) in patients with chronic left heart disease (L... more Background and aim Right ventricular failure (RVF) in patients with chronic left heart disease (LHD) has important prognostic implications. RV longitudinal function parameters (tricuspid annular plane systolic excursion, TAPSE; peak systolic longitudinal strain, RV-Str; tricuspid annulus systolic velocity, TAPSm) are today commonly used to define RV dysfunction. In the present study we hypothesized that longitudinal RV dysfunction (LDF) might be due to loading conditions and not necessarily RV dysfunction. Methods We retrospectively included 66 patients with LHD (age 52 ± 13 years, males 79%) that underwent right heart catheterization (RHC), ergospirometry (n = 47) and echocardiography (Echo) within 48 hours. Patients were divided into three groups from Echo data: normal RV function (TAPSE ≥17 mm + normal central venous pressure (CVP) from collapsibility of cava inferior, n = 18); LDF (TAPSE < 17 mm + normal CVP, n = 22) and RVF (CVP≥10 mmHg, n = 26). Results Patients with RVF ha...

P899 Reduced right ventricular longitudinal function in patients with chronic left ventricular disease can be due to left ventricular forward failure and not right ventricular dysfunction

European Heart Journal - Cardiovascular Imaging

Background and aim The occurrence of right ventricular failure (RVF) in patients with chronic lef... more Background and aim The occurrence of right ventricular failure (RVF) in patients with chronic left heart disease (LHD) has important therapeutic and prognostic consequences. Echocardiography (Echo) parameters describing the RV longitudinal function (tricuspid annular plane systolic excursion, TAPSE; peak systolic free wall longitudinal strain, RV-Str; tricuspid annulus peak systolic velocity, TAPSm) are today commonly used to define RV dysfunction. In the present study we hypothesised that these parameters are load dependent. Methods We retrospectively included 66 patients with LHD (age 52 ± 13 years, males 79%) that underwent right heart catheterization (RHC) and Echo within 48 hours. RHC was performed as part of diagnostic- or pre-transplant work-up. Fifty-six patients (85%) had left ventricular ejection fraction < 40%. From RHC data the patients were divided into three groups: Patients with RV decompensation and increased right atrial pressure (RAP) ≥10 mmHg (iRAP, n = 21), wi...

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Cardiac Failure Review, 2020

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish... more Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration...

Cardiac Re-Transplantation - A Reasonable Treatment Option in Selected Patients with Severe Graft Failure?

The Journal of Heart and Lung Transplantation, 2020

Purpose: Heart re-transplantation (re-HTx) has been considered controversial due to shortage of d... more Purpose: Heart re-transplantation (re-HTx) has been considered controversial due to shortage of donor organs and suboptimal results. We studied the results of cardiac re-Tx and compared it with primary heart transplantation (HTx) at our center. Methods: A total of 708 heart transplantations were carried out at our center between 1984 and 2017. 21 of those were re-HTx. One patient had been re-transplanted twice and two other patients had their primary transplantation in London before our program started. In a retrospective study, we evaluated pre-operative characteristics, cause of graft-loss, immunology and outcome among patients undergoing cardiac re-Tx and compared them with the primary HTx population. Results: A total of 20 patients (14 male, 5 female) received a second HTx (n=20) or a third HTx (n=1) at Sahlgrenska University Hospital. Mean age at re-HTx was 35 as compared to 45 years for the primary HTx group. Mean donor age in the re-HTx and primary HTx groups was 42 and 37 years, respectively. The primary cardiac diagnosis for re-HTx patients was DCM (n=11), myocarditis (n=3), IHD (n=2), CHD (n=2) and unknown (n=1). The causes of graft failure and re-HTx were acute rejection (n=5), coronary allograft vasculopathy (CAV) (n=5), and unexplained graft failure (n=10). The median time interval between primary and re-Tx was 49 months (range 0-305 months). Patients undergoing re-HTx were more often in need of pre-operative dialysis (37%) as compared with primary HTx (1.5%). Also, the re-HTx group was more often treated with a short-term MCS (37 %; 6 ECMO, 1 BiVAD) than those receiving a primary HTx (19%). The 1-, 5-and 10-year survival rates for re-HTx and primary HTx were 85% (95%CI:60-95) / 58% (95%CI:33-76) / 45% (95%CI:22-66) and 88% (95%CI:86-90) / 80% (95%CI:77-83) / 68% (95%CI:63-71), respectively. Causes of death in the re-Tx group included acute transplant related death (n=1), cardiac death (n=2) and non-cardiac causes (infection/ malignancy, n=3). Conclusion: During a 30-year period, 3% of our HTx population underwent a re-HTx. The most common cause for re-HTx was unexplained graft failure, followed by acute rejection and CAV. Although inferior to primary HTx, cardiac re-HTx offers a reasonable long-term outcome and should therefore be offered to selected patients.

