Short-term outcomes after heart transplantation using donor hearts preserved with ex vivo perfusion.

The standard Conventional Cold Storage (CCS) during heart transplantation procurement is associated with time-dependent ischemic injury to the graft, which is a significant independent risk factor for post-transplant early morbidity and mortality - especially when cold ischemic time exceeds four hours. Since 2018, Rigshospitalet (Copenhagen, Denmark) has been utilising ex vivo perfusion (Organ Care System, OCS) in selected cases. The objective of this study was to compare the short-term clinical outcomes of patients transplanted with OCS compared to CCS. Methods: This retrospective single-centre study was based on consecutive patients undergoing a heart transplant between January 2018 and April 2021. Patients were selected for the OCS group when the cold ischemic time was expected to exceed four hours. The primary outcome measure was six-month event-free survival. Results: In total, 48 patients were included in the study; nine were transplanted with an OCS heart. The two groups had no significant differences in baseline characteristics. Six-month event-free survival was 77.8% [95% CI: 54.9-100%] in the OCS group and 79.5% [95% CI: 67.8-93.2%] in the CCS group (p = 0.91). While the OCS group had a median out-of-body time that was 183 min longer (p < 0.0001), the cold ischemic time was reduced by 51 min (p = 0.007). Conclusion: In a Scandinavian setting, our data confirms that utilising OCS in heart procurement allows for a longer out-of-body time and a reduced cold ischemic time without negatively affecting safety or early post-transplant outcomes.

Five-Year Clinical and Echocardiographic Outcomes From the NOTION Randomized Clinical Trial in Patients at Lower Surgical Risk.

BACKGROUND: The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years. METHODS: Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria. RESULTS: Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test P=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm2 versus 1.2 cm2, P<0.001) with a lower mean transprosthetic gradient (8.2 mm Hg versus 13.7 mm Hg, P<0.001), both unchanged over time. More TAVR patients had moderate/severe total aortic regurgitation (8.2% versus 0.0%, P<0.001) and a new pacemaker (43.7% versus 8.7%, P<0.001). Four patients had prosthetic reintervention and no difference was found for functional outcomes. CONCLUSIONS: These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01057173.

Outcomes and hospital admissions during long-term support with a HeartMate II.

OBJECTIVES: Continuous-flow left ventricular assist devices like the HeartMate II (HMII) improves survival in severe heart failure but little is known about the incidence and causes of hospitalizations during long-term support which was evaluated in this study. DESIGN: Observational follow-up study comprising all patients who received a HMII at our institution either as bridge-to-transplantation (BTT) or destination therapy (DT). All patients were followed from HMII implantation to transplantation, device explantation, death, or May 2015. RESULTS: The HMII was implanted in 66(44 BTT, 22 DT) patients with a median (range) duration of support since implantation of 329(2-2707) days with 260(2-1080) days in the BTT group and 608(6-2707) days in the DT group. Thirty-day mortality was 12% and one-year survival 76%, comparable for DT and BTT. Among 56 (19 DT and 37 BTT) patients discharged alive with a HMII there were 161 hospital readmissions during a follow-up of 336(37-2682) days corresponding to a hospitalization rate of 1.3(0-19) per patient year and with a length of stay of 5(2-72) days per admission. Most frequent cause of readmission was infections (29%). A history of atrial fibrillation was the only independent factor associated with increased readmission rates. CONCLUSIONS: Our single-center study demonstrated encouraging survival following HMII implantation. Hospital readmissions were frequent, mostly of short duration, mainly due to infections and increased in patients with atrial fibrillation.

Driveline infections in patients supported with a HeartMate II: incidence, aetiology and outcome.

