Sleep - the yet underappreciated player in cardiovascular diseases: A clinical review from the German Cardiac Society Working Group on Sleep Disordered Breathing.

Patients with a wide variety of cardiovascular diseases, including arterial and pulmonary hypertension, arrhythmia, coronary artery disease and heart failure, are more likely to report impaired sleep with reduced sleep duration and quality, and also, sometimes, sleep interruptions because of paroxysmal nocturnal dyspnoea or arrhythmias. Overall, objective short sleep and bad sleep quality (non-restorative sleep) and subjective long sleep duration are clearly associated with major cardiovascular diseases and fatal cardiovascular outcomes. Sleep apnoea, either obstructive or central in origin, represents the most prevalent, but only one, of many sleep-related disorders in cardiovascular patients. However, observations suggest a bidirectional relationship between sleep and cardiovascular diseases that may go beyond what can be explained based on concomitant sleep-related disorders as confounding factors. This makes sleep itself a modifiable treatment target. Therefore, this article reviews the available literature on the association of sleep with cardiovascular diseases, and discusses potential pathophysiological mechanisms. In addition, important limitations of the current assessment, quantification and interpretation of sleep in patients with cardiovascular disease, along with a discussion of suitable study designs to address future research questions and clinical implications are highlighted. There are only a few randomised controlled interventional outcome trials in this field, and some of the largest studies have failed to demonstrate improved survival with treatment (with worse outcomes in some cases). In contrast, some recent pilot studies have shown a benefit of treatment in selected patients with underlying cardiovascular diseases.

Capacitive ECG Monitoring in Cardiac Patients During Simulated Driving.

OBJECTIVE: This study aims to compare the informative value of a capacitively coupled electrocardiogram (cECG) to a conventional galvanic reference ECG (rECG) in patients after a major cardiac event under simulated driving conditions. Addressed research questions are the comparison and coherence of cECG and rECG by means of the signal quality, the artifact rate, the rate of assessable data for differential diagnosis, the visibility of characteristic ECG structures in cECG, the precision of ECG time intervals, and heart rate (in particular, despite possible waveform deformations due to the cardiac preconditions). METHODS: In a clinical trial, cECG and rECG data were recorded from ten patients after a major cardiac event. The cECG and rECG data were blindly evaluated by two cardiologists with regard to signal quality, artifacts, assessable data for differential diagnosis, visibility of ECG structures, and ECG time intervals. The results were statistically compared. RESULTS: The cECG presented with more artifacts, an inferior signal quality, and less assessable data. However, when the data were assessable, determination of the ECG interval lengths was coherent to the one obtained from the rECG. CONCLUSION: When the signal quality is sufficient, the cECG yields the same informative value as the rECG. SIGNIFICANCE: For certain scenarios, cECG might replace rECG systems. Hence, it is an important research question whether a similar amount of information can be obtained using a cECG system.

An m-Health system for education and motivation in cardiac rehabilitation: the experience of HeartCycle guided exercise.

Introduction Home-based programmes for cardiac rehabilitation play a key role in the recovery of patients with coronary artery disease. However, their necessary educational and motivational components have been rarely implemented with the help of modern mobile technologies. We developed a mobile health system designed for motivating patients to adhere to their rehabilitation programme by providing exercise monitoring, guidance, motivational feedback, and educational content. Methods Our multi-disciplinary approach is based on mapping "desired behaviours" into specific system's specifications, borrowing concepts from Fogg's Persuasive Systems Design principles. A randomised controlled trial was conducted to compare mobile-based rehabilitation (55 patients) versus standard care (63 patients). Results Some technical issues related to connectivity, usability and exercise sessions interrupted by safety algorithms affected the trial. For those who completed the rehabilitation (19 of 55), results show high levels of both user acceptance and perceived usefulness. Adherence in terms of started exercise sessions was high, but not in terms of total time of performed exercise or drop-outs. Educational level about heart-related health improved more in the intervention group than the control. Exercise habits at 6 months follow-up also improved, although without statistical significance. Discussion Results indicate that the adopted design methodology is promising for creating applications that help improve education and foster better exercise habits, but further studies would be needed to confirm these indications.

