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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

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.

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.

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.

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

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.

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.

Background The arterial switch operation is the current treatment for transposition of the great arteries. Long-term outcome mainly depends on the patency of the transferred coronary arteries. This study assessed the presence of abnormal coronary findings and neoaortic root dilation late after arterial switch operation. Methods In 30 adult patients after arterial switch operation (22 men, 22 ± 3 years), computed tomography angiography was performed to assess the coronary anatomy and abnormal coronary findings, defined as significant stenosis, interarterial coronary course, and acute angled coronary origins. Neoaortic root dimensions and coronary takeoff height were also assessed. Results The most common coronary anatomy pattern was found in 24 of 30 patients. Variant anatomy patterns were seen in 6 patients (5 with aberrant circumflex artery, 1 with a single ostium). The prevalence of abnormal coronary findings was higher in patients with variant coronary pattern as compared with patients with common coronary pattern (100% and 29%, respectively; p = 0.003). In particular, an acute angle of the coronary origin was frequently observed. In patients with an acute angle, larger dimensions of the aortic annulus ( p = 0.016) and the sinus of Valsalva ( p = 0.002) were observed. Moreover, a higher takeoff of the right ( p = 0.030) and left ( p = 0.002) coronary ostium was noted in patients with acute angles. Conclusions Abnormal coronary findings were frequently observed in adult patients after arterial switch operation, especially in patients with a variant coronary anatomy pattern. Neoaortic root dilation and a higher coronary takeoff may explain part of the pathophysiology. Long-term follow-up is needed to determine the clinical significance of these findings.

Intramyocardial injection of human bone marrow-derived MSCs has been demonstrated to improve cardiac function in experimental acute myocardial infarction (AMI) models. However, the effect of intramyocardial MSC treatment in AMI patients is unknown. Therefore, we investigated the short and long term

Intramyocardial bone marrow cell injection is currently being investigated as a new therapeutic option for the treatment of chronic myocardial ischemia. Experimental studies and early phase clinical trials established a favorable safety profile of this approach and suggested that bone marrow cell injection was associated with clinical and functional improvements. Recently, a randomized, double-blind, placebo-controlled trial demonstrated that intramyocardial bone marrow cell injection was associated with beneficial effects on myocardial perfusion and anginal symptoms. However, the mechanisms by which bone marrow cells may improve myocardial perfusion are only partially understood, and several issues remain to be addressed. This review aims to provide a summary of the current experience with bone marrow cell therapy as a novel treatment option for patients with chronic myocardial ischemia. Therefore, the most frequently used cell types will be reviewed along with the mechanisms through which bone marrow cells may improve myocardial perfusion and function. In addition, possible routes of delivery are compared, and the results of currently available experimental and clinical studies are discussed.

Background— The present substudy of a recently published randomized trial aimed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. Methods and Results— In a total of 50 patients, diastolic function was evaluated before and 3 months after bone marrow cell injection using standard echocardiography and strain analysis. In addition, MRI-derived transmitral flow measurements were obtained in a subset of 36 patients. Left ventricular ejection fraction increased from 50±5% to 54±7% in the bone marrow cell group, which was a significant improvement as compared with the placebo group (52±5% versus 51±7%, P =0.001). Filling pressure estimate E/E′ ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group, whereas no improvement was observed in the placebo group (13±4 versus 13±5). The improvement in E/E′ ratio was significantly larger in the bone marrow cell group ( P =0.008). Furthermore, the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group (+0.16±0.25 versus −0.04±0.21, P =0.01), which was mainly related to an increase in the early (E) peak flow rate in the bone marrow cell group (from 407±96 mL/s to 468±110 mL/s, P =0.009 as compared with the placebo group). Conclusions— The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR400/ISRCTN58194927.

Context Previous studies have suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular (LV) function in patients with chronic myocardial ischemia. Objective To investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial at a Netherlands university hospital, May 1, 2005-March 3, 2008 (6-month follow-up ended September 2008) of 50 patients with chronic myocardial ischemia ( mean age [SD], 64 [ 8] years; 43 men). Inclusion criteria: severe angina pectoris despite optimal medical therapy and myocardial ischemia. All patients were ineligible for conventional revascularization. Interventions Intramyocardial injection of 100 x 106 autologous bone marrow derived mononuclear cells or placebo solution. Main Outcome Measures Primarily, the summed stress score, a 17-segment score for stress myocardial perfusion assessed by Tc-99m tetrofosmin single-photon emission computed tomography ( SPECT). Secondary included LV ejection fraction (LVEF), Canadian Cardiovascular Society (CCS) class, and Seattle Angina Questionnaire quality-of-life score ( mean difference >5% considered clinically significant). Results After 3-month follow-up, the summed stress score (mean [SD]) improved from 23.5 (4.7) to 20.1 (4.6) (P