Berlin Heart Excor as Bridge to Heart Transplantation. A Versatile Option in Patients Not Suitable for a Continuous Flow LVAD

The Journal of Heart and Lung Transplantation, 2018

of whom 4 had a major stroke (1 child and 3 adults). Other complications included: drive line inf... more of whom 4 had a major stroke (1 child and 3 adults). Other complications included: drive line infection (n= 7), wound infection/ mediastinitis (n= 2), septicemia (n= 4) and pneumonia (n= 3). Conclusion: The Excor paracorporeal VAD is a versatile device used as BTT in patients not suitable for CF-LVAD. The survival rate was acceptable considering the severity of illness in this patient population and the outcome did not differ between children and adults. However, complications do occur, and Excor treatment continues to be challenged by device related thromboembolism, infections and malfunction due to membrane rupture.

Cell-Free DNA in the Early Course After Heart Transplantation

The Journal of Heart and Lung Transplantation

Multicenter Evaluation of Volumetric Intravascular Ultrasound Early After Heart Transplantation and Long-Term Prognosis

The Journal of Heart and Lung Transplantation

Malignancies before and after Heart Transplantation - A Single-Centre Long-Term Outcome Study

The Journal of Heart and Lung Transplantation, 2021

Purpose Heart transplantation (HTx) has become the standard treatment for patients with end-stage... more Purpose Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. The aim of this study was to report our incidence and long-term outcome of malignancies after HTx. Methods The study is a single centre retrospective study of 664 patients, who underwent HTx at our centre between, 1985-2017. Data were retrieved from the Cancer Registry and the Birth and Death registry, both of which are obligatory national registries managed by the National Board of Health and Welfare. Results In total, 231 malignancies were diagnosed in 138 patients (19.6%). The median follow-up time was 6.9 years (IQR 2.4-13.1). No patient was lost to follow-up. The overall risk of cancer following organ transplantation was 6.1-fold and 2.9-fold when excluding nonmelanoma skin cancer. The three most common malignancies were; nonmelanoma skin cancer, non-Hodgins lymphoma and lung cancer. There was no significant difference (p Conclusion Nineteen percent of patients had experienced a malignancy after almost 7 years of median follow-up after HTx. We have shown an overall risk of cancer to be over 6-fold higher than among the general population, and almost 3-fold higher when non-melanoma skin cancer was excluded, after heart transplantation.

Cell-Free DNA after Heart Transplantation: New Aspects of the Story

The Journal of Heart and Lung Transplantation, 2021

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

International Journal of Cardiology, 2019

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute th... more Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

Associations between Self-Reported Physical Function and Exercise Capacity in De Novo Heart Transplant Recipients

