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Samenvatting E-health maakt het mogelijk om goede poliklinische zorg aan hartinfarctpatiënten te leveren, zelfs gedurende de huidige COVID-19-pandemie. We deden een haalbaarheidsonderzoek om te kijken of e-health kan worden ingezet als een bruikbaar alternatief voor fysieke polikliniekbezoeken bij het leveren van poliklinische zorg. We verdeelden 200 hartinfarctpatiënten at random over een e-health-interventie of standaard follow-up. De primaire uitkomst was bloeddrukregulatie, secundaire uitkomsten waren patiënttevredenheid en klinische opnamen. Tussen beide groepen waren er geen significante verschillen in uitkomsten. E-health produceert daarmee gelijke uitkomsten.

Introduction The treatment options for advanced heart failure patients drastically changed with the introduction of left ventricular assist devices (LVADs), either as bridge to transplant or as destination therapy for patients ineligible for transplant. Despite major benefits in terms of survival, functional status and quality of life, managing patients with LVADs comes with several challenges. The most significant challenge is balancing between the risks of thrombotic and bleeding complications. Areas covered The present review describes the pathophysiological mechanisms explaining the alterations in the hemostatic profile of LVAD patients, and summarizes current evidence to guide clinical decision making with regard to anticoagulant treatment and management of bleeding complications. Expert opinion LVAD patients require life-long anticoagulant therapy to reduce the risk of pump thrombosis. However, exposing LVAD patients to anticoagulant therapy, in combination with common acquired coagulopathies after LVAD implantation such as acquired von Willebrand syndrome, comes with high risks of bleeding. There is a need for randomized controlled trials in LVAD patients to determine the optimal antithrombotic regimen and find the most effective balance between thrombotic and bleeding complications. In addition, strategies to specifically target the acquired von Willebrand syndrome and its associated angiodysplasias need to be evaluated in the LVAD population.

Purpose Pump thrombosis is a devastating complication after left ventricular assist device implantation. This study aims to elucidate the relation between left ventricular assist device implantation angle and risk of pump thrombosis. Methods Between November 2010 and March 2020, 53 left ventricular assist device-patients underwent a computed tomography scan. Using a 3-dimensional multiplanar reformation the left ventricular axis was reconstructed to measure the implantation angle of the inflow cannula. All patients were retrospectively analyzed for the occurrence of pump thrombosis. Results In 10 (91%) patients with a pump thrombosis, the implantation angle was towards the lateral wall of the left ventricle. In only 20 patients (49%) of the patients without a pump thrombosis the inflow cannula pointed towards the lateral wall of the left ventricle. The mean angle in patients with a pump thrombosis was 10.1 ± 11.9 degrees towards the lateral wall of the left ventricle compared to 4.1 ± 19.9 degrees towards the septum in non- pump thrombosis patients (P

Introduction Cardiac symptoms are one of the most prevalent reasons for emergency department (ED) visits [1], however most of these patients do not have acute cardiovascular disease. This leads to ED overcrowding which subsequently leads to worse patient outcomes and increased costs [2,3]. Attempts to reduce overcrowding have focused mostly on in-hospital triage. The Hollands-midden Acute Regional Triage – cardiology (HART-c) study uses a newly developed triage platform which includes live monitoring, real-time admission capacity, in-hospital data and cardiologist consultation for improved prehospital triage. Purpose The HART-c study aims to safely increase the percentage of patients with cardiac symptoms not referred to the hospital after emergency medical service (EMS) consultation. Methods Patients aged 18 years or older visited by the EMS for cardiac symptoms were included in the region Hollands-Midden from September 2019 till March 2020 (non-COVID period) and compared with the year earlier. Patients were excluded when primary PCI was indicated. EMS consultation consisted of medical history, physical examination, vital parameters and ECG. All data were transferred to a newly developed platform combining pre-hospital data, shown in real-time, and hospital data, such as medical records and admission capacity. The paramedic contacted an on-call triage cardiologist and decided whether admission was necessary and, if so, which regional hospital was most appropriate (figure 1). The study objective was defined as the percentage of patients not referred to the hospital after EMS consultation. Safety of the triage method was defined in the non-referred patients in the intervention as the percentage of MACE (death and acute coronary syndrome) 30 days after non-referral. Results In the intervention group 1755 patients (age 69±15 years, 53% men), and in the control group 1629 patients (age 68±15 years, 53% men) were consulted by the EMS during the HART-c study. In the intervention group 11.4% of patients consulted to the EMS were left at home, compared to 5.5% in the control group (figure 2). Logistic regression was performed to evaluate the effect of the triage intervention. The model was corrected for gender, age and seasonal changes. The chance of being left at home after EMS consultation was 2.29 (95% CI 1.73–3.02, p Conclusion Implementation of an innovative triage method successfully increased the percentage of patients with cardiac symptoms safely left at home. Funding Acknowledgement Type of funding sources: None. Triage without (A) and with (B) platformNon-referral in intervention and control

Highlights • A clinical care track including CR referral results in a high CR participation rate. • CR referral is lower in older and non-STEMI patients. • A larger distance to the CR center is associated with a lower CR participation rate., Purpose Cardiac rehabilitation (CR) after hospitalization for acute coronary syndrome (ACS) has shown to reduce mortality, readmissions, and improve quality of life. CR is recommended by international guidelines but previous studies have shown low participation rates. Systematic CR referral might improve CR participation. Methods The present study evaluates CR referral and CR participation of patients hospitalized for ACS in 2017 and treated according to local protocol, which includes systematic CR referral. Participation rate was divided into a group that finished the CR program and drop outs. In addition, factors associated with CR referral and participation rate were evaluated. Results A total of 469 patients eligible for CR were included in the study, of which 377 (80%) were referred for CR and 353 (75%) participated in CR. Ninety percent of participants completed the CR program. Factors independently associated with CR referral included age (50–60 year vs. > 70 year: odds ratio [OR] 4.7, 95% confidence interval [CI] 1.98–11.2), diagnosis (ST-elevation myocardial infarction vs. unstable angina: OR 17.7, CI 7.59–41.7), previous cardiovascular disease (OR 0.4, CI 0.19–0.73) and left ventricular dysfunction vs. normal function (OR 2.2, CI 1.11–4.52). A larger distance to the CR center was associated with lower CR participation ( 20 km: OR 3.1, CI 1.20–7.72). Conclusions Systematic CR referral in ACS patients results in high CR referral (80%) and participation (75%) rates. CR adherence might be further improved by increasing CR referral, especially in older patients and patients with NSTEMI or unstable angina.