Internet-based training of coronary artery patients: the Heart Cycle Trial.

Low adherence to cardiac rehabilitation (CR) might be improved by remote monitoring systems that can be used to motivate and supervise patients and tailor CR safely and effectively to their needs. The main objective of this study was to evaluate the feasibility of a smartphone-guided training system (GEX) and whether it could improve exercise capacity compared to CR delivered by conventional methods for patients with coronary artery disease (CAD). A prospective, randomized, international, multi-center study comparing CR delivered by conventional means (CG) or by remote monitoring (IG) using a new training steering/feedback tool (GEx System). This consisted of a sensor monitoring breathing rate and the electrocardiogram that transmitted information on training intensity, arrhythmias and adherence to training prescriptions, wirelessly via the internet, to a medical team that provided feedback and adjusted training prescriptions. Exercise capacity was evaluated prior to and 6 months after intervention. 118 patients (58 ± 10 years, 105 men) with CAD referred for CR were randomized (IG: n = 55, CG: n = 63). However, 15 patients (27 %) in the IG and 18 (29 %) in the CG withdrew participation and technical problems prevented a further 21 patients (38 %) in the IG from participating. No training-related complications occurred. For those who completed the study, peak VO2 improved more (p = 0.005) in the IG (1.76 ± 4.1 ml/min/kg) compared to CG (-0.4 ± 2.7 ml/min/kg). A newly designed system for home-based CR appears feasible, safe and improves exercise capacity compared to national CR. Technical problems reflected the complexity of applying remote monitoring solutions at an international level.

Impact of SERVE-HF on management of sleep disordered breathing in heart failure: a call for further studies.

Sleep disordered breathing (SDB) (obstructive sleep apnea, central sleep apnea/Cheyne-Stokes respiration or the combination of both) is highly prevalent in patients with a wide variety of cardiovascular diseases including hypertension, arrhythmia, coronary artery disease, myocardial infarction and stroke (reviewed previously in the September issue of this journal). Its close association with outcomes in chronic heart failure with reduced ejection fraction (HF-REF) suggests that it may be a potential treatment target. Herein, we provide an update on SDB and its treatment in HF-REF.

Trauma and syncope-evidence for further sleep study? A case report.

We report on an 83-year-old male with traumatic brain injury after syncope with a fall in the morning. He had a history of seizures, coronary artery disease and paroxysmal atrial fibrillation (AF). No medical cause for seizures and syncope was determined. During rehabilitation, the patient still complained of seizures, and also reported sleepiness and snoring. Sleep apnea diagnostics revealed obstructive sleep apnea (SA) with an apnea-hypopnoea index of 35/h, and sudden onset of tachycardia with variations of heart rate based on paroxysmal atrial fibrillation. Additional tests showed nocturnal AF which spontaneously converted to sinus rhythm mid-morning with an arrest of 5 s (sick sinus syndrome) and seizures. A DDD-pacer was implanted and no further seizures occurred. SA therapy with nasal continuous positive airway pressure was refused by the patient. Our findings suggests that screening for SA may offer the possibility to reveal causes of syncope and may introduce additional therapeutic options as arrhythmia and SA often occur together which in turn might be responsible for trauma due to syncope episodes.

Capacitive ECG recording and beat-to-beat interval estimation after major cardiac event.

Today, heart diseases are the most common cause of death in the U.S.. Due to improved healthcare, more and more patients survive a major cardiac event, e.g. a heart attack. However, participation in everyday activity (e.g. driving a car) can be impaired afterwards. Patients might benefit from heart activity monitoring while driving using a capacitive ECG (cECG). However, it is unknown whether cECG is an appropriate monitoring tool for such patients. In this work, first results from a study including 10 patients having survived at least one major cardiac event are presented. It is shown that cECG can be used to diagnose heart rhythm deviations and estimate beat-to-beat intervals similar to conventional ECG.