The Journal of Heart and Lung Transplantation, 2019

Purpose: Continuous flow left ventricular assist device (CF-LVAD) support has been associated wit... more Purpose: Continuous flow left ventricular assist device (CF-LVAD) support has been associated with gastrointestinal bleeding (GIB), primarily from arteriovenous malformations or ulcers, and exacerbated by the requirement for anticoagulation. In this report, we explore whether GIB persisted after heart transplant in patients who experienced GIB events while on CF-LVAD support. Methods: We performed a retrospective review of 701 patients who underwent implantation of CF-LVADs from August 2002 through August 2017 at our center, and identified patients who underwent CF-LVAD implantation as a Bridge-to-Transplant, experienced at least one GIB event during CF-LVAD support, and were successfully bridged to heart transplantation. We evaluated the incidence of GIB events in these patients after heart transplantation. Results: A total of 46 heart transplant recipients fit the inclusion criteria. There were a total of 63 total GIB events while on CF-LVAD support. Locations of GIB events included esophagus (N=3), stomach (N=21), duodenum (N=7), jejunum (N=3), small intestine not-otherwise-specified (N=12), colon (N=14), and rectum (N=3). Etiologies included gastritis (N=10), ulcer (N=11), arteriovenous malformation (N=13), angiodysplasia (N=3), polyp (N=2), diverticulosis (N=8), and Mallory Wiess tear (N=2). Mean LVAD support time was 1.4 §1.5 years (65.4 cumulative patientyears). Mean follow-up time after transplantation was 4.0 §3.5 years (183.3 cumulative patient-years after transplantation). There was only 1 GIB event after heart transplantation (events per patient-year: 0.005). The etiology was non-specific acute colitis in a patient who had prior GIB from a gastric ulcer while on LVAD therapy. Time from transplant to GIB event was 3.9 years. The patient was taking aspirin 81mg daily at the time of GIB. Conclusion: GIB during CF-LVAD therapy did not persist after heart transplantation. This may be due to restoration of pulsatile flow. Introduction of a greater degree of pulsatility into LVAD flow technology may improve the incidence of GIB while on CF-LVAD support.

Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 26, 2015

In organ transplanted patients, impaired renal function is of major prognostic importance and inf... more In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population. We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up. The correlations between eGFR and mGFR were only m...

5698Parvovirus B19 in endomyocardial biopsy of patients with idiopathic dilated cardiomyopathy: foe or bystander?

European Heart Journal

Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used... more Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used as a first line mechanical circulatory support (MCS) for patients with fulminant myocarditis (FM). Although PVA-ECMO is suitable for the short-term management of FM, conversion to other forms of MCS such as biventricular assist devices should be considered when long-term management is required. However, little is known about when and how to decide the conversion to other forms of MCS under the consideration of patients' prognosis. We hypothesized that we could predict these patients' outcomes by evaluating the changes of cardiac function and biochemical markers, because cardiac recovery and prevention of end organ damage are cornerstones of successful management of PVA-ECMO. Purpose: The purpose of this study is to develop a prediction model of successful recovery in FM patients supported with PVA-ECMO. Methods: The CHANGE PUMP study was designed as a multicenter retrospective chart review, focused on the data changes during the use of PVA-ECMO in patients with FM. We enrolled 99 patients with FM supported with PVA-ECMO (mean of 52±16 years, female 42%). Patients with critical complications within 24 hours from the PVA-ECMO initiation were excluded. We defined 46 patients who were successfully weaned off PVA-ECMO and discharged from the hospital as the Success group (S-group). The other 53 patients including in-hospital death or requiring conversion to other forms of MCS defined as the Failure group (Fgroup). Serial changes of left ventricular ejection fraction (LVEF) and biochemical markers were obtained from PCPS initiation (0-hr) to 144 hours after. Results: The median run time of PVA-ECMO was 137 hours. Thirty-seven patients underwent cardiopulmonary resuscitation before PVA-ECMO initiation. At the time 0-hr, the S-group had significantly higher LVEF and lower AST0-hr, ALT0-hr, LDH0-hr and Cr0-hr levels than the F-group. However, it was impossible to develop a significant S-group prediction model by using these variables. At the time of 48 hours after the PVA-ECMO initiation (48-hr), LVEF48-hr and changes of LVEF and AST from the 0-hr (LVEF48-hr and AST48-hr, respectively) were detected as independent predictors of the S-group. Finally, we developed the S-group prediction model consisting of the following three variables; S-group probability (%) = 1/[1 + exp-(0.688-0.104*LVEF48-hr-0.143* LVEF48hr + 1.171* AST48-hr)] *100. In logistic regression analyses for the internal validation, the area under the curve of the model was 0.844 (95% CI 0.745-0.944) and the predicted S-group probability and observed S-group proportion were well matched (Figure). Conclusion: Our developing model could predict successful recovery from PVA-ECMO in FM patients at 48-hr. We suggest that clinicians should decide whether to convert to other forms of MCS at 48-hr.