OBJECTIVES: To investigate the incidence and outcome of driveline infections in patients supported with a continuous flow left ventricular assist device (HeartMate II (HMII)) and to study the microbiological aetiology. DESIGN: Retrospective analysis of 31 patients who received an implantation of a HMII. Follow-up was from implantation to either device explantation, death or closure of the study. Clinical signs of infections were divided into superficial, deep or systemic and compared to culture and gram stain, the clinical course and infectious parameters. RESULTS: The incidence of driveline infections was 1.65 episodes per patient per year. Staphylococcus aureus and Escherichia coli were the most common bacterial aetiology. More than two weeks of treatment was required in 81% of the patients. In terms of detecting superficial driveline infections, leucocyte count demonstrated a sensitivity of 27% and C-reactive protein (CRP) a sensitivity of 28%. In 22 cases of driveline infections plasma pro-calcitonin was found to be normal. CONCLUSION: Driveline infections are common in HMII recipients but primarily remain superficial and are reasonably easy to manage. Infectious agents mostly originate from the skin and gastrointestinal tract. Blood biomarkers did not appear to be helpful in detecting driveline infections.

Promising results after percutaneous mitral valve repair.

INTRODUCTION: Mitral valve regurgitation (MR) is the secondmost frequent valve disease in Europe. Untreated MR causes considerable morbidity and mortality. In the elderly, as many as half of these patients are denied surgery because of an estimated high surgical risk. Percutaneous mitral valve repair with the MitraClip system resembles the Alfieristitch where a clip is used to connect the tip of the mitral valve leaflets. MATERIAL AND METHODS: Sixteen patients with MR of various origins (functional/degenerative) were treated with the MitraClip system. All patients were highly symptomatic with dyspnoea (New York Heart Association (NYHA) grade three) and MR grade three or more, and had been turned down for surgery due to an excessively high risk. RESULTS: MR was reduced in all but one patient, generally from grade 3.5±0.5 to grade 1.4±0.9. A total of four patients (25%) received two clips. Thirty-day complications were as follows: one patient died, one had a stroke (speech sequelae), one patient had a new chord rupture that was treated surgically. During 90 days of follow-up, symptoms of dyspnoea diminished (reduction of 1 NYHA grade) and the 6-minute walk test results improved from 171±99 to 339±134 metres (p<0.001). CONCLUSION: Percutaneous mitral valve repair with the MitraClip system is now available in Denmark. The treatment is a reasonable alternative in patients with MR and a high estimated surgery risk. FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.

Differences in left ventricular remodelling in patients with aortic stenosis treated with transcatheter aortic valve replacement with corevalve prostheses compared to surgery with porcine or bovine biological prostheses.

Aims: Patients with severe aortic stenosis (AS) can be considered for treatment with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The purpose of this study was to compare left ventricular (LV) remodeling in patients with AS after treatment with TAVR or SAVR. Methods and results: This is an echocardiographic substudy of the NOTION trial, a randomized all-comers trial comparing TAVR with SAVR in patients above 70 years of age. Transthoracic echocardiograms were performed at baseline, 3 and 12 months after TAVR and SAVR. About 232 patients were included in the study, 120 were randomized to TAVR and 112 to SAVR. From baseline to 12 months post-procedure, aortic valve area (AVA) increased in both groups, but with a larger increase in the TAVR group (0.65 ± 0.04 cm2 vs. 1.02 ± 0.05 cm2 for SAVR and TAVR group, P < 0.0001). At 12 months, LV mass regression was more pronounced in the SAVR group as compared with TAVR (17.5% vs. 7.2%, P < 0.001). In the TAVR group at 12 months, end diastolic volume (EDV) increased by 10.2 ± 2.5 ml and, in the SAVR group, EDV decreased by 15.4 ± 2.6 ml with a statistically significant difference between the two groups (P < 0.0001). Paravalvular leakage (PVL) and pacemaker implantations were more common in patients treated with TAVR, which was associated with an increase in EDV (P < 0.01). Conclusion: Patients undergoing SAVR had a larger LV mass regression at 1 year compared with patients undergoing TAVR, which may be due to increasing amounts of PVL and pacemakers in the TAVR group.

