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Background and Aims In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. Methods The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. Results The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P -values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (P interaction =.03; adjusted P interaction =.33) and diabetics (P interaction =.01; adjusted P interaction =.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. Conclusions This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients. [ABSTRACT FROM AUTHOR]

Heart failure (HF) admissions are burdensome, and the mainstay of prevention is the timely detection of impending fluid retention, creating a window for medical treatment intensification. This study evaluated the accuracy and performance of a Triage-HF-guided carepath in real-world ambulatory HF patients in daily clinical practice. In this prospective, observational study, 92 adult HF patients (71 males (78%), with a median age of 69 [IQR 59–75] years) with the Triage-HF algorithm activated in their cardiac implantable electronic devices (CIEDs), were monitored. Following high-risk alerts, an HF nurse contacted patients to identify signs and symptoms of fluid retention. The sensitivity and specificity were 83% and 97%, respectively. The positive predictive value was 89%, and negative predictive value was 94%. The unexplained alert rate was 0.05 alerts/patient year, and the false negative rate was 0.11 alerts/patient year. Ambulatory diuretics were initiated or escalated in 77% of high-risk alert episodes. In 23% (n = 6), admission was ultimately required. The median alert handling time was 2 days. Fifty-eight percent (n = 18) of high-risk alerts were classified as true positives in the first week, followed by 29% in the second–third weeks (n = 9), and 13% (n = 4) in the fourth–sixth weeks. Common sensory triggers included an elevated night ventricular rate (84%), OptiVol (71%), and reduced patient activity (71%). The CIED-based Triage-HF algorithm-driven carepath enables the timely detection of impending fluid retention in a contemporary ambulatory setting, providing an opportunity for clinical action. [ABSTRACT FROM AUTHOR]

Background: To date, claims data have not been used to study outcome differences between low and high socioeconomic status (SES) patients surviving ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in the Netherlands. Aim: To evaluate STEMI and NSTEMI care among patients with low and high SES in the referral area of three Dutch percutaneous coronary intervention (PCI) centres, using claims data as a source. Methods: STEMI and NSTEMI patients treated in 2015–2017 were included. Patients' SES scores were collected based on their postal code via an open access government database. In patients with low (SES1) and high (SES4) status, revascularisation strategies and secondary prevention medication were compared. Results: A total of 2065 SES1 patients (age 68 ± 13 years, 58% NSTEMI) and 1639 SES4 patients (age 68 ± 13 years, 63% NSTEMI) were included. PCI use was lower in SES1 compared to SES4 in both STEMI (80% vs 84%, p < 0.012) and NSTEMI (42% vs 48%, p < 0.002) patients. Coronary artery bypass grafting was performed more often in SES1 than in SES4 in both STEMI (7% vs 4%, p = NS) and NSTEMI (11% vs 7%, p < 0.001) patients. Optimal medical therapy use in STEMI patients was higher in SES1 compared to SES4 (52% vs 46%, p = 0.01) but comparable among NSTEMI patients (39% vs 40%, p = NS). One-year mortality was comparable in SES1 and SES4 patients following STEMI (14% vs 16%, p = NS) and NSTEMI (10% vs 11%, p = NS). Conclusion: Combined analysis of claims data and area-specific socioeconomic statistics can provide unique insight into how to improve myocardial infarction care for low and high SES patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapeutic treatment in classic Hodgkin lymphoma (CHL) survivors contributes to long-term survival but is associated with lifetime increased risk of cardiovascular events. Echocardiographic screening for left ventricular (LV) dysfunction usually assesses left ventricular ejection fraction (LVEF). Global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The aim of this study was to evaluate the association of conventional echocardiographic parameters and GLS in relation to cardiovascular events in CHL survivors treated with thoracic radiotherapy. Impaired GLS was associated with increased risk of cardiovascular events. In addition, conventional echocardiographic parameters, including LVEF and diastolic dysfunction also showed a significant association with cardiovascular events and cardiac death. Assessing LV strain by echocardiography can contribute to early detection of subclinical LV dysfunction and identifying CHL patients at increased risk for cardiovascular events. Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The purpose of this study was to evaluate if conventional echocardiographic parameters and GLS are associated with cardiovascular events during long-term follow-up. Methods: 161 consecutive CHL patients treated with radiotherapy who underwent echocardiography > 10 years after diagnosis were assessed for eligibility. Multivariable cause-specific Cox regression was performed for a composite outcome of cardiac death and cardiovascular events and the competing outcome of noncardiac death. Results: 129 patients (61.2% female, N = 79) with a mean age of 46.3 ± 11.0 years at index visit were eligible for analysis. GLS was impaired in 51 patients (39.5%) and 10.9% had a LVEF of< 50%. The median E/e' was 9.2 [7.2;12.7]. Adjusted for confounders, GLS > −16% showed a significant association with a near four-fold risk of the composite endpoint (HR = 3.95, 95% CI: 1.83–8.52, p < 0.001). LVEF < 50% (HR = 2.99, p = 0.016) and E/e' (HR = 1.16, p < 0.001) also showed a significant relationship with the outcome. None of the aforementioned parameters were associated with the competing outcome. Conclusions: This study shows that LV dysfunction including impaired GLS in CHL survivors is associated with cardiovascular events and cardiac death. [ABSTRACT FROM AUTHOR]