Background Early detection of an upcoming episode of decompensated heart failure (HF) and timely adjustment of medical therapy may prevent a HF hospitalization. The novel multisensory cardiac implantable electronic device (CIED) based algorithm entitled HeartLogic™ (HL) aims to alert in case of upcoming fluid retention. This study investigates the performance of an HL alert in chronic HF patients in an ambulant HF care-path. Methods All chronic HF patients with a CIED and an activated HL algorithm implanted in our centre since 2018 were included. Patients were followed from 01–01–2018 until 01–02–2021 according to the HL-based care-path (Figure 1). The HL index was automatically generated from sensors assessing S3, S3/S1, thoracic impedance, respiratory- and night heartrate. Indexes were monitored continuously and an alert was issued when the pre-set threshold of 16 was surpassed. An alert was classified as true positive when the patient had at least two symptoms and/or signs of congestion during the alert episode. An alert was considered false positive when the patient had not more than one symptom or sign of congestion during the alert episode. If a patient had at least two symptoms and/or signs of congestion without an HL alert, the episode was classified as false negative. Results In total, 100 patients (median age 69 years [IQR 60–77], 78% male) were included. The etiology of HF was ischemic in 45% and 71% had a CRT-D device. Median follow-up was 13 months [IQR 6–23] and in total the follow-up comprised 126 patient-years. In 56 patients, there were 132 alerts, mean alert rate was 1.05 per patient-year. As it was unfeasible to strictly follow the specific HL care-path in 13 alert episodes, these alerts were excluded from further analyses. Based on the remaining 119 alert episodes, the positive predictive value for early detection of congestion was 77% and the negative predictive value was 97%. Sensitivity was 79% and specificity 97%. Conclusion In a real-world HF population, the HL algorithm can accurately predict an upcoming episode of decompensated heart failure. Funding Acknowledgement Type of funding sources: None. Overview of the HL based care-path

BackgroundThoracic irradiation is one of the cornerstones of Hodgkin lymphoma (HL) treatment, which contributes to high rates of long-term survivorship, but begets a life-long increased risk of heart disease including heart failure. At the cardio-oncology (CO) clinic, persistent sinus tachycardia or elevated resting heart rate (RHR) is frequently observed in these patients. The aim of this study was to evaluate the relation between RHR and left ventricular (LV) dysfunction.MethodsIn 75 HL survivors visiting our CO-clinic echocardiographic evaluation of LV systolic and diastolic function including global longitudinal strain (GLS) was performed to assess subclinical LV dysfunction.ResultsMedian age of HL diagnosis was 24 [25th-75th percentile: [19], [29]] years with a 17 [12], [25] year interval to CO-clinic visit and 31 patients (41%) were male. Average RHR was 78 ± 14 bpm and 40% of patients (N = 30) had an elevated RHR defined as ≥ 80 bpm. While there was no difference in LV ejection fraction (55.6 ± 4.3 vs. 54.8 ± 6.6; p = 0.543), patients with elevated RHR had abnormal GLS (-15.9% vs. −18.3%, p = 0.045) and higher prevalence of diastolic dysfunction (73.3% vs. 46.7%; p = 0.022). GLS, E/e’ ratio and presence of diastolic dysfunction were independently associated with RHR when correcting for age, sex and mantle field irradiation. A significant improvement was observed of the RHR-association model with solely extracardiac confounders when LV-function parameters were added to the model (F-statistic = 6.36, p = 0.003).ConclusionsThis study indicates RHR as a possible marker for subclinical LV-dysfunction in HL survivors.

Aims: Major adverse event (MAE) rates during left ventricular assist device (LVAD) therapy in advanced heart failure (HF) patients are high, and impair quality of life and survival. Prediction and risk stratification of MAEs in order to improve patient selection and thereby outcome during LVAD therapy is therefore warranted. Circulating natriuretic peptides (NPs) are strong predictors of MAEs and mortality in chronic HF patients. However, whether NPs can identify patients who are at risk of MAEs and mortality or tend toward myocardial recovery after LVAD implantation is unclear. The aim of this systematic review is to analyze the prognostic value of circulating NP levels before LVAD implantation for all-cause mortality, MAEs and myocardial recovery after LVAD implantation.Methods and Results: Electronic databases were searched for studies analyzing circulating NP in adults with advanced HF before LVAD implantation in relation to mortality, MAEs, or myocardial recovery after LVAD implantation. Twenty-four studies published between 2008 and 2021 were included. Follow-up duration ranged from 48 hours to 5 years. Study sample size ranged from 14 to 15,138 patients. Natriuretic peptide levels were not predictive of all-cause mortality. However, NPs were predictive of right ventricular failure (RVF) and MAEs such as ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization. No relation between NPs and myocardial recovery was found.Conclusion: This systematic review found that NP levels before LVAD implantation are not predictive of all-cause mortality after LVAD implantation. Thus, NP levels may be of limited value in patient selection for LVAD therapy. However, NPs help in risk stratification of MAEs and may be used to identify patients who are at risk for RVF, ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization after LVAD implantation.

AIMS: The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic™ algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period. METHODS AND RESULTS: Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 ± 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025). CONCLUSION: Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits. ispartof: ESC HEART FAILURE vol:8 issue:2 pages:1541-1551 ispartof: location:England status: published

Objective To assess whether the COVID-19 lockdown in 2020 had negative indirect health effects, as people seem to have been reluctant to seek medical care. Methods All emergency medical services (EMS) transports for chest pain or out-of-hospital cardiac arrest (OHCA) in the Dutch region Hollands-Midden (population served > 800,000) were evaluated during the initial 6 weeks of the COVID-19 lockdown and during the same time period in 2019. The primary endpoint was the number of evaluated chest pain patients in both cohorts. In addition, the number of EMS evaluations of ST-elevation myocardial infarction (STEMI) and OHCA were assessed. Results During the COVID-19 lockdown period, the EMS evaluated 927 chest pain patients (49% male, age 62 ± 17 years) compared with 1041 patients (51% male, 63 ± 17 years) in the same period in 2019, which corresponded with a significant relative risk (RR) reduction of 0.88 (95% confidence interval (CI) 0.81–0.96). Similarly, there was a significant reduction in the number of STEMI patients (RR 0.52, 95% CI 0.32–0.85), the incidence of OHCA remained unchanged (RR 1.23, 95% CI 0.83–1.83). Conclusion During the first COVID-19 lockdown, there was a significant reduction in the number of patients with chest pain or STEMI evaluated by the EMS, while the incidence of OHCA remained similar. Although the reason for the decrease in chest pain and STEMI consultations is not entirely clear, more attention should be paid to the importance of contacting the EMS in case of suspected cardiac symptoms in possible future lockdowns.