Risk factors for, and prevalence of, sleep apnoea in cardiac rehabilitation facilities in Germany: The Reha-Sleep registry.

AIM: To determine the prevalence of, and the risk factors for, sleep apnoea in cardiac rehabilitation (CR) facilities in Germany. METHODS: 1152 patients presenting for CR were screened for sleep-disordered breathing with 2-channel polygraphy (ApneaLink™; ResMed). Parameters recorded included the apnoea-hypopnoea index (AHI), number of desaturations per hour of recording (ODI), mean and minimum nocturnal oxygen saturation and number of snoring episodes. Patients rated subjective sleep quality on a scale from 1 (poor) to 10 (best) and completed the Epworth Sleepiness Scale (ESS). RESULTS: Clinically significant sleep apnoea (AHI ≥15/h) was documented in 33% of patients. Mean AHI was 14 ± 16/h (range 0-106/h). Sleep apnoea was defined as being of moderate severity in 18% of patients (AHI ≥15-29/h) and severe in 15% (AHI ≥30/h). There were small, but statistically significant, differences in ESS score and subjective sleep quality between patients with and without sleep apnoea. Logistic regression model analysis identified the following as risk factors for sleep apnoea in CR patients: age (per 10 years) (odds ratio (OR) 1.51; p<0.001), body mass index (per 5 units) (OR 1.31; p=0.001), male gender (OR 2.19; p<0.001), type 2 diabetes mellitus (OR 1.45; p=0.040), haemoglobin level (OR 0.91; p=0.012) and witnessed apnoeas (OR 1.99; p<0.001). CONCLUSIONS: The findings of this study indicate that more than one-third of patients undergoing cardiac rehabilitation in Germany have sleep apnoea, with one-third having moderate-to-severe SDB that requires further evaluation or intervention. Inclusion of sleep apnoea screening as part of cardiac rehabilitation appears to be appropriate.

Evaluation of a newly designed shirt-based ECG and breathing sensor for home-based training as part of cardiac rehabilitation for coronary artery disease.

BACKGROUND: Participation in phase-III cardiac rehabilitation (CR) remains low but adherence could potentially be improved with supervised home-based CR. New technological approaches are needed to provide sufficient supervision with respect to safety and performance of individual exercise programmes. DESIGN: The newly designed closed-loop tool, HeartCycle's guided exercise (GEX) system, will support professionals and patients during exercise-based CR. Patients wear a dedicated shirt with incorporated wireless sensors, and ECG, heart rate (HR), breathing frequency (BF), and activity are monitored during exercise. This information is streamed live to a mobile device (PDA) that processes these parameters. METHODS: A phase-I study was performed to evaluate feasibility, function, and reliability of this GEX device and compare it to conventional cardiac exercise testing (CPX, spiroergometry) in 50 patients (seven women, mean ± SD age 69 ± 9 years, body mass index 26 ± 3 kg/m(2), ejection fraction 58 ± 10%). ECG, HR, and BF were monitored using standard equipment and the GEX device simultaneously. Furthermore, HR recorded on the PDA was compared with CPX measurements. RESULTS: The fit of the shirt and the sensor was good. No technical problems were encountered. All occurring arrhythmia were reliably detected. There was an acceptable comparability between HR on the GEX device vs. CPX, a good comparability between HR on the PDA vs. CPX, and a moderate comparability between BF on the GEX device vs. CPX CONCLUSIONS: Comparability between CPX and the GEX device was acceptable for HR measurement and moderate for BF; arrhythmias were reliably detected. HR processing and display on the PDA was even better comparable. The whole system seems suitable for monitoring home-based CR. Further studies are now needed to implement training prescription to facilitate individual exercise.