XII CONGRESS OF MEDITERRANEAN SOCIETY OF MYOLOGY Naples, Italy - May 18-20, 2015 Program (Summary)

Acta Myologica, 2015

A Standardized Protocol for Donor-Derived Cell-Free DNA Quantification in the Diagnosis of Allograft Injury

The Journal of Heart and Lung Transplantation

Purpose There is an increasing interest in the use of donor-derived cfDNA (dd-cfDNA) in transplan... more Purpose There is an increasing interest in the use of donor-derived cfDNA (dd-cfDNA) in transplantation for non-invasive diagnosis of allograft injury. We hereby describe a non-commercial routine procedure for dd-cfDNA detection and quantification using digital droplet PCR and target-specific preamplification of a SNP-panel of 35 SNP-assays. The method is based on the difference in genotype between recipients and donors. After establishing our protocol, it has been used in a prospective study following recipients for 12 months after heart transplantation (HTx), and we here briefly describe our protocol. Methods A total of 728 samples from 67 HTx patients have been retrieved and analyzed. The recipients were genotyped preoperatively with respect to the SNP-panel. Upon transplantation, the donor genotype was interrogated with respect to the homozygous alleles found in the recipient. After HTx, blood samples were collected in cell free DNA collection tubes and delivered within the same day to the hospital laboratory. Plasma was separated by centrifugation at 2000g and 16000g, respectively. Isolated plasma was stored at -80C or used immediately for cfDNA extraction. Quality controls were performed by the 4200 Tape Station. The same primers were used for preamplification and downstream PCR. Non-template controls were included in all preamplification steps. The amount of dd-cfDNA was calculated as a fraction of the total cfDNA. Results The variation of extracted cfDNA yield was 10-130 ng/ml plasma. The 50-800 bp sized cfDNA constitutes 90% of the extracted samples, indicating a low background. An average of 2-5 informative SNPS assays for each transplant recipient were used for dd-cfDNA quantification with a detection rate down to 0.01% dd-cfDNA. Elevation of dd-cfDNA was seen not only in conjunction with cellular rejection but also during infection and in episodes of heart failure Conclusion Samples from HTx recipients demonstrated low levels of dd-cfDNA in consecutive samples during optimal treatment in non-eventful cases. Elevation of dd-cfDNA was seen not only during rejection but also in other conditions. This non-invasive method is relatively cheap, enables large sample yields by preamplification, has a fast turn-around time (48 hours) and is thus useful for clinical monitoring of HTx patients. However, it needs to be carefully related to clinical events.

Atrial Natriuretic Peptide in the Prevention of Postoperative Acute Renal Dysfunction in Patients Undergoing Heart Transplantation - An Investigator-Driven, Single-Center, Blinded, Randomized and Placebo-Controlled Trial