IntroductionEmergency department (ED) overcrowding is a major healthcare problem associated with worse patient outcomes and increased costs. Attempts to reduce ED overcrowding of patients with cardiac complaints have so far focused on in-hospital triage and rapid risk stratification of patients with chest pain at the ED. The Hollands-Midden Acute Regional Triage—Cardiology (HART-c) study aimed to assess the amount of patients left at home in usual ambulance care as compared with the new prehospital triage method. This method combines paramedic assessment and expert cardiologist consultation using live monitoring, hospital data and real-time admission capacity.Methods and analysisPatients visited by the emergency medical services (EMS) for cardiac complaints are included. EMS consultation consists of medical history, physical examination and vital signs, and ECG measurements. All data are transferred to a newly developed platform for the triage cardiologist. Prehospital data, in-hospital medical records and real-time admission capacity are evaluated. Then a shared decision is made whether admission is necessary and, if so, which hospital is most appropriate. To evaluate safety, all patients left at home and their general practitioners (GPs) are contacted for 30-day adverse events.Ethics and disseminationThe study is approved by the LUMC’s Medical Ethics Committee. Patients are asked for consent for contacting their GPs. The main results of this trial will be disseminated in one paper.DiscussionThe HART-c study evaluates the efficacy and feasibility of a prehospital triage method that combines prehospital patient assessment and direct consultation of a cardiologist who has access to live-monitored data, hospital data and real-time hospital admission capacity. We expect this triage method to substantially reduce unnecessary ED visits.

Heart failure (HF) hospitalisations due to decompensation are associated with shorter lifeexpectancy and lower quality of life. These hospitalisations pose a significant burden on the patients,doctors and healthcare resources. Early detection of an upcoming episode of decompensationmay facilitate timely optimisation of the ambulatory medical treatment and thereby prevent heartfailure-related hospitalisations. The HeartLogicTM algorithm combines data from five sensors ofcardiac implantable electronic devices into a cumulative index value. It has been developed for earlydetection of fluid retention in heart failure patients. This review aims to provide an overview of thecurrent literature and experience with the HeartLogicTM algorithm, illustrate how the index can beimplemented in daily clinical practice and discuss ongoing studies and potential future developmentsof interest.

Introduction: Vasoplegia is a severe complication after cardiac surgery and is associated with impaired clinical outcome. Pre-operative heart failure (HF) is considered an independent predictor of post-operative vasoplegia. We hypothesize that HF patients are more susceptible to vasoplegia due to altered vascular responsiveness. In this study, vasoresponsiveness in patients undergoing cardiac surgery for HF is investigated. Methods: A prospective, observational study was conducted at Leiden University Medical Center. We included patients with HF (N=18) and without HF (N=18) who underwent cardiac surgery on cardiopulmonary bypass. Vasoresponsiveness was assessed at 4 different timepoints: 1) before induction, 2) after induction, 3) after cessation of cardiopulmonary bypass and 4) on the first postoperative day. The vascular response was recorded as change in systemic vascular resistance (SVR) after the administration of phenylephrine (bolus 2 μg/kg). Results: Thirty-six patients were included [67 (61-71) years, 78% male]. Vascular responsiveness was significantly attenuated in patients with HF compared to controls. The response to phenylephrine was already diminished at baseline in HF patients and was almost abolished after cessation of cardiopulmonary bypass (Figure). Roughly the same pattern of vasoresponsiveness was found when excluding patients that received norepinephrine. Moreover, HF patients required a significantly higher amount of noradrenaline [169.80 (IQR 14.77-318.97) ug/kg] compared to controls [3.61 (IQR 0-41.60) ug/kg] to maintain similar SVR during the first 24h postoperatively. Conclusions: The vascular responsiveness is altered in patients with HF and this might explain the higher prevalence of vasoplegia in this patient population.

Aim To analyse non-ST-elevation myocardial infarction (NSTEMI) care in the Netherlands and to identify modifiable factors to improve NSTEMI healthcare. Methods This retrospective cohort study analysed hospital and pharmacy claims data of all NSTEMI patients in the Netherlands in 2015. The effect of percutaneous coronary intervention (PCI) during hospitalisation on 1‑year mortality was investigated in the subcohort alive 4 days after NSTEMI. The effect of medical treatment on 1‑year mortality was assessed in the subcohort alive 30 days after NSTEMI. The effect of age, gender and co-morbidities was evaluated. PCI during hospitalisation was defined as PCI within 72 h after NSTEMI and optimal medical treatment was defined as the combined use of an aspirin species, P2Y12 inhibitor, statin, beta-blocker and angiotensin converting enzyme inhibitor/angiotensin II receptor blocker, started within 30 days after NSTEMI. Results Data from 17,997 NSTEMI patients (age 69.6 (SD = 12.8) years, 64% male) were analysed. Of the patients alive 4 days after NSTEMI, 43% had a PCI during hospitalisation and 1‑year mortality was 10%. In the subcohort alive 30 days after NSTEMI, 47% of patients were receiving optimal medical treatment at 30 days and 1‑year mortality was 7%. PCI during hospitalisation (odds ratio (OR) 0.42; 95% confidence interval (CI) 0.37–0.48) and optimal medical treatment (OR 0.59; 95% CI 0.51–0.67) were associated with a lower 1‑year mortality. Conclusion In Dutch NSTEMI patients, use of PCI during hospitalisation and prescription of optimal medical treatment are modest. As both are independently associated with a lower 1‑year mortality, this study provides direction on how to improve the quality of NSTEMI healthcare in the Netherlands.