Poor sleep quality is associated with depressive symptoms in patients with heart disease.

BACKGROUND: Depression in cardiac patients has gained importance due to increased mortality. Although sleep disturbances are a core symptom of depression, the prevalence and patterns of sleep disturbances in heart disease have hardly been examined regarding depression. PURPOSE: This cross-sectional study aims to examine sleep disturbances and depressive symptoms in consecutively admitted cardiac patients and depressed patients. METHODS: Two hundred four inpatients (113 male, 91 female) were examined: 94 cardiac inpatients (mean age 49.3 ± 14.3 years) with different heart diseases and 110 psychiatric inpatients (mean age 41.6 ± 13.0 years) with depressive disorders (DP). A depressive episode according to International Classification of Diseases (ICD)-10 was also diagnosed in 14 of the cardiac patients (DCP). The Pittsburgh Sleep Quality Index (PSQI) and the Beck Depression Inventory (BDI) were used to assess subjective sleep quality and severity of depressive symptoms. RESULTS: Poor sleep quality (PSQI > 5) was reported in all comorbid DCP (PSQI 12.00 ± 3.53, BDI 17.86 ± 4.28), in 60% of the 80 non-DCP (PSQI 5.59 ± 3.73, BDI 4.47 ± 3.07), and in 86.4% of the DP (PSQI 11.76 ± 4.77, BDI 27.11 ± 10.54). The cardiac inpatients showed a significant correlation between increased depressive symptoms and the PSQI components subjective sleep quality (r = 0.40) and daytime dysfunction (r = 0.34). Both sleep components were significant predictors of self-rated depression (R² = 0.404). CONCLUSIONS: Most cardiac patients experience poor sleep quality. Self-reported sleep disturbances in heart disease could serve as predictors of clinical or subclinical comorbid depression outside of a psychiatric setting in cardiology and other fields, and such patients should be referred to consultation-liaison psychiatry or polysomnography where sleep disorders like sleep apnea are suspected.

Application of zinc-bis-(DL-hydrogensaspartate) does not reduce apoptotic cell death in myocardial infarction in the rat heart.

BACKGROUND: Early studies in different stress models have shown potential beneficial effects of exogenous zinc application with reduction in the rate of apoptotic cell death. This has not been shown in models of myocardial infarction. METHODS: Rats were exposed to either brief episodes of acute ischemia followed by reperfusion (phase 1) or chronic coronary occlusion (phase 2). Animals were either treated with zinc or vehicle. Groups 1 and 3 received zinc-bis-(DL-hydrogenaspartate) 10 mg/kg body weight as a single 5-mL bolus administered intraperitoneally 24 hours prior to coronary occlusion, groups 2 and 4 received saline. The infarct sizes were determined by triphenyltetrazolium chloride staining and expressed at relative areas to areas of ischemia. Histological slices of the rat's myocardium at the border zones of the infarcts were stained with the TUNEL method to assess for apoptosis. Animals in groups 5, 7, and 9 received zinc, given once before and then repeated every 4 days after coronary occlusion, whereas groups 6, 8, and 10 received saline. Animals were observed for observation periods of 13 (groups 9 and 10), 16 (groups 7 and 8), or 19 weeks (groups 5 and 6), respectively. Two-dimensional echocardiography was performed to measure ejection fraction (EF) at baseline and at the end of the observation periods. TUNEL staining was used to detect and quantify apoptosis rate in the border zones of infarcts after the hearts were excised. RESULTS: Infarct sizes were 49% + 22% in group 1 (zinc + 30 minutes ischemia + 30 minutes reperfusion); 48% + 10% in group 2 (vehicle + 30 minutes ischemia + 30 minutes reperfusion); 42% + 11% in group 3 (zinc + 60 minutes ischemia + 30 minutes reperfusion); and 41% + 23% in group 4 (vehicle + 60 minutes ischemia + 60 minutes reperfusion). In group 1, 11% + 6% of cells were apoptotic compared to 12% + 4% in group 2, 16% + 9% in group 3, and 17% + 7% in group 4 (P > .05). In phase 2, echocardiography revealed a significant reduction in EF in all groups after coronary occlusion. There were no significant differences in EF between the 5 groups at baseline and at follow-up. TUNEL staining did not reveal any significant apoptosis after 13 to 19 weeks. CONCLUSION: Application of zinc failed to result in reduction of infarct size after temporary coronary occlusion followed by reperfusion and did not demonstrate any reduction in apoptotic cell death. In chronic coronary occlusion, zinc also did not improve EF compared to controls in the presented model in rats. The mechanisms involved in antiapoptotic effects seem to be more complex and might not be inducible by simple zinc injections.