Background Progressive renal insufficiency is frequent in heart failure patients with a left ventricular assist device (LVAD). The optimal strategy for long-term dialysis in LVAD patients and its effect on quality-of-life in these patients remain to be determined. Case summary Our 55-year-old patient with pre-existing renal insufficiency received an LVAD as destination therapy because of advanced ischaemic heart failure. Six years after implantation, he developed end-stage renal disease for which peritoneal dialysis (PD) was initiated. Left ventricular assist device flow alterations during ultrafiltration did not cause clinical or technical problems. The patient's exercise capacity increased and quality-of-life improved. Over 7.5 years after LVAD implantation and 16 months after PD initiation, he died from encephalitis. Discussion Despite initial improvement, renal function often gradually decreases after LVAD implantation. Data on long-term renal replacement therapy in LVAD patients are limited. Haemodialysis is most commonly applied. Conceptually, however, PD has advantages over haemodialysis including less bloodstream infections, less haemodynamic shifts, and the comfort of the ambulant setting. This case illustrates that PD in an LVAD patient is feasible and improves quality-of-life. Key factors contributing to successful PD in LVAD patients may be a good right ventricular function and close cardiology–nephrology collaboration. [ABSTRACT FROM AUTHOR]

Background Cardiac implanted electronic devices (CIED) have significantly improved the survival and quality of life in heart failure patients. Although implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) have a major role in patients with moderate to severe heart failure symptoms, the role of these devices in patients with a left ventricular assist device (LVAD) is not yet well defined. The burden of CIED-related procedures in patients with an LVAD is high. The price of lead malfunctions and pocket complications requires creative approaches to tackle CIED-related issues in this patient population. Case summary Here, we describe the clinical course of a 67-year-old ventricular pacing dependent LVAD patient with an ICD indication based on recurrent monomorphic ventricular tachycardias and a CRT indication due to previous deterioration of (right-sided) heart failure in the absence of biventricular pacing. We were confronted with impending right ventricular lead failure and bilateral venous access problems due to chronic subclavian vein occlusion in a patient with a total of five transvenous leads, therapeutic anticoagulation, and pronounced thoracic collaterals. We sought for a creative solution to be able to deliver effective biventricular fusion pacing with the existing leads from two contralateral pulse generators resulting in biventricular fusion pacing. This provided the solution to deliver effective CRT. Discussion This case illustrates the complexity of care and CIED-related decision-making in pacing dependent LVAD patients, in particularly those with an ICD and CRT indication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined how the diastolic functions in patients with chronic myocardial ischemia can be affected by intramyocardial bone marrow-derived mononuclear cell injection. Standard echocardiography and strain analysis were used to assess the diastolic function of 50 patients. The study found that the positive effect on myocardial relaxation and filling pressures in chronic myocardial ischemia patients is related to the intramyocardial bone marrow cell injection.