Importance Smart technology via smartphone-compatible devices might improve blood pressure (BP) regulation in patients after myocardial infarction. Objectives To investigate whether smart technology in clinical practice can improve BP regulation and to evaluate the feasibility of such an intervention. Design, Setting, and Participants This study was an investigator-initiated, single-center, nonblinded, feasibility, randomized clinical trial conducted at the Department of Cardiology of the Leiden University Medical Center between May 2016 and December 2018. Two hundred patients, who were admitted with either ST-segment elevation myocardial infarction or non–ST-segment acute coronary syndrome, were randomized in a 1:1 fashion between follow-up groups using smart technology and regular care. Statistical analysis was performed from January 2019 to March 2019. Interventions For patients randomized to regular care, 4 physical outpatient clinic visits were scheduled in the year following the initial event. In the intervention group, patients were given 4 smartphone-compatible devices (weight scale, BP monitor, rhythm monitor, and step counter). In addition, 2 in-person outpatient clinic visits were replaced by electronic visits. Main Outcomes and Measures The primary outcome was BP control. Secondary outcomes, as a parameter of feasibility, included patient satisfaction (general questionnaire and smart technology–specific questionnaire), measurement adherence, all-cause mortality, and hospitalizations for nonfatal adverse cardiac events. Results In total, 200 patients (median age, 59.7 years [interquartile range, 52.9-65.6 years]; 156 men [78%]) were included, of whom 100 were randomized to the intervention group and 100 to the control group. After 1 year, 79% of patients in the intervention group had controlled BP vs 76% of patients in the control group (P = .64). General satisfaction with care was the same between groups (mean [SD] scores, 82.6 [14.1] vs 82.0 [15.1];P = .88). The all-cause mortality rate was 2% in both groups (P > .99). A total of 20 hospitalizations for nonfatal adverse cardiac events occurred (8 in the intervention group and 12 in the control group). Of all patients, 32% sent in measurements each week, with 63% sending data for more than 80% of the weeks they participated in the trial. In the intervention group only, 90.3% of patients were satisfied with the smart technology intervention. Conclusions and Relevance These findings suggest that smart technology yields similar percentages of patients with regulated BP compared with the standard of care. Such an intervention is feasible in clinical practice and is accepted by patients. More research is mandatory to improve patient selection of such an intervention. Trial Registration ClinicalTrials.gov Identifier:NCT02976376

Background Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. Aims To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. Methods The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. Conclusion The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.

Ventricular assist device (VAD) implantation is an established treatment modality for patients with end-stage heart failure, and improves symptoms and survival. In the Netherlands, it is not yet routinely considered in patients with congenital heart disease and failing systemic right ventricle (SRV). Recently, a VAD was implanted in 2 SRV patients, one who underwent a Mustard procedure during infancy for transposition of the great arteries (male, 47 years old) and one with a congenitally corrected transposition of the great arteries (male, 54 years old). The first patient is doing well >1 year after implantation; the second patient will be discharged home soon. These examples and other reports demonstrate the feasibility of adopting VAD implantation into routine care for SRV failure. In conclusion, patients with SRV failure may be suitable candidates for VAD implantation: they are relatively young, usually have a preserved subpulmonary left ventricular function, and their specific anatomical and physiological characteristics often make them unsuitable for cardiac transplantation. Therefore it is important to recognise the possibility of VAD implantation early in the process of SRV failure, and to timely refer these patients to a heart failure clinic with experience in VAD implantation in this group of patients for optimisation, screening, and implantation. ispartof: NETHERLANDS HEART JOURNAL vol:27 issue:12 pages:590-593 ispartof: location:Netherlands status: published

Background Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved. Methods This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12). Discussion Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome. Trial registration The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

Background: Heart failure with reduced ejection fraction due to a post-infarction anteroseptal aneurysm carries a poor prognosis. Patients with refractory heart failure may be considered for advanced surgery, including left ventricular assist device implantation, heart transplantation and left ventricular reconstruction. The aim of this study was to evaluate outcomes after an integrated approach of left ventricular reconstruction with concomitant procedures (mitral/tricuspid valve repair, coronary revascularization), and assess risk factors for event-free survival, focusing on left ventricular geometry/function and presence of functional mitral regurgitation (MR). Methods: A total of 159 consecutive heart failure patients who underwent left ventricular reconstruction between 2002 and 2011 were included. Mid-term echocardiographic and long-term clinical outcomes were evaluated. Preoperative risk factors were correlated to event-free survival (freedom from mortality, left ventricular assist device implantation, and heart transplantation). Results: Mid-term echocardiography demonstrated decreased indexed left ventricular end-systolic volumes (89 ± 42 mL/m2 preoperatively; 51 ± 18 at mid-term, p < 0.001), and absence of MR ≥ grade 2. Event-free survival was 83% ± 3% at 1-year, 68% ± 4% at 5-year, and 46% ± 4% at 10-year follow-up. Preoperative wall motion score index (WMSI; hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.7–5.8, p < 0.001) and presence of MR ≥ grade 2 (HR 1.9, 95% CI 1.1–3.1, p = 0.014) were independently associated with adverse event-free survival. Conclusions: Event-free survival is favorable in patients with WMSI < 2.5 and significantly worse when WMSI is ≥ 2.5. In both groups, the presence of preoperative MR ≥ grade 2 negatively affects event-free survival, despite successful correction of MR. Risk stratification by preoperative WMSI and MR grade supports the Heart team in choosing the optimal surgical strategy for patients with refractory heart failure.

Background Severely increased right ventricular (RV) afterload is considered a contra-indication for orthotopic liver transplantation (OLT). This study assesses the effects of mildly increased RV afterload on long-term outcome after OLT in relation to RV function. Methods 139 OLT recipients (53 ± 12 years, 76% male) were included. Preoperative RV afterload was assessed invasively or, if not available, echocardiographically and categorised as normal, high-normal (mean pulmonary artery pressure [PAP] 20–25 mmHg or echocardiographic systolic PAP 35–40 mmHg) or mildly elevated (mean PAP 25–35 mmHg or systolic PAP 40–50 mmHg). The association between level of RV afterload, echocardiographic RV function and postoperative outcome was assessed. Results Right ventricular afterload was high-normal in 17% and mildly elevated in 12% of patients. Patients with elevated RV afterload had higher echocardiographic RV dimensions and left ventricular filling pressures. RV functional parameters were within normal range and not associated with RV afterload. Increased RV afterload was associated with a higher incidence of postoperative haemodynamic complications (8%, 17%, and 29% for normal, high-normal and mildly elevated RV afterload, respectively, p = 0.03) and worse survival (8-year survival 74%, 41% and 37% respectively, p = 0.01). Preoperative RV function was not associated with outcome after OLT. Conclusions Increased RV afterload was associated with increased haemodynamic complications and worse long-term survival in OLT recipients. Right ventricular function in patients with increased RV afterload was within normal range and not associated with postoperative outcome.