Effect of cardiac resynchronization therapy on sleep quality, quality of life, and symptomatic depression in patients with chronic heart failure and Cheyne-Stokes respiration.

Patients with heart failure (HF) often suffer from sleep-related breathing disorders (SRBD) like Cheyne-Stokes respiration (CSR). Cardiac resynchronization therapy (CRT) improves myocardial function and exercise capacity in patients with HF and conduction disturbances. As CRT has been shown to reduce CSR in patients with HF, it is not clear whether CRT improves quality of life and symptomatic depression by improvement of apnea/hypopnea index (AHI) and sleep quality. Forty-two HF patients with conduction disturbance before CRT were screened for CSR and evaluated for sleep quality [Pittsburgh Sleep Quality Index (PSQI)], quality of life score [36-item short form (SF-36)], depression, and exercise capacity (VO2 peak) and ejection fraction (EF). Eighteen patients (three females, age 61+/-10, body mass index 24+/-4 kg m(-2), EF 24+/-4%, QRS complex duration 156+/-32 ms) presented CSR with an AHI of 18+/-8 (11 CSR, 7 mixed). Fourteen patients showed no SRBD (PSQI<5,AHI<5). All patients received CRT and were reevaluated after 18+/-7 weeks. CSR worsen quality of life in seven of eight terms compared to patients without SRBD. Symptomatic depressive symptoms (Beck Depression Inventory>10) were only present in patients with CSR. CRT results in improvement of peak VO2 and EF. There was no difference between patients with CSR and without SRBD on exercise capacity or EF under CRT, whereas CRT led to a significant decrease in AHI (18+/-8 to 3+/-2, p<0.0001), PSQI (18+/-4 to 6+/-3, p=0.0007), with reduction of depression score (12+/-3 to 4.8+/-3, p=0.004). In patients with HF, CSR is associated with symptomatic depressive syndromes and impaired quality of life. CRT reduced CSR with improvement of sleep quality and symptomatic depression.

Comparison of the 6-minute walk test with established parameters for assessment of cardiopulmonary capacity in adults with complex congenital cardiac disease.

BACKGROUND: Objective assessment of the cardiopulmonary capacity in patients with complex congenital cardiac disease often remains difficult in clinical practice. The cardiopulmonary exercise test and determination of the levels of brain natriuretic peptide in the plasma are established tests, but expensive. The 6-minute walk test is also validated, but has not often been used in patients with heart failure due to congenital heart disease, nor compared with other tests. We sought to compare its value with the results of cardiopulmonary exercise testing and measuring the levels of brain natriuretic peptide in the plasma. METHODS: We carried out a standardized 6-minute walk test in 31 patients with complex congenital cardiac disease on the same day that they underwent cardiopulmonary exercise testing and determination of levels of brain natriuretic peptide in the plasma. Of the patients, 7 had functionally univentricular hearts, 9 had transposition, 9 had tetralogy of Fallot, 3 had common arterial trunk, and 3 had pulmonary atresia with intact interventricular septum. Uptakes of oxygen at peak exercise, and at the anaerobic threshold, were determined using cardiopulmonary exercise testing, and classified as suggested by Weber. The 6-minute walk test was performed according to a standard protocol. RESULTS: There was a significant correlation between brain natriuretic peptide, oxygen uptakes at peak exercise and 6-minute walk. The correlation between the 6-minute walk test and oxygen uptakes at the anaerobic threshold, however, was not significant. CONCLUSIONS: The 6-minute walk test can be performed easily, is inexpensive, widely available, and correlates well with measurements of brain natriuretic peptide and cardiopulmonary exercise testing, even in patients with corrected or palliated congenital cardiac malformations. A cut-off value of 450 metres in the 6-minute walk test allows a semi-quantitative classification in analogy to the classification suggested by Weber for cardiopulmonary exercise testing, and to a level of brain natriuretic peptide in the plasma of less or more than 100 picograms per millilitre.