Background: 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. Methods: In 30 patients with chronic ischemia, bone marrow was aspirated from the iliac crest. During mononuclear cell isolation, coronary angiography was performed. Thereafter, 94±18x106 cells were injected intramyocardially (NOGA system) in regions with ischemia on technetium-99m tetrofosmin SPECT. Results: 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 (P<0.01). MRI-determined left ventricular ejection fraction increased from 51±12% to 54±12% at 3 months (P<0.01) and the number of ischemic segments per patient on SPECT decreased from 5.2±2.6 to 2.1±2.2 at 3 months (P<0.01). 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. Conclusion: Intramyocardial bone marrow cell transplantation in patients with chronic myocardial ischemia was not associated with significant progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Heart failure (HF) hospitalisations due to decompensation are associated with shorter life expectancy 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 decompensation may facilitate timely optimisation of the ambulatory medical treatment and thereby prevent heart-failure-related hospitalisations. The HeartLogicTM algorithm combines data from five sensors of cardiac implantable electronic devices into a cumulative index value. It has been developed for early detection of fluid retention in heart failure patients. This review aims to provide an overview of the current literature and experience with the HeartLogicTM algorithm, illustrate how the index can be implemented in daily clinical practice and discuss ongoing studies and potential future developments of interest. [ABSTRACT FROM AUTHOR]

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 (p <0.01) and 2.4 +/- 0.6 after 6 months (p <0.01). The quality-of-life score improved from 52 +/- 10% to 71 +/- 10% at 3 months (p <0.01) to 73 +/- 15% at 6 months (p <0.01). The exercise capacity increased from 79 +/- 31% to 84 +/- 29% (p <0.05). Magnetic resonance imaging revealed an increased LV ejection fraction from 51 +/- 11% to 54 +/- 10% (p <0.01) and a reduced LV end-systolic volume from 97 +/- 50 to 88 +/- 42 ml (p <0.01). The wall motion score index improved from 0.36 +/- 0.32 to 0.24 +/- 0.28 (p <0.01). The number of segments with stress-induced ischemia decreased from 5.1 +/- 3.2 to 2.3 +/- 2.6 (p<0.01). 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. [ABSTRACT FROM AUTHOR]