Background: Polysomnography is the gold standard for detection of central sleep apnea in patients with stable heart failure. However, this procedure is costly, time consuming, and a burden to the patient and therefore unsuitable as a screening method. An electronic health (eHealth) app to measure overnight oximetry may be an acceptable screening alternative, as it can be automatically analyzed and is less burdensome to patients. Objective: This study aimed to assess whether overnight pulse oximetry using a smartphone-compatible oximeter can be used to detect central sleep apnea in a population with stable heart failure. Methods: A total of 26 patients with stable heart failure underwent one night of both a polygraph examination and overnight saturation using a smartphone-compatible oximeter. The primary endpoint was agreement between the oxygen desaturation index (ODI) above or below 15 on the smartphone-compatible oximeter and the diagnosis of the polygraph. Results: The median age of patients was 66.4 (interquartile range, 62-71) years and 92% were men. The median body mass index was 27.1 (interquartile range, 24.4-30.8) kg/m2. Two patients were excluded due to incomplete data, and two other patients were excluded because they could not use a smartphone. Seven patients had central sleep apnea, and 6 patients had obstructive sleep apnea. Of the 7 (of 22, 32%) patients with central sleep apnea that were included in the analysis, 3 (13%) had an ODI≥15. Of all patients without central sleep apnea, 8 (36%) had an ODI

Background It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. Methods and results This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3‑month and P = 0.15 at 12-month follow-up). Conclusion Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. Clinical Trial Registration: NTR2516 Electronic supplementary material The online version of this article (10.1007/s12471-018-1213-2) contains supplementary material, which is available to authorized users.

Introduction Cardiac implanted electronic devices (CIEDs) have significantly improved the survival and quality of life in heart failure patients. The role of implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) in patients with a left ventricular assist device (LVAD) has not been well defined. CIED procedures come at a price of venous access problems, lead malfunctions and pocket complications. This requires creative approaches to tackle CIED related issues in LVAD patients. Case Report Here we describe the clinical course of a 67 year old patient with an LVAD as destination therapy. The heart failure etiology was a non-ischemic cardiomyopathy due to sarcoidosis and he was pacing dependent due to a total atrioventricular block. The patient had an ICD due to recurrent monomorphic ventricular tachycardias and a CRT indication due to previous deterioration of (right sided) heart failure in the temporary absence of biventricular pacing. He recently had a pump thrombosis which was treated medically as he was deemed too frail to undergo a pump exchange. The anticoagulation regimen consisted of a vitamin K antagonist (INR 2.5-3.0) and clopidogrel 75mg o.d.. The patient was admitted for a pulse generator exchange due to low battery voltage. We were confronted with impeding right ventricular lead failure and bilateral venous access problems due to chronic subclavian vein occlusions in a patient with 5 transvenous leads, therapeutic anticoagulation and pronounced thoracic collaterals (Fig 1). Several strategies were considered - venous angioplasty, contralateral lead tunneling and epicardial lead implantation. We sought for a creative solution to deliver biventricular fusion pacing with the existing leads from two contralateral pulse generators. This provided the least invasive solution to deliver effective CRT. Summary This case illustrates the complexity of CIED related decision making in pacing dependent LVAD patients, particularly those with an ICD and CRT indication.

Purpose Patients with continuous-flow (CF) left ventricular assist devices (LVADs) as destination therapy (DT) require anticoagulation with vitamin K antagonists (VKAs). A time in therapeutic range (TTR) of international normalized ratio above 60% is associated with fewer clinical events in atrial fibrillation patients. However, data on this association in LVAD patients are lacking. We therefore aimed to study the association between TTR and clinical events in patients with CF-LVAD as DT. Methods We performed a single center cohort study of patients implanted with a HeartWare LVAD as DT who were discharged from the hospital between 2010 and 2020. Patients were followed from day of discharge until their first event, death or end of follow-up. During follow-up, the TTR ( Results A total of 63 patients were included with a median age of 63 years (range 29-72), under whom 50 (79%) males and 36 (57%) had ischemic heart failure. During 156 years of follow-up, 13 thromboembolic, 19 hemorrhagic, 19 neurologic events and 34 deaths occurred. IRs were slightly higher among patients with a TTR Conclusion A high TTR in patients with a CF-LVAD as DT is associated with fewer thromboembolic and hemorrhagic events and death.

Background: Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR). Methods: Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 μg · kg–1 · min–1 or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min–1 · m–2 or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up. Results: SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009). Conclusions: Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up.

OBJECTIVES: Surgical left ventricular (LV) restoration (SVR) induces changes in LV systolic and diastolic function that may affect postoperative right ventricular (RV) function. This study aimed to evaluate the long-term effect of SVR on RV function, with specific focus on determinants and prognostic implications of RV dysfunction. METHODS: Eighty-six patients (age 60 ± 10 years, 73% male) with clinical and echocardiographic follow-up 2 years after SVR were included. RV dysfunction was defined as RV fractional area change < 35%. The association between RV dysfunction at follow-up and clinical and echocardiographic characteristics and outcome was investigated. RESULTS: RV dysfunction at follow-up was present in 40% of patients and was associated with worse preoperative RV fractional area change (39 ± 9 vs 46 ± 7%, P < 0.01), pulmonary hypertension (18 vs 4%, P= 0.03) and higher follow-up LV filling pressures (E/E' ratio 23± 8 vs 15± 8, P=0.02). At follow-up, patients with RV dysfunction were more frequently in New York Heart Association Class III or IV (30 vs 12%, P= 0.04) and 5-yearmortality, heart transplantation and LV assist device implantation rate was increased (49 vs 17%, P < 0.01) as compared to patients with normal RV function. CONCLUSIONS: RV dysfunction after SVR was observed in 40% of patients and was associated with preoperative RV dysfunction, presence of pulmonary hypertension and an increase in LV filling pressures at follow-up. Patients with RV dysfunction after SVR had worse clinical functioning and outcome as compared to patients with normal RV function.