The Journal of Heart and Lung Transplantation

Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complicati... more Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complication after heart transplantation (HTx) that is associated with increased morbidity and mortality. When used for treatment of AKI, infusion of atrial natriuretic peptide (ANP) has been shown to increase renal blood flow and glomerular filtration rate (GFR) after complicated cardiac surgery and in cyclosporine-induced AKI after HTx. Furthermore, it was shown that ANP reduced the probability of dialysis in cardiac surgery-associated AKI. The aim of this investigation was to evaluate whether ANP infusion could prevent or mitigate acute renal dysfunction after HTx. Methods After approval of Ethical Review Board and the Swedish Medical Products Agency, 72 adult patients undergoing HTx were included after informed consent. The patients were randomized to receive either ANP or placebo (saline) by a web-based computerized random-number generator. The anesthesia/intensive staff and physicians were blinded to the allocated treatment throughout the entire study. After induction of anesthesia, a continuous intravenous infusion of either ANP (HANP1000®, Daichii Sankyo Propharma, Japan) at a dose of 50 ng/kg/min or the equivalent volume of placebo (saline) was started. The administration of the study drugs continued for five postop days, or until the patient died or treatment with dialysis was started. Inclusion has been completed. Endpoints The primary end-point was measured mGFR at day five. mGFR was assessed by the infusion clearance of 52Cr-EDTA. The difference in mGFR between groups was estimated using intention-to-treat and per-protocol analyses. To detect a 30% higher mGFR in the ANP group, 31 patients per group would be required, assuming a 80% power and a two-sided error of 0.05. To compensate for drop-outs and for the use of nonparametric tests, we included 35 randomised patients per group. Secondary end-points were: the incidence of postoperative AKI (KDIGO criteria), daily postoperative serum creatinine, need for dialysis, intra- and postoperative diuresis, the use of diuretics, length of ICU and hospital stay, ICU mortality and 30-days mortality, length of mechanical ventilation, incidence of hypotension and arrhythmias and inotropic score.

5698Parvovirus B19 in endomyocardial biopsy of patients with idiopathic dilated cardiomyopathy: foe or bystander?

European Heart Journal, Aug 1, 2017

Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used... more Background: Percutaneous veno-atrial extracorporeal membrane oxygenation (PVA-ECMO) is often used as a first line mechanical circulatory support (MCS) for patients with fulminant myocarditis (FM). Although PVA-ECMO is suitable for the short-term management of FM, conversion to other forms of MCS such as biventricular assist devices should be considered when long-term management is required. However, little is known about when and how to decide the conversion to other forms of MCS under the consideration of patients' prognosis. We hypothesized that we could predict these patients' outcomes by evaluating the changes of cardiac function and biochemical markers, because cardiac recovery and prevention of end organ damage are cornerstones of successful management of PVA-ECMO. Purpose: The purpose of this study is to develop a prediction model of successful recovery in FM patients supported with PVA-ECMO. Methods: The CHANGE PUMP study was designed as a multicenter retrospective chart review, focused on the data changes during the use of PVA-ECMO in patients with FM. We enrolled 99 patients with FM supported with PVA-ECMO (mean of 52±16 years, female 42%). Patients with critical complications within 24 hours from the PVA-ECMO initiation were excluded. We defined 46 patients who were successfully weaned off PVA-ECMO and discharged from the hospital as the Success group (S-group). The other 53 patients including in-hospital death or requiring conversion to other forms of MCS defined as the Failure group (Fgroup). Serial changes of left ventricular ejection fraction (LVEF) and biochemical markers were obtained from PCPS initiation (0-hr) to 144 hours after. Results: The median run time of PVA-ECMO was 137 hours. Thirty-seven patients underwent cardiopulmonary resuscitation before PVA-ECMO initiation. At the time 0-hr, the S-group had significantly higher LVEF and lower AST0-hr, ALT0-hr, LDH0-hr and Cr0-hr levels than the F-group. However, it was impossible to develop a significant S-group prediction model by using these variables. At the time of 48 hours after the PVA-ECMO initiation (48-hr), LVEF48-hr and changes of LVEF and AST from the 0-hr (LVEF48-hr and AST48-hr, respectively) were detected as independent predictors of the S-group. Finally, we developed the S-group prediction model consisting of the following three variables; S-group probability (%) = 1/[1 + exp-(0.688-0.104*LVEF48-hr-0.143* LVEF48hr + 1.171* AST48-hr)] *100. In logistic regression analyses for the internal validation, the area under the curve of the model was 0.844 (95% CI 0.745-0.944) and the predicted S-group probability and observed S-group proportion were well matched (Figure). Conclusion: Our developing model could predict successful recovery from PVA-ECMO in FM patients at 48-hr. We suggest that clinicians should decide whether to convert to other forms of MCS at 48-hr.