Background & Aims: Early identification of worsening HF enables timely adjustments to prevent hospitalization. Recent studies show the HeartLogic™ algorithm detects congestion and reduces HF events. However, it is unclear which patients benefit most. Therefore, this study aims to identify and characterize HF patients who benefit most from CIED-based remote monitoring with HeartLogic™., Methods: In this multicenter retrospective study, patients with a CIED and HeartLogic™ algorithm under structured follow-up were included. Patients were classified as having "substantial benefit" or "no benefit" from monitoring., Results: In total, 242 patients were included (male n = 190, 79%, median age 61 years [IQR 61-77]). Median follow-up was 1.2 years [IQR 1.1-2.7]. Among 378 alerts, 266 were true positive (70%) and 112 false positive (30%). Of the 242 patients, 69 (29%) were classified as having "substantial benefit", while 173 (71%) had "no benefit" from HeartLogic™ monitoring. Univariate and multivariate analysis showed that patients with "substantial benefit" had higher NYHA functional class (OR 2.64, P = 0.004), higher NT-ProBNP (OR 1.02, P = 0.003), higher serum creatinine (OR 1.10, P < 0.001), lower LVEF (OR 1.19, P = 0.004), more severe mitral regurgitation (OR 2.16, P = 0.006), higher right ventricular end diastolic volume (OR 1.05, P = 0.040), higher pulmonary artery pressures (OR 1.19, P = 0.003), and were more likely to use loop diuretics (OR 2.79, P = 0.001). Among patients with "substantial benefit," the positive predictive value (PPV) of HeartLogic™ to detect congestion was 92%., Conclusion: The utilization of CIED-based HeartLogic™ driven HF care demonstrated pronounced efficacy, predominantly in patients exhibiting characteristics of HF at a more advanced disease stage., Competing Interests: Declaration of competing interest The department of Cardiology of the LUMC reports receiving unrestricted research and educational grants from Boston Scientific Corporation, Medtronic, and Biotronik. The department of cardiology of OLV Aalst reports receiving research and educational grants from Boston Scientific, Medtronic, Biotronik, Abbott St Jude Medical, and Microport and an educational and research grant from Boston Scientific with reference number ISRRM11793. The funders were not involved in study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. ADE receives consultancy and speaker fees from Boston Scientific Corporation and Medtronic. SLMAB receives speaker fees from Boston Scientific Corporation and Medtronic. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms., Methods: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death., Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers., Methods and Results: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF., Conclusion: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The implantable cardiac defibrillator-based HeartLogic algorithm aims to detect impending fluid retention in patients with heart failure (HF). Studies show that HeartLogic is safe to integrate into clinical practice. The current study investigates whether HeartLogic provides clinical benefit on top of standard care and device telemonitoring in patients with HF., Methods: A multicenter, retrospective, propensity-matched cohort analysis was performed in patients with HF and implantable cardiac defibrillators, and it compared HeartLogic to conventional telemonitoring. The primary endpoint was the number of worsening HF events. Hospitalizations and ambulatory visits due to HF were also evaluated., Results: Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2; IQR 0-4) compared to the HeartLogic group (1; IQR 0-3; P = 0.004). The number of HF hospitalization days was higher in controls than in the HeartLogic group (8; IQR 5-12 vs 5; IQR 2-7; P = 0.023), and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic group (2; IQR 0-3 vs 1; IQR 0-2; P = 0.0001)., Conclusion: Integrating the HeartLogic algorithm in a well-equipped HF care path on top of standard care is associated with fewer worsening HF events and shorter duration of fluid retention-related hospitalizations., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Left ventricular assist device (LVAD) implantation as destination therapy (DT) is a valuable treatment option in patients with end-stage heart failure ineligible for heart transplant. However, this therapy can be complicated by life-threatening pump thrombosis (PT). This case series reports our single-center experience with a structured systemic thrombolysis protocol in case of PT. Consecutive patients undergoing DT LVAD (HVAD, Medtronic, Framingham, MA) implantation between 2010 and April 2021 at our institution were reviewed and those with PT identified. Clinical, laboratory and LVAD specific data were collected and analyzed retrospectively. All patients with PT were treated with systemic thrombolysis according to a structured bedside protocol. Treatment was defined successful if a patient was alive at 30 days follow-up and free of recurrent PT, stroke or device exchange. Fourteen out of 94 patients experienced a PT after LVAD implantation (11%). Systemic thrombolysis was successful in 10 of 14 patients (71%) at 30 days. Two patients died within 30 days due to a hemothorax and multi-organ failure. In three patients treatment was complicated by a major bleeding; twice a hemothorax (one fatal) and one right calf bleeding. No intracerebral hemorrhage was observed. Three patients experienced a thrombotic complication within 30 days; all recurrent PT. Eleven of the 14 DT patients were discharged home after a limited hospital stay after thrombolysis (average of 11 days). In conclusion, systemic thrombolysis may be a reasonable option for life-threatening PT in this vulnerable DT group in whom device exchange is often impossible due to comorbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kortekaas, den Exter, Beeres, Palmen, Jukema, Huisman and Tops.)

Introduction: Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB., Methods and Analysis: This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30., Ethics and Dissemination: The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences., Trial Registration Number: NCT04812717., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Early detection of impending fluid retention and timely adjustment of (medical) therapy can prevent heart failure related hospitalizations. The multisensory cardiac implantable electronic device (CIED) based algorithm HeartLogic TM aims to alert in case of impending fluid retention. The aim of the current analysis is to evaluate the performance of the HeartLogic TM guided heart failure care path in a real-world heart failure population and to investigate whether the height of the index and the duration of the alert state are indicative of the degree of fluid retention., Methods: Consecutive adult heart failure patients with a CIED and an activated HeartLogic TM algorithm were eligible for inclusion. Patients were followed up according to the hospital's heart failure care path. The device technician reviewed alerts for a technical CIED checkup. Afterwards, the heart failure nurse contacted the patient to identify impending fluid retention. An alert was either true positive or false positive. Without an alert a patient was true negative or false negative., Results: Among 107 patients, [82 male, 70 (IQR 60-77) years, left ventricular ejection fraction 37 ± 11%] 130 HeartLogic TM alerts were available for analysis. Median follow up was 14 months [IQR 8-23]. The sensitivity to detect impending fluid retention was 79%, the specificity 88%. The positive predictive was value 71% and the negative predictive value 91%. The unexplained alert rate was 0.23 alerts/patient year and the false negative rate 0.17 alerts/patient year. True positive alerts [42 days (IQR 28-63)] lasted longer than false positive alerts [28 days (IQR 21-44)], p = 0.02. The maximal HeartLogic TM index was higher in true positive alerts [26 (IQR 21-34)] compared to false positive alerts [19 (IQR 17-24)], p < 0.01. Patients with higher HeartLogic TM indexes required more intense treatment (index height in outpatient setting 25 [IQR 20-32], day clinic treatment 28 [IQR 24-36] and hospitalized patients 45 [IQR 35-58], respectively), p < 0.01., Conclusion: The CIED-based HeartLogic TM algorithm facilitates early detection of impending fluid retention and thereby enables clinical action to prevent this at early stage. The current analysis illustrates that higher and persistent alerts are indicative for true positive alerts and higher index values are indicative for more severe fluid retention., Competing Interests: AE is a local sub-investigator for the PREEMPT-HF study. RT, SB, and AE received a speaker's honorarium from Boston Scientific in the past 5 years. The Department of Cardiology reports receiving unrestricted research and educational grants from Boston Scientific Corporation, Medtronic, and Biotronik. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feijen, Egorova, Treskes, Mertens, Jukema, Schalij and Beeres.)