Optimal left ventricular assist device (LVAD) functioning and preservation of right ventricular (RV) function are major survival determinants in destination therapy (DT)-LVAD recipients. Currently, the indication for routine pump speed optimization in stable patients and its effect on RV function at follow-up remain underexplored. Hemodynamically stable patients (N = 17, age 61 [interquartile range {IQR} 51-66] years; 13 [77%] male) underwent a routine speed ramp test. Echocardiographic images were obtained at incremental speed settings to determine optimal pump speed. In 8 patients (47%), LVAD speed could be optimized. In these patients, RV fractional area change (26% [IQR 23-31] to 35% [IQR 27-45], p = 0.04) and RV longitudinal peak systolic strain (-13% [IQR -16 to -9] to -17% [IQR -18 to -11], p = 0.02) at 3 months follow-up improved without RV dilatation. Furthermore, N-terminal pro-brain natriuretic peptide level decreased (3,162 [IQR 1,336-4,487] ng/L to 2,294 [IQR 1,157-3,810] ng/L, p = 0.02). No significant follow-up changes were found in patients without indication for speed adjustment. In conclusion, routine evaluation of optimal LVAD speed reveals the potential of speed optimization in a substantial proportion of stable LVAD-DT patients and can improve RV function.

Objective Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. Methods A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Results Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was −24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P

Background Intramyocardial injection of bone marrow cells (BMC) in refractory angina patients with chronic myocardial ischemia has shown to be safe and improve clinical status during short-term follow-up. However, scarce data are available on long-term (>12 months) safety and efficacy. Therefore, the occurrence of clinical events and the long-term clinical effects of intramyocardial BMC injection were evaluated in patients with chronic myocardial ischemia up to 10 years after treatment. Methods and Results Patients (n = 100, age 64 ± 9 years, male 88%) with chronic myocardial ischemia who underwent intramyocardial BMC injection between 2004 and 2010 were evaluated. During yearly outpatient clinic visits, the occurrence of clinical events was documented. In addition, clinical status was assessed according to the Canadian Cardiovascular Society (CCS) score and quality of life was measured using the Seattle Angina Questionnaire. These parameters were evaluated at baseline and during the first year, followed by cross-sectional long-term follow-up which was performed in 2011 and 2014. No adverse events considered related to the procedure occurred during 10 years of follow-up. Observed annual mortality rate and annual myocardial infarction rate were 3.8% and 1.9% per year, respectively. When compared to baseline, CCS class and quality of life remained significantly better during 5-year follow-up after BMC treatment (both P

Objectives Vasoplegia has been described as a complication after cardiac surgery, particularly in patients with a poor left ventricular ejection fraction. The aim of this study was to assess the incidence, survival and predictors of vasoplegia in patients undergoing heart failure surgery and to propose a risk model. Methods A retrospective study including heart failure patients who underwent surgical left ventricular restoration, CorCap implantation or left ventricular assist device implantation between 2006 and 2015. Patients were classified by the presence or absence of vasoplegia. Results Two hundred and twenty-five patients were included. The incidence of vasoplegia was 29%. The 90-day survival rate in vasoplegic patients was lower compared with non-vasoplegic patients (71% vs 91%, P < 0.001). After adjusting for age, sex and surgical procedure, anaemia (OR 2.195; 95% CI 1.146, 4.204; P = 0.018) and a higher thyroxine level (OR 1.140; 95% CI 1.033, 1.259; P = 0.009) increased the risk of vasoplegia; a higher creatinine clearance (OR 0.980; 95% CI 0.965, 0.994; P = 0.006) and beta-blocker use (OR 0.257; 95% CI 0.112, 0.589; P = 0.001) decreased the risk. The risk model consisted of the same variables and could adequately identify patients at risk for vasoplegia. Conclusions Vasoplegia after heart failure surgery is common and results in a lower survival rate. Anaemia and a higher thyroxine level are associated with an increased risk on vasoplegia. In contrast, a higher creatinine clearance and beta-blocker use decrease the risk on vasoplegia. These factors are used in the risk model that may guide treatment strategy.

Intramyocardial bone marrow cell injection has been associated with improvements in myocardial perfusion and left ventricular function. The current substudy of a randomized, placebo-controlled, double-blinded study, investigated the effect of intramyocardial bone marrow cell injection on myocardial sympathetic innervation in patients with chronic myocardial ischemia. In a total of 16 patients (64 ± 8 years, 13 men), early and late iodine-123 metaiodobenzylguanidine (MIBG) imaging was performed before and 3 months after intramyocardial bone marrow cell injection. No improvements were observed in global early H/M ratio (P = 0.40), late H/M ratio (P = 0.43) and cardiac washout rate (P = 0.98). However, late 123-I MIBG SPECT defect score showed a trend to improvement in the bone marrow cell group (from 31.0 ± 7.1 to 28.1 ± 14.9) as compared to the placebo group (from 33.6 ± 8.5 to 34.5 ± 9.8, P = 0.055 between groups). This trend was mainly driven by a substantial improvement in three bone marrow cell-treated patients, which all had diabetes and severe MIBG defects. In these patients, the extent and severity of MIBG defects improved substantially independent of myocardial perfusion and cell injection sites. The present study does not demonstrate improvements in global cardiac sympathetic nerve innervation after intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. However, regional analysis of sympathetic nerve innervation reveals improvements in three diabetic patients independent of myocardial perfusion, suggestive of a therapeutic effect on diabetic cardiac sympathetic dysinnervation.

Left ventricular assist device (LVAD) implantation can be challenging in patients with a prior surgical ventricular restoration (SVR). In this case series of heart failure patients with a history of SVR, we describe the surgical technique and outcome of a customized approach for inflow cannula orientation. Seven patients with a history of SVR with end-stage chronic heart failure were accepted for long-Term LVAD support. In all patients, the Dacron patch was removed through left ventriculotomy and a Hegar 22 dilator was inserted at the estimated optimal position of the LVAD inflow cannula. The left ventricle was reconstructed around the dilator from the left ventricular (LV) apex to the base. Finally, the LVAD sewing ring was sutured onto the remaining apical defect and a HeartWare® LVAD was implanted. LVAD implantation was successful in all 7 patients. Transoesophageal echocardiography ensured an adequate LVAD position and inflow and outflow cannula Doppler flow recordings. The mean intensive care unit stay was 5.8 ± 2.6 days, and the hospital stay after surgery was 32 ± 16 days. All patients follow regular visits (follow-up 20 ± 16 months) at the outpatient clinic without any remarkable event. Using the technique described, LVAD implantation in patients after SVR is feasible and safe.