Clinical Diagnosis and Subtyping of Cardiac Amyloidosis by Mass Spectrometry

The Journal of Heart and Lung Transplantation

PURPOSE Medical treatment for cardiac amyloidosis (CA) is evolving rapidly. Heart transplantation... more PURPOSE Medical treatment for cardiac amyloidosis (CA) is evolving rapidly. Heart transplantation can be a valid option when followed by transplantation of bone marrow or liver, dependent on the type and origin of the amyloid protein. Thus, accurate typing of amyloidosis has implications for treatment, prognosis, and genetic counseling. Although non-invasive diagnostic techniques can type CA, endomyocardial biopsy (EMB) may be needed in the case of equivocal imaging findings or discordant data. We aimed to define the role of mass spectrometry (MS) for diagnosis and subtyping of CA. METHODS Nineteen previously diagnosed CA cases, who underwent EMB at Sahlgrenska University Hospital (SU), Gothenburg, between the beginning 1990s and 2016, were selected. MS analysis, modified from was conducted on duplicate samples from myocardial tissue for each case included.1 Clinical features and diagnoses were used as gold standard and compared to the MS findings. RESULTS Clinical diagnosis and the MS analysis agreed in 14 cases (73.7 %); in 3/19 (15.8 %) diagnosis was unclear or discordant (Fig.1). MS analysis revealed that transthyretin (TTR) amyloidosis was the most abundant amyloid protein in the samples examined (9/19; 47.3 %), whereas the AA subtype only occurred in 1 case (5.2 %). The AL κ type amyloidosis occurred in 3 cases (15.8 %), and AL λ type in six cases (31.6 %). These results strongly correlated with the clinical features in all patients. Clinical diagnosis could not be retrieved from the medical records in 2 cases (10.4 %). Additional 20 patients with clinical CA are presently under study. CONCLUSION MS analysis of a small amount of endomyocardial tissue can be used to subtype CA with a high diagnostic validity. The method differentiated between TTR, SAA and Ig light chain amyloidosis. AL κ and AL λ identities correlated to those found in serum and urine electrophoreses. MS can therefore be of use to subtype CA for cases in which clinical findings are inconclusive. 1) Brambilla F et al. Blood. 2012 Feb 23;119(8):1844-7.

Benefits of High-Intensity Interval Training in a Young and in an Older De Novo Heart Transplant Recipient- Cases from the HITTS Study

The Journal of Heart and Lung Transplantation

PURPOSE High-intensity interval training (HIT) is an effective method to increase exercise capaci... more PURPOSE High-intensity interval training (HIT) is an effective method to increase exercise capacity in de novo heart transplant recipients, as shown in the recently published HITTS study (High-intensity Interval Training in de novo Heart Transplant recipients in Scandinavia). We were interested to scrutinize the potential effect of HIT in different age categories. The main effects of HIT in one young and one older medically stable de novo heart transplant recipients are reported. METHODS The HITTS study is a randomized controlled study comparing HIT versus moderate intensity continuous training (MICT) in de novo heart transplant recipients (mean 11 weeks after heart transplantation). Eighty-one participants were randomized (1:1) to 9 months of HIT or MICT. The primary endpoint was the change in VO2peak. Secondary endpoints included: Heart rate response, muscle strength and self-reported physical function measured by the Short-Form-36. One of the youngest and one of the oldest participants with the highest changes in VO2peak in the HIT intervention group were selected for this case report. RESULTS The youngest male (< 25 years old) increased his VO2peak with 15.3 mL/kg/min from baseline to follow-up (from 23.5 to 38.8 mL/kg/min), while the older male (> 55 years old) increased his VO2peak with 12.6 mL/kg/min (from 15.6 to 28.3 mL/kg/min). Muscle strength, heart rate response, O2 pulse and self-reported physical function also increased substantially (Table). The young heart transplant recipient completed 51 exercise sessions whereas the older heart transplant recipient completed 72 sessions. CONCLUSION Both the young and the older de novo heart transplant recipient increased their VO2peak with at least 4 METS (> 12 mL/kg/min) after a 9-month long HIT intervention. The results show that both young and older individuals can derive substantial benefit from HIT soon after heart transplantation.