Introduction: Patients with multiple chronic diseases suffer from reduced life expectancy. Care for these patients is often divided over multiple healthcare professionals. eHealth might help to integrate care for these patients and create a continuum. It is the primary purpose of this paper to describe an intervention that integrates first, second, and third line care in patients with multiple chronic conditions using remote monitoring, remote therapy and data automatization, all integrated in a virtual care center (VCC)., Methods: Patients diagnosed with three or more chronic conditions are included and given smartphone compatible devices for remote monitoring and a tablet for video consultations. Patients will be followed-up by the VCC, consisting of nurses who will coordinate care, supervised by general practitioners and medical specialists. Data is reviewed on a daily basis and patients are contacted on a weekly basis. Review of data is automated by computer algorithms. Patients are contacted in case of outcome abnormalities in the data. Patients can contact the VCC at any time. Follow-up of the study is 1 year., Results: The primary outcome of this study is the median number of nights admitted to the hospital per patient compared to the hospitalization data 12 months before enrolment. Secondary outcomes include all-cause mortality, event free survival, quality of life and satisfaction with technology and care., Conclusion: This study presents the concept of a VCC that integrates first, second, and third line care into a virtual ward using remote monitoring and video consultation., Competing Interests: RT reports receiving a speaker's fee from Boston Scientific, Pfizer, and Sanofi within the last 36 months. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van der Lande, Treskes, Beeres and Schalij.)

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 (<5km vs. > 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Janssen, Jukema, Beeres, Schalij and Tops.)

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., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.

Objectives: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology., Design: Retrospective., Setting: University medical center, single institutional., Participants: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015)., Measurements and Main Results: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia., Conclusions: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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/m 2 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., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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 < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter)., Conclusions: Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Over the last decade, much was learned about the biology of several types of stem and progenitor cells. It has become apparent that various cell sources may have the capacity to promote cardiomyogenesis and new blood vessel formation through different mechanisms, forming the rationale for cell-based therapy in patients with chronic ischemic heart disease. After initial clinical studies have provided evidence for safety of cell administration, larger randomized trials demonstrated variable effects on myocardial perfusion and contractile performance. Although cell-based therapy is a promising strategy for the treatment of myocardial disease, many questions remain to be answered with respect to the optimal cell type, delivery route and mechanism of action in order to improve the outcome of cardiac cell therapy. This paper aims to provide an overview of the methods available to apply cell-based therapy in chronic ischemic myocardial disease. The different cell types that have been tested in (pre)clinical trials and their proposed mechanism of action will be discussed, along with the possible routes of cell delivery. Furthermore, the experience from experimental and clinical studies will be summarized, and innovative strategies to enhance the efficacy of cell therapy, for example by improving cell retention and survival, will be reviewed.

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 x 10(6) 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., ((c) 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 (p <0.01) and 2.9 +/- 0.8 at 6 months (p <0.01 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, p <0.01) 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.