Vasoplegia is a common complication of cardiac surgery, especially in patients with a reduced left ventricular ejection fraction (LVEF). However, uncertainty remains about the risk factors of vasoplegia in patients undergoing heart failure surgery. Patients who underwent heart failure surgery in

☆ Funding: This work was supported by the Transla [TeRM-Smart Mix SSM06004], the BioMedical Materials Heart Foundation [cell therapy program: Translational Department of Cardiology receives unrestricted research Medtronic and Biotronik. ☆☆ Disclosures: None. ⁎ Corresponding author at: Department of Cardiolo Center, Post Office Box 9600, 2300 RC Leiden, The Nether Leiden, The Netherlands. E-mail address: d.e.atsma@lumc.nl (D.E. Atsma). 1 This author takes responsibility for all aspects of the re of the data presented and their discussed interpretation.

Over the past decades, substantial advances in risk factor modification, pharmacological treatment, and revascularisation therapy have significantly reduced the mortality of ischaemic heart disease (IHD). Nevertheless, IHD remains a leading cause of morbidity and mortality. Cell therapy is currently being investigated as a potential treatment modality for patients with IHD. Preclinical studies suggested that cell therapy may have a favourable effect on tissue perfusion and contractile performance by promoting vascularisation and myocyte formation. Following these encouraging preclinical results, cell therapy has rapidly been introduced into the clinical setting. This paper aims to provide an overview of the basic principles of cardiac cell therapy. First, the potential mechanisms through which cell therapy may improve cardiac performance and the different cell populations that have been tested in preclinical studies are discussed. Thereafter, the different routes of cell delivery are reviewed, along with the results of the currently available clinical studies investigating the safety, feasibility and efficacy of cardiac cell therapy for patients with IHD. Originally, cell therapy was thought to improve cardiac performance through transdifferentiation of the injected cells into cardiomyocytes. Although several early studies supported the ability of cell therapy to regenerate cardiomyocytes,1 w1 subsequent studies failed to support these initial observations.w2–4 Since then, it has become apparent that the mechanistic underpinnings of cardiac cell therapy appear to be far more complex (fig 1). Several groups offered fusion of donor cells with host cardiomyocytes as an explanation for previous claims of transdifferentiation.w4 w5 Others reported that cell therapy may promote vascularisation by physical incorporation of the injected cells into new capillaries or in perivascular cells.2 w6 Still, the discrepancy between the massive cell death occurring within 24 h after cell transfer and the sustained functional improvement shown by many groups suggest that other mechanisms may be involved. …

Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate.To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia.Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months.SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/-30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS).Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium.

Cell therapy has been proposed as a novel treatment strategy for patients with ischemic heart disease. However, two recent studies suggested that cardiac cell transplantation might aggravate coronary atherosclerosis. The aim of the current study was to assess whether intramyocardial bone marrow cell transplantation in patients with chronic myocardial ischemia is associated with progression of coronary atherosclerosis.In 30 patients with chronic ischemia, bone marrow was aspirated from the iliac crest. During mononuclear cell isolation, coronary angiography was performed. Thereafter, 94+/-18 x 10(6) cells were injected intramyocardially (NOGA system) in regions with ischemia on technetium-99m tetrofosmin SPECT.During the 12-month follow-up period, there was no clinical evidence of progression of atherosclerosis. CCS class improved from 3.4+/-0.5 to 2.4+/-0.8 at 3 months, 2.4+/-0.9 at 6 months and 2.5+/-0.9 at 12 months (P0.01). MRI-determined left ventricular ejection fraction increased from 51+/-12% to 54+/-12% at 3 months (P0.01) and the number of ischemic segments per patient on SPECT decreased from 5.2+/-2.6 to 2.1+/-2.2 at 3 months (P0.01). Repeat coronary angiography at 4 months revealed that bone marrow cell transplantation did not decrease minimal luminal diameter (1.81+/-0.80 mm versus 1.79+/-0.82 mm, P = NS) or mean luminal diameter (2.48+/-0.85 mm versus 2.46+/-0.86 mm, P = NS). Similarly, the percentage diameter stenosis (32+/-19% versus 32+/-20%, P = NS) and the atheromatosis severity score (4.78+/-2.40 versus 4.80+/-2.40, P = NS) remained unchanged.Intramyocardial bone marrow cell transplantation in patients with chronic myocardial ischemia was not associated with significant progression of atherosclerosis.

Heart failure represents a serious challenge to the healthcare system because of its high prevalence, morbidity and mortality. The pending increase in prevalence due to the ageing population and the relatively poor prognosis of heart failure highlight the necessity to further optimise the organisation of heart failure care [1, 2]. Strategies to enhance the coordination between primary, secondary and tertiary healthcare workers may improve clinical outcome and reduce heart failure associated costs. In the Dutch Alphen-Leiderdorp-Leiden region, collaboration between general practitioners and cardiologists was recently initiated aiming to develop a regional all-phase integrated heart failure care program. A survey among general practitioners in Alphen and heart failure patients of the Alrijne Hospital revealed that patients preferred to receive care from the heart failure clinic, but they wanted their general practitioner to be more involved. General practitioners would appreciate to expand their involvement in heart failure care. Subsequently, a working group was created consisting of cardiologists, heart failure nurses and primary healthcare workers that developed four protocols aiming to streamline patient flow from primary to speciality care and vice-versa. All protocols are in line with the most recent European Society of Cardiology heart failure guideline [3]. The first protocol stipulates the diagnostic measures to be taken by the general practitioner and cardiologist when heart failure is suspected. If the diagnosis is established, the cardiologist identifies the underlying cardiac problem, which is crucial for therapeutic reasons, as the precise pathology determines the specific treatment. The available diagnostic and therapeutic modalities are outlined in the second protocol, which was developed in collaboration with the Leiden University Medical Centre (LUMC). The third protocol describes the seamless transition to long-term management of stable patients. The general practitioner is the main caregiver in stable patients. However, several circumstances necessitate persistent (co)-treatment by a cardiologist in a secondary hospital or in a tertiary referral hospital. The fourth protocol describes the organisation of care for end-stage heart failure patients. The general practitioner mainly delivers palliative care and hospital admissions are prevented. Specific attention is paid to temporary deactivation of implantable cardioverter-defibrillator therapy. The protocols are merged in one flowchart (Fig. 1) to emphasise the all-phase integrated clinical framework for diagnostic and therapeutic decision making in heart failure patients. Fig. 1 Flowchart for all phase integrated diagnostic and therapeutic decision making in heart failure. ACE angiotensin-converting enzyme, (NT-pro) BNP (N-terminal pro) brain natriuretic peptide, BP blood pressure, CMR cardiac magnetic resonance, CRT cardiac ... Co-operation between primary, secondary and tertiary healthcare providers may optimise heart failure care. By working together, tailored care in adherence with the guidelines can be provided as close to home as possible. The current framework complies with the recent recommendations of the World Heart Failure Alliance since it provides a system that delivers timely access to diagnostic services and treatment of heart failure, as well as a seamless transition to long-term care [2]. The concept that a standardised regional program can improve care has already been established in acute infarction patients [4] and resulted in the Dutch national project ‘Connect acute infarction’. Potentially, the presented framework may be used as a start-up for a new national project ‘Connect heart failure’, which may offer a prospective solution to the increasing demand for heart failure care.