No clinical effect of prosthesis-patient mismatch after transcatheter versus surgical aortic valve replacement in intermediate- and low-risk patients with severe aortic valve stenosis at mid-term follow-up: an analysis from the NOTION trial.

OBJECTIVES: Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) for severe aortic valve stenosis (AVS) is common, but less common after transcatheter aortic valve replacement (TAVR) in patients considered at high risk for death after surgery. The objectives of this study were to determine incidence and clinical effect of PPM after SAVR and TAVR in a primarily low-risk patient group. METHODS: Patients 70 years or older with severe isolated AVS, regardless of predicted operative mortality risk, were consecutively randomized 1:1 to TAVR using a self-expandable bioprosthesis (n = 145) or SAVR (n = 135). Post-procedure PPM was graded after 3 months as follows: Not present-mild, if indexed effective orifice area (iEOA) >0.85 cm2/m2, moderate, if 0.65 cm2/m2 < iEOA ≤ 0.85 cm2/m2 and severe, if iEOA ≤0.65 cm2/m2. Outcomes were major adverse cardiac and cerebrovascular events (MACCE, e.g. composite rate of all-cause death, stroke, myocardial infarction or valve reintervention), cardiac-related hospitalizations and New York Heart Association (NYHA) functional class after 2 years. RESULTS: The incidence and the severity of PPM were significantly lower after TAVR compared with SAVR (severe, moderate, none-mild 14.0, 35.5, 50.4 vs 33.9, 36.7, 29.4%; P<0.001). PPM resulted in similar higher mean valve gradients at 3 months for both groups. Baseline characteristics related to severe PPM were younger age, absence of diabetes mellitus, lower mortality-risk score for TAVR, and younger age and higher body mass index for SAVR. At 2 years, there were numerical but no statistically significant differences between both TAVR and SAVR patients with severe and no severe PPM for MACCE (0.0 vs 12.8% for TAVR; P = 0.13, and 13.5 vs 7.0% for SAVR; P = 0.27), number of cardiac-related hospitalizations (mean ± standard deviation 0.4 ± 0.6 vs 0.6 ± 0.8; P = 0.23, and 0.4 ± 0.8 vs 0.5 ± 0.9; P = 0.70) and NYHA functional class (Class I/II/III/IV: 64.7/29.4/5.9/0.0 vs 62.1/34.7/3.2/0.0%, respectively; P = 0.91, and 71.4/25.7/2.9/0.0 vs 72.9/22.9/4.3/0.0%, respectively; P = 0.92). CONCLUSIONS: The incidence of PPM was lower and less severe after TAVR compared with SAVR in intermediate- and low-risk patients with severe AVS. There were no significant differences in MACCE, cardiac-related hospitalizations or NYHA class after 2 years for patients with versus those without severe PPM.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis: 1-Year Results From the All-Comers NOTION Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients. OBJECTIVES: The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. METHODS: Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. RESULTS: A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. CONCLUSIONS: In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial [NOTION]; NCT01057173).

Effect of increasing pump speed during exercise on peak oxygen uptake in heart failure patients supported with a continuous-flow left ventricular assist device. A double-blind randomized study.

AIMS: Continuous-flow left ventricular assist device (CF-LVAD) implantation is associated with improved quality of life, but the effect on exercise capacity is less well documented. It is uncertain whether a fixed CF-LVAD pump speed, which allows for sufficient circulatory support at rest, remains adequate during exercise. The aim of this study was to evaluate the effects of fixed versus incremental pump speed on peak oxygen uptake (peak VO2) during a maximal exercise test. METHODS AND RESULTS: In CF-LVAD (HeartMate II) patients exercise testing measuring peak oxygen uptake (VO2) was performed on an ergometer bike twice in one day: once with fixed pump speed (testfix) and once with incremental pump speed (testinc). The order of testfix and testinc in each patient was determined by randomization. During testinc pump speed was increased from the baseline value by 400 rpm/2 min. Fourteen patients (aged 23­69 years) were included with a mean support duration of 465±483 days. Baseline CF-LVAD speed was 9357±238 rpm and during testinc speed was increased by a mean of 1486±775 rpm. Mean peak VO2 was significantly higher in testinc compared with testfix (15.4±5.9 mL/kg/min vs. 14.1±6.3 mL/kg/min; P=0.012), corresponding to a 9.2% increase. All exercise tests (n=28) were adequately performed with RER>1. CONCLUSION: Increasing pump speed during exercise augments peak VO2 in patients supported with CF-LVADs. An automatic speed-change function in future generations of CF-LVADs might improve functional capacity.