Purpose To evaluate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. Materials and Methods In 24 patients (19 male; 65 ± 9 years) with refractory angina (Canadian Cardiovascular Society [CCS] class III–IV) 84.6 ± 28.7 × 106 bone marrow-derived mononuclear cells were injected intramyocardially (using the NOGA system) in regions with ischemia on Tc-99m tetrofosmin single photon emission computed tomography (SPECT). Diastolic function was evaluated at baseline and at three months using magnetic resonance imaging (MRI) and tissue Doppler imaging (TDI). Results MRI revealed an increased early (E) peak filling rate (374 ± 121 mL/second vs. 412 ± 102 mL/second; P = 0.04), whereas the atrial (A) peak filling rate remained unchanged (340 ± 81 mL/second vs. 334 ± 93 mL/second; P = not significant [NS]). The E/A peak flow ratio increased from 1.09 ± 0.33 to 1.23 ± 0.47 at three months (P = 0.02). TDI demonstrated a significant improvement in early diastolic velocity (E′) from 4.4 ± 1.7 cm/second to 4.8 ± 1.6 cm/second at three months (P = 0.03), whereas the late diastolic velocity (A′) remained unchanged (6.0 ± 1.6 cm/second vs. 6.0 ± 1.7 cm/second; P = NS). Consequently, the E′/A′ ratio increased from 0.74 ± 0.19 to 0.84 ± 0.28 at three months (P = 0.02). Conclusion Intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia improved MRI and TDI-derived parameters of diastolic function. J. Magn. Reson. Imaging 2008;27:992–997. © 2008 Wiley-Liss, Inc.

The present study investigated the safety, feasibility, and potential efficacy of autologous bone marrow cell injection in patients with chronic myocardial infarction and severe left ventricular (LV) dysfunction. In 15 patients (63 +/- 9 years; 14 men) bone marrow was aspirated from the iliac crest. Using the NOGA system (Biosense-Webster, Waterloo, Belgium), 94 +/- 14 x 10(6) bone marrow-derived mononuclear cells were injected into the infarction border zone. Bone marrow cell injection was performed without periprocedural complications in all patients. At 2.5 months, 1 patient died from worsening heart failure. New York Heart Association class improved from 3.5 +/- 0.5 at baseline to 2.7 +/- 0.8 at 3 months (p0.01) and 2.9 +/- 0.8 at 6 months (p0.01 vs baseline). LV ejection fraction (technetium-99m tetrofosmin single-photon emission computed tomography) increased from 23 +/- 8% to 27 +/- 9% at 3 months (p = 0.02) and regional wall thickening improved from 12.8 +/- 5.9% to 15.3 +/- 7.2% at 3 months (p = 0.02). Injected myocardial segments displayed a significant improvement in regional wall thickening (6.6 +/- 6.3% vs 11.7 +/- 7.0% at 3 months, p0.01) and perfusion score (3.5 +/- 0.7 vs 3.0 +/- 0.9 at 3 months, p = 0.02) and a trend toward an improved fluorine-18 fluorodeoxyglucose score (2.9 +/- 0.9 vs 2.6 +/- 1.0 at 3 months, p = 0.06). Regional wall thickening (16.5 +/- 8.9% vs 19.1 +/- 9.1% at 3 months, p = NS), perfusion score (1.8 +/- 0.4 vs 1.7 +/- 0.5 at 3 months, p = NS), and fluorodeoxyglucose score (1.7 +/- 0.4 vs 1.6 +/- 0.4 at 3 months, p = NS) did not improve in noninjected myocardial segments. In conclusion, bone marrow cell injection in patients with chronic myocardial infarction and severe LV dysfunction is safe and feasible and appears to be associated with a decrease in heart failure symptoms and an improved LV function.