Background— Intramyocardial bone marrow cell injection is associated with improvements in myocardial perfusion and anginal symptoms in patients with refractory angina pectoris. This study evaluates the effect of repeated intramyocardial bone marrow cell injection in patients with residual or recurrent myocardial ischemia. Methods and Results— Twenty-three patients (17 men; 69±9 years) who had improved myocardial perfusion after the first injection but had residual or recurrent angina and ischemia on single-photon emission computed tomographic myocardial perfusion imaging were included. Patients again received intramyocardial injection of 100×10 6 autologous bone marrow mononuclear cells, 4.6±2.5 years after their first injection. No periprocedural complications occurred. Myocardial perfusion assessed using single-photon emission computed tomographic myocardial perfusion imaging improved from a summed stress score of 27.3±5.8 at baseline to 24.5±4.4 at 3 months ( P =0.002) and 25.4±4.9 at 12 months of follow-up ( P =0.002). Perfusion improvement after 3 months was comparable with the effect of the first injection ( P =0.379). Anginal complaints improved ≤12 months after cell injection in Canadian Cardiovascular Society score (mean change at 3, 6, and 12 months: 0.6±0.9%, 0.5±0.9%, and 0.6±0.9%, respectively; P slope =0.007, first versus repeated; P =0.188) and in quality of life score as measured by Seattle Angina Questionnaire (mean change at 3, 6, and 12 months: 7±14%, 8±14%, and 7±15%, respectively; P slope =0.020, first versus repeated; P =0.126). Conclusions— Repeated bone marrow cell injection in previously responding patients with refractory angina is associated with improvements in myocardial perfusion, anginal complaints, and quality of life score ≤12 months of follow-up. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR2664.

Purpose Mechanical circulatory support with a continuous-flow left ventricular assist device (LVAD) may be a valuable treatment in end-stage heart failure patients for an extended period of time. The purpose of this study was to evaluate the safety and efficacy of implantation of a continuous-flow LVAD in end-stage heart failure patients within the first destination program in the Netherlands. Methods A third-generation LVAD was implanted in 16 heart failure patients (age 61 ± 8; 81 % male; left ventricular ejection fraction 20 ± 6 %) as destination therapy. All patients were ineligible for heart transplant. At baseline, 3 and 6 months, New York Heart Association (NYHA) functional class, quality-of-life and exercise capacity were assessed. Clinical adverse events were registered. Results Survival at 30 days and 6 months was 88 and 75 %, respectively. In the postoperative phase, 6 (38 %) patients required continuous veno-venous haemofiltration for renal failure and 2 (13 %) patients required extracorporeal membrane oxygenation because of severe right ventricular failure. During follow-up, NYHA functional class and quality-of-life improved from 3.7 ± 0.1 to 2.3 ± 0.1 and 57 ± 5 to 23 ± 3 at 6 months (P

Adjunctive use of abciximab during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) improves clinical outcome. This study addresses the outcome of patients with AMI treated with abciximab, initiated either before transport to a PCI center (early group) or immediately upon arrival at the catheterization laboratory (late group) for primary PCI. Of 446 consecutive patients with AMI, angiographic data and clinical complications were evaluated up to 6 months after primary PCI. Patients received abciximab before transport (early group; n = 138) or just before the intervention (late group; n = 308). Baseline data, including transport time (45 ± 15 min; range, 15–60 min), were comparable in both groups. Early reperfusion was more prevalent in the early group (35% vs. late 19%; P < 0.001). Furthermore, a better final TIMI 3 flow was noted in the early group (91% vs. late 83%; P = 0.05). Although mortality reduction attributable to early abciximab treatment could not be demonstrated, major adverse cardiac events (MACE) occurred in 27% in the early group and 36% in the late group (P = 0.05). Revascularization rates were similar, but repeat acute coronary syndromes were less frequent in the early group (11% vs. late group 20%; P = 0.04). In multivariate analysis, cardiogenic shock, out-of-hospital cardiac arrest, and previously known coronary artery disease were independent predictors of higher MACE rate, whereas early reperfusion and final TIMI 3 flow reduced 6-month MACE rate. Abciximab pretreatment of patients with AMI for primary PCI results in better initial and final TIMI flow and tends to improve 6-month clinical outcome. © 2005 Wiley-Liss, Inc.

We previously showed that intramyocardial bone marrow cell (BMC) injection in patients with refractory angina and chronic myocardial ischemia improves myocardial perfusion, cardiac function and disease-related complaints. Treatment effect varied between patients, but the predictors of response remain to be identified. Therefore, the aim of the present study was to assess whether patient characteristics, procedural data and baseline measurements influence the response to intramyocardial BMC treatment in a large cohort of refractory angina patients.In 120 patients (64 ± 9 years, 88% men) with refractory angina, 97 ± 13 × 10(6) BMCs were injected intramyocardially in regions with stress-inducible ischemia as assessed by single photon emission computed tomography (SPECT). Canadian Cardiovascular Society angina (CCS) class, quality-of-life score, exercise testing, SPECT and magnetic resonance imaging were performed at baseline and at 3 months follow-up demonstrating significant improvements in CCS class, quality-of-life, exercise capacity, myocardial perfusion and left ventricular function (all variables P0.001). Multivariate analysis was performed to evaluate the influence of patient characteristics, procedural data and baseline measurements on BMC treatment response. Based on the improvement of myocardial perfusion at stress, diabetes and a large number of ischemic segments at baseline were shown to be independently associated with a large response to BMC therapy.The present study demonstrates that diabetes and a large number of ischemic segments are predictors of a large response to intramyocardial BMC injection in refractory angina and chronic ischemia. Furthermore, the safety and efficacy results of previous trials are now confirmed in a larger study population.

In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P = 0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.