The Nordic aortic valve intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial.

BACKGROUND: Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting. METHODS/DESIGN: This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012. DISCUSSION: The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01057173.

Central and peripheral blood flow during exercise with a continuous-flow left ventricular assist device: constant versus increasing pump speed: a pilot study.

BACKGROUND: End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. METHODS AND RESULTS: Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min(-1); mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min(-1); P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min(-1) per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s(-1) during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s(-1)) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s(-1) at 60 W (P<0.01). CONCLUSIONS: With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

[Eisenmenger syndrome]. / Eisenmengers syndrom.

Congenital heart disease with left-to-right shunt can induce proliferation, vasoconstriction and thrombosis in the pulmonary vascular bed. Eventually, the patient may develop Eisenmenger syndrome defined as pulmonary arterial hypertension caused by high pulmonary vascular resistance with right-to-left shunt and cyanosis. Patients with Eisenmenger syndrome suffer a high risk of complications in connection with acute medical conditions, extra-cardiac surgery and pregnancy. This article describes the precautions that should be taken to reduce morbidity and mortality in these patients.

[Destination therapy in end-stage heart failure. A possible alternative to heart transplantation?]. / Destinationsterapi ved terminalt hjertesvigt. Et muligt alternativ til hjertetransplantation?

The incidence of heart failure continues to increase but the number of available heart donors is limited. Implantation of circulatory assist devices as a permanent alternative to heart transplantation has become a promising new alternative in patients not eligible for heart transplantation (destination therapy). New technical advances have increased the durability of the devices and reduced complications.New generations of rotator pumps are smaller and more durable and will expand the use of these devices for destination therapy. This review discusses the current state of knowledge and indications for destination therapy in end-stage heart failure.

[The Mechanical Heart--HeartMate 1--Danish results]. / Det mekaniske hjerte--HeartMate 1--de danske resultater.

INTRODUCTION: In 1998 the Heart Centre at the Danish National University Hospital implemented a new programme with long-term mechanical circulatory assist to patients with terminal heart failure who could not wait for a donor heart. A so-called Mechanical Heart, HeartMate 1, was to replace a failing left ventricle so that the patient could be resuscitated and await heart transplantation. The aim of the present study is to describe the results of this new treatment in Denmark. MATERIALS AND METHODS: A total of 28 patients with a mean age of 41 years were treated with the HeartMate 1 system in the period 1998 to 2006. Two patients had the system changed to a new HeartMate 1 due to mechanical problems. Both patients were later successfully heart transplanted. A third patient had the system successfully changed to a HeartMate 2 and he is waiting for a donor heart. RESULTS: Hemodynamic observations reveal fast improvement after implantation of the HeartMate system. Patients who were later heart transplanted had the HeartMate system implanted for a mean of 220 days. About 90% of those that were transplanted later improved due to the system from New York Heart Associations class IV to class I-II and they could often be discharged to a normal social life with a well-functioning HeartMate. Calculated 1-year survival with the HeartMate system was 82%. CONCLUSION: Patients with terminal heart failure can be treated and improved by implantation of the HeartMate system and await successful heart transplantation. Permanent advanced assist systems do exist today and these can be applied as a final treatment in selected patients--so-called destination therapy with mechanical circulatory support. The present study shows that it is very likely that the Heart Centre at the Danish National University Hospital will be able to establish a well-functioning programme for destination therapy.