Impact of sleep-related breathing disorders on health-related quality of life in patients with chronic heart failure.

BACKGROUND: Quality of life in patients with chronic heart failure (HF) is often severely compromised. Sleep-related breathing disorders (SRBD) like Cheyne-Stokes Respiration (CSR) or obstructive sleep apnea (OSAS) are often observed in patients with severe HF resulting in fragmentation of sleep, excessive daytime sleepiness and an increased mortality. While an apnea/hypopnea-index (AHI) >30/h represents an independent predictor of poor prognosis, clinical relevance of even minor SRBD with an AHI <30/h remains unclear with respect to quality of life, exercise capacity or depression rate. METHODS: Sixty-nine consecutive ambulatory patients with stable HF (NYHA II-III, EF 25%) underwent two night polygraphies with a six-channel ambulatory recording. Spiroergometry was performed, and patients were examined for sleep quality (PSQI), depressed mood (BDI) and health-related quality of life (SF-36). The data were compared to 10 age-matched healthy controls and 11 patients with OSAS (AHI 14-29/h) not suffering from HF. RESULTS: Fifty-one patients completed follow up. 52% were positively diagnosed for SRBD (AHI 16-30/h: 12 patients CSR, 5 patients OSAS, 9 patients mixed); 25 patients (48%) showed no relevant SRBD. Patients with HF and SRBD had lower quality of life than patients without SRBD and HF. The severity of SRBD as indicated by the AHI significantly correlated with quality of life measures: Bodily pain, physical functioning and social functioning showed largest impairment in patients with HF and SRBD. Furthermore, elevated depression rates in correlation to the AHI were only observed in patients with SRBD similar to patients with OSAS without HF. CONCLUSION: Even minor SRBD in patients with HF independently influence quality of life and correlate with estimation of depression and sleep disturbances.

Transplantation of human umbilical vein endothelial cells improves left ventricular function in a rat model of myocardial infarction.

INTRODUCTION: Although cell-based therapy after myocardial infarction (MI) may be beneficial in improving cardiac dysfunction, the underlying mechanisms remain to be clarified. Since human umbilical vein endothelial cells (HUVEC) harbor the potential for transdifferentiation, we studied the functional effects of HUVEC transplantation in a rat model of MI. METHODS AND RESULTS: HUVEC labeled with BrdU or medium alone were injected into the infarcted area and its margin 4 weeks after ligation of the left coronary artery in cyclosporine-treated rats. BrdU(+) signals could be detected in the area of MI at two weeks and two months after injection only in hearts transplanted with HUVEC. While no signs of transdifferentiation into cardiomyocytes were evident, staining for the rat macrophage marker ED-1, adjacent to or colocalized with BrdU(+) signals, revealed an in.ltration with macrophages and implied the phagocytosis of injected HUVEC. In the vicinity of BrdU(+) signals, the density of CD31(+) microvessels was significantly increased in HUVEC-transplanted as compared to medium-treated hearts after two months. HUVEC transplantation led to improved contractility as assessed by echocardiography and to higher coronary flow rates as well as to improved response to volume strain and catecholamine stress in Langendorff perfused hearts. CONCLUSIONS: After MI, transplanted HUVEC persist in the host myocardium and trigger an infiltration with macrophages. The ensuing increase in neovascularization and improvement in global left ventricular function may be attributable to the associated inflammatory response.

Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure.

OBJECTIVES: We studied the effects of cardiac resynchronization therapy (CRT) on heart failure (HF) patients with central sleep apnea (CSA). BACKGROUND: Patients with advanced HF often suffer from CSA with Cheyne-Stokes respiration. Cardiac resynchronization therapy improves myocardial function and exercise capacity in HF patients with conduction disturbances. The relationship between CRT and CSA is currently unknown. METHODS: Twenty-four patients (7 females; 62 +/- 11 years) with HF, a reduced left ventricular ejection fraction (24 +/- 6%), and left bundle branch block (QRS duration 173 +/- 22 ms) received a CRT device. The number of apneas and hypopneas per hour (apnea-hypopnea index [AHI]) and minimal oxygen saturation (SaO2min) were quantified by cardiorespiratory polygraphy. Fourteen patients showed CSA (AHI >5/h), and 10 patients had an AHI <5/h without CSA. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were evaluated before and after 17 +/- 7 weeks of CRT. RESULTS: In patients with CSA, CRT led to a significant decrease in AHI (19.2 +/- 10.3 to 4.6 +/- 4.4, p < 0.001) and PSQI (10.4 +/- 1.6 to 3.9 +/- 2.4, p < 0.001) without Cheyne-Stokes respiration and to a significant increase in SaO2min (84 +/- 5% to 89 +/- 2%, p < 0.001). There was no significant change in AHI (1.7 +/- 0.7 to 1.5 +/- 1.6), PSQI (2.4 +/- 0.5 to 2.6 +/- 0.9), and SaO2min (90 +/- 2% to 91 +/- 1%) in patients without CSA. CONCLUSIONS: Cardiac resynchronization therapy leads to a reduction of CSA and to increased sleep quality in patients with HF and sleep-related breathing disorders. This may have prognostic implications in patients receiving CRT.

Transplantation of fetal cardiomyocytes into infarcted rat hearts results in long-term functional improvement.

Studies have demonstrated the feasibility of transplanting cardiomyocytes after myocardial infarction (MI). However, persistence and effects on left ventricular (LV) function have not been elucidated in long-term studies. Ventricular fetal cardiomyocytes from embryos of both sexes were injected into marginal regions of MI 4 weeks after suture occlusion of the left anterior descending artery in adult female rats. Two and 6 months after transplantation (Tx), engrafted cells were traced by immunohistochemical in situ hybridization for Y chromosomes or bromodeoxyuridine (BrdU) staining, LV dimensions and function were assessed by echocardiography, and LV pressure was assessed ex vivo in a Langendorff perfusion system. Immunohistochemistry for alpha-sarcomeric actin and Y chromosomes revealed the presence of transplanted cells in infarcted host myocardium at both 2 and 6 months. End-diastolic LV diameter markedly decreased after Tx and fractional shortening gradually increased after Tx (31.3 +/- 4.5% before Tx, 45.4 +/- 4.2% at 6 months; p<0.005). Wall area fraction and MI size were unaffected by Tx. In hearts with MI, but not in normal hearts, Tx led to the development of higher pressures (87 +/- 18 versus 38 +/- 8 mmHg, 6 months post-Tx versus nontreated). After catecholamine stimulation, both infarcted and normal hearts developed higher pressures after Tx (p<0.005), ultimately associated with reduced mortality after Tx versus nontreated. Transplanted cardiomyocyte-rich graft cells persist in host myocardium and mediate continuous improvement of LV function and survival in a rat model of MI even during long-term follow-up, possibly involving a catecholamine-sensitive mechanism.