Patient Outcomes after Heart Transplantation in Sweden between 1988 and 2017: Continuous Improvement in Survival

The Journal of Heart and Lung Transplantation

PURPOSE To investigate the survival of heart transplant (HTx) recipients during different time pe... more PURPOSE To investigate the survival of heart transplant (HTx) recipients during different time periods in Sweden. We hypothesized that the survival for HTx recipients has improved following advancements in the management of these patients. METHODS Data was obtained through the database of the organ exchange organization Scandiatransplant. All patients who underwent HTx in Sweden between Jan 1988 and Dec 2017 were included. Patients were divided into five cohorts of six-year periods each. RESULTS A total of 1137 HTx recipients were included. Main causes of transplantation were dilated cardiomyopathy (44 %) and ischemic heart disease (18 %). Retransplantation constituted a small portion of the overall total (2 %). The cohorts were similar in terms of age and gender, while later cohorts had higher BMI, lower GFR and longer ischemia time (Tab. 1). The later cohorts received organs from older donors (Tab. 1). The amount of heart transplantations performed in Sweden has increased with time (Tab. 1). Log-rank test comparing the survival curves was able to show improved survival during later eras (Fig. 1). CONCLUSION Survival among HTx recipients has significantly improved in Sweden over time, despite less favorable recipients and donor characteristics. This was related to both reduced postoperative mortality and also improved long-time survival.

P1361 Loading conditions might mimic right ventricular longitudinal dysfunction in patients with chronic left heart disease and forward failure

European Heart Journal - Cardiovascular Imaging

Background and aim Right ventricular failure (RVF) in patients with chronic left heart disease (L... more Background and aim Right ventricular failure (RVF) in patients with chronic left heart disease (LHD) has important prognostic implications. RV longitudinal function parameters (tricuspid annular plane systolic excursion, TAPSE; peak systolic longitudinal strain, RV-Str; tricuspid annulus systolic velocity, TAPSm) are today commonly used to define RV dysfunction. In the present study we hypothesized that longitudinal RV dysfunction (LDF) might be due to loading conditions and not necessarily RV dysfunction. Methods We retrospectively included 66 patients with LHD (age 52 ± 13 years, males 79%) that underwent right heart catheterization (RHC), ergospirometry (n = 47) and echocardiography (Echo) within 48 hours. Patients were divided into three groups from Echo data: normal RV function (TAPSE ≥17 mm + normal central venous pressure (CVP) from collapsibility of cava inferior, n = 18); LDF (TAPSE < 17 mm + normal CVP, n = 22) and RVF (CVP≥10 mmHg, n = 26). Results Patients with RVF ha...

P899 Reduced right ventricular longitudinal function in patients with chronic left ventricular disease can be due to left ventricular forward failure and not right ventricular dysfunction

European Heart Journal - Cardiovascular Imaging

Background and aim The occurrence of right ventricular failure (RVF) in patients with chronic lef... more Background and aim The occurrence of right ventricular failure (RVF) in patients with chronic left heart disease (LHD) has important therapeutic and prognostic consequences. Echocardiography (Echo) parameters describing the RV longitudinal function (tricuspid annular plane systolic excursion, TAPSE; peak systolic free wall longitudinal strain, RV-Str; tricuspid annulus peak systolic velocity, TAPSm) are today commonly used to define RV dysfunction. In the present study we hypothesised that these parameters are load dependent. Methods We retrospectively included 66 patients with LHD (age 52 ± 13 years, males 79%) that underwent right heart catheterization (RHC) and Echo within 48 hours. RHC was performed as part of diagnostic- or pre-transplant work-up. Fifty-six patients (85%) had left ventricular ejection fraction < 40%. From RHC data the patients were divided into three groups: Patients with RV decompensation and increased right atrial pressure (RAP) ≥10 mmHg (iRAP, n = 21), wi...