Cell therapy has recently been introduced to treat patients with refractory angina. Because most studies have only included short-term follow-up, the effects of cell therapy over a longer period are unknown.In 25 patients (mean age 64 +/- 10 years, 21 men) with refractory angina, a total of 84 +/- 29 x 10(6) bone marrow-derived mononuclear cells was injected intramyocardially in regions with ischemia on technetium-99m tetrofosmin single-photon emission computed tomography. Anginal symptoms and quality of life were evaluated at baseline and at 3, 6, and 12 months. Gated single-photon emission computed tomography was performed at baseline and at 3 and 12 months to assess myocardial perfusion and left ventricular function.Bone marrow cell injection was performed without any complication. At 7 months, one patient died of intracranial hemorrhage. Canadian Cardiovascular Society class improved from 3.4 +/- 0.5 to 2.3 +/- 0.6 at 3 months, 2.4 +/- 0.6 at 6 months, and 2.7 +/- 0.8 at 12 months (P.01). Quality of life improved from 53% +/- 10% to 71% +/- 11% at 3 months, 72% +/- 14% at 6 months, and 68% +/- 14% at 12 months (P.01). The number of segments with ischemia per patient decreased from 4.7 +/- 3.3 to 2.1 +/- 2.6 at 3 months and 1.6 +/- 2.5 at 12 months (P.01). Left ventricular ejection fraction increased from 47% +/- 13% to 53% +/- 17% at 3 months and 51% +/- 17% at 12 months (P.01). Regional wall motion improved from 5.9 +/- 1.7 to 6.6 +/- 2.2 mm at 3 months and 6.4 +/- 2.0 mm at 12 months (P = .01).Autologous bone marrow cell injection in patients with ischemia is safe and results in a sustained beneficial effect on anginal symptoms, myocardial perfusion, and left ventricular function.

Bone marrow cell transplantation has been proposed as a novel therapeutic option for patients with coronary artery disease. This study investigated whether autologous bone marrow-derived mononuclear cell injection into the ischemic myocardium of patients with severe angina pectoris could safely reduce anginal symptoms, improve myocardial perfusion, and increase left ventricular (LV) function. In a total of 20 patients (63 +/- 10 years old; 16 men) with angina pectoris, myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 30 to 100 million mononuclear cells. Anginal symptoms, Canadian Cardiovascular Society class, and quality of life were assessed at 3 and 6 months of follow-up. At baseline and 3 months of follow-up, an exercise test, gated single-photon emission computed tomography, and magnetic resonance imaging were performed to assess exercise capacity, myocardial perfusion, and LV function. Intramyocardial injection of autologous bone marrow-derived mononuclear cells was safe. The Canadian Cardiovascular Society class improved from 3.5 +/- 0.5 at baseline to 2.4 +/- 0.6 after 3 months (p0.01) and 2.4 +/- 0.6 after 6 months (p0.01). The quality-of-life score improved from 52 +/- 10% to 71 +/- 10% at 3 months (p0.01) to 73 +/- 15% at 6 months (p0.01). The exercise capacity increased from 79 +/- 31% to 84 +/- 29% (p0.05). Magnetic resonance imaging revealed an increased LV ejection fraction from 51 +/- 11% to 54 +/- 10% (p0.01) and a reduced LV end-systolic volume from 97 +/- 50 to 88 +/- 42 ml (p0.01). The wall motion score index improved from 0.36 +/- 0.32 to 0.24 +/- 0.28 (p0.01). The number of segments with stress-induced ischemia decreased from 5.1 +/- 3.2 to 2.3 +/- 2.6 (p0.01). In conclusion, autologous bone marrow-derived mononuclear cell injection in patients with ischemia is safe, reduces anginal symptoms, improves myocardial perfusion, and increases LV function.

Cell transplantation is currently being explored as a novel therapeutic option for patients with chronic myocardial ischaemia. The main goal of bone marrow cell transplantation is to augment blood flow in ischaemic myocardium through induction of angiogenesis. Improved collateral perfusion and enhanced left ventricular function have already been documented in animal models with chronic myocardial ischemia.1 Until now, most clinical studies were carried out in patients with acute myocardial infarction. Only two studies containing ⩽10 patients assessed the safety and feasibility of autologous bone marrow cell transplantation in patients with angina and ischaemia.2,3 Further studies are needed to confirm the safety, feasibility and effectiveness reported in these pilot trials. The present phase I/II study tested the feasibility, safety and clinical effects of trans-endocardial transplantation of autologous bone marrow-derived mononuclear cells in patients with drug-refractory angina and myocardial ischaemia. Moreover, we aimed to determine whether cell transplantation is associated with improved myocardial function and perfusion by means of technetium-99m tetrofosmin gated single photon emission computed tomography (SPECT). Patients with ischaemia on technetium-99m tetrofosmin SPECT and with Canadian Cardiovascular Society (CCS) class III or IV angina pectoris (despite maximal tolerated medical treatment) without options for conventional revascularisation were included in the study. An independent expert panel that reviewed the angiograms determined the ineligibility for surgical or percutaneous revascularisation. Seventeen patients fulfilled the inclusion criteria and were considered for inclusion. Exclusion criteria were acute myocardial infarction