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Cardiac MRI in the isolated porcine heart reveals possible etiology of sudden right heart failure following heart transplantation.

Occurrence of immediate post-transplant heart failure in the cardiac transplant recipient is typically attributed to elevated pulmonary vascular resistance, however other etiologies may play a role. At the completion of the transplant, free air, which has collected in the donor heart, is vented via an aortotomy. Free air may rise into the right coronary artery and obstruct reperfusion of the right ventricle. Cardiac perfusion MRI may offer a method of non-invasively determining the presence of air embolus. The objectives in the pilot study were to identify steps in the donor process where free air could enter into the aortic root causing obstruction of perfusion of the coronary arteries. A change in surgical technique could then be used to eliminate a portal of entry and cardiac perfusion MRI could validate the technique. Standard cardiectomy was compared to a variation in technique in two animals. Pulmonary vein ligation was completed in the experimental model before completion of cardiectomy. Both hearts were isolated and imaged using T1-weighted FLASH sequence and gadolinium contrast via the aortic root. Cardiac perfusion MRI imaging of the heart with the unligated pulmonary vein revealed evidence of air embolus and no perfusion of the right coronary artery compared to the ligated heart. Anatomically, the right coronary artery is anterior in the mediastinum compared to the left coronary artery. Air emboli preferentially rise into the right coronary and can obstruct flow into the right heart. Cardiac perfusion MRI offers an effective method to evaluate the isolated pre-transplant heart for perfusion defects.

Animals↗

The Euro Heart Failure Survey of the EUROHEART survey programme. A survey on the quality of care among patients with heart failure in Europe. The Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The Medicines Evaluation Group Centre for Health Economics University of York.

BACKGROUND: The EUROHEART programme is a rolling programme of cardiovascular surveys among the member nations of the European Society of Cardiology (ESC). These surveys will provide information on the nature of cardiovascular disease and its management. This manuscript describes a survey into the nature and management of heart failure. AIMS: The EuroHeart Failure survey aims to describe the quality of hospital care, diagnostic and therapeutic, for patients with suspected or confirmed heart failure in ESC member countries. Patients will be interviewed subsequent to hospital discharge to assess their understanding of their condition, side effects from and their compliance with therapy and their satisfaction with the management for heart failure. The quality of management will be judged against the recommendations contained in the ESC guidelines on diagnosis and treatment of heart failure. Outcome will be further assessed by repeat interviews in 6-12 months time. A further survey of heart failure in 2001/2002 is also planned. METHODS: A prospective survey of all deaths and discharges from medical (cardiology, internal medicine and geriatric medicine) and cardiac surgical wards to identify patients with heart failure, suspected or confirmed. Approximately 70 hospital clusters, comprising two to six hospitals in each cluster, in 24 member countries of the ESC are conducting the study. At the time of writing, approximately 30000 deaths and discharges have been screened and approximately 4000 patients have been enrolled. CONCLUSIONS: The EuroHeart Survey will allow actual practice to be compared to ESC guidelines on the diagnosis and treatment of heart failure. The surveys and guidelines should prove mutually informative. The main EuroHeart Failure project will be completed by late 2000. However, new centres volunteering to participate in the study (contact corresponding author) may be accepted providing they have the necessary research personnel and provided funding can be agreed for statistical support and administration.

Angiotensin-Converting Enzyme Inhibitors↗

Relationship between heart rate turbulence and heart rate, heart rate variability, and number of ventricular premature beats in coronary patients.

INTRODUCTION: Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters. METHODS AND RESULTS: In 146 patients (117 males and 29 females; mean age 62 years) with coronary artery disease, a 24-hour ECG Holter monitoring was performed to calculate mean heart rate (RR interval), number of VPBs, time- and frequency-domain HRV parameters and two HRT parameters: turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate regression analyses were performed to evaluate the association between tested parameters. Significant correlation between TS and mean RR interval was observed (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS values were significantly higher in patients with less than 10 VPBs/24 hours than in patients with more frequent VPBs. Significant associations between HRT and HRV parameters were found with TS showing stronger correlation with HRV parameters than TO (r value ranging from 0.35 to 0.62 for TS vs. -0.16 to -0.38 for TO). CONCLUSION: HRT parameters correlate strongly with HRV parameters indicating that HRT should be considered as a reflection of both baroreceptors response and overall autonomic tone. Heart rate dependence of turbulence slope indicates the need to adjust this parameter for heart rate.

Coronary Disease↗

Myocardial (iso)enzyme activities, DNA concentration and nuclear polyploidy in hearts of patients operated upon for congenital heart disease, and in normal and hypertrophic adult human hearts at autopsy.

To investigate biochemical characteristics of hypertrophic myocardium of young and adult humans, we analysed myocardial biopsies obtained from 28 mainly young patients undergoing cardiac surgery for congenital heart disease and 41 autopsied hearts from 18 adult normal and 23 hypertrophic human subjects. Myocardial activities of the enzymes creatine kinase and lactate dehydrogenase were independent of age during childhood, but decreased significantly with hypertrophy at adult age. Myocyte nuclei showed increased polyploidization during childhood which was progressive with age, and in the adult stage polyploidization was correlated with heart weight. Nevertheless myocardial DNA concentration fell under both conditions, which is to be ascribed to the 'diluting' effect of myocyte hypertrophy. Before an age of 8 years DNA concentration in the child heart material studied has reached the value found in adult nonhypertrophic hearts, although at that time polyploidization of myocyte nuclei in child hearts was only half the value found in adult non-hypertrophic hearts. Biochemical measurement of DNA concentration in peroperatively taken myocardial biopsies may contribute to the in vivo diagnosis of ventricular hypertrophy in quantitative terms, in combination with radiology, echocardiography and histology.

Adolescent↗

Heart rate and heart rate variability in acute coronary heart disease.

The parameters of cardiac autonomic function, heart period length and heart period length variability were investigated in 70 patients, 50 males and 20 females, mean age 54.8 +/- 9.6 years, admitted to coronary care unit. There were 15 unstable angina patients, 21 anterior wall infarction patients, 20 posterior wall infarction patients, and 14 non-Q-wave infarction patients, who survived to discharge. Heart period length and heart period length variability for each patient were manually measured on the basis of 30 consecutive sinus normal-to-normal RR intervals in ECG every 20 minutes during the initial 24 hours of their stay at the coronary care unit and in the third week after admission. For each interval analyzed, the mean duration of RR interval was computed. RR interval variations were expressed as coefficient of variation (CV). On admission, heart rate was significantly slower (848 +/- 173 ms vs. 837 +/- 163 ms) and CV significantly lower (4.8 +/- 4.2 vs. 5.0 +/- 3.4%) than on discharge (p < 0.01). The significant difference in the mean RR interval between anterior wall infarction patients (802 +/- 186 ms) and inferior wall infarction patients (879 +/- 181 ms) recorded on admission disappeared on discharge from hospital (806 +/- 144 vs. 783 +/- 100 ms). CV was lower in acute myocardial infarction patients (4.7 +/- 3.6; 4.1 +/- 3.2) than in unstable angina patients (5.3 +/- 5.6) on admission (p < 0.05). Heart rate variability was greater in anterior wall infarction patients and unstable angina patients (CV = 5.3 +/- 3.1; 5.2 +/- 3.6%) than in posterior wall infarction patients and non-Q-wave infarction patients (CV = 4.7 +/- 3.5; 4.8 +/- 3.6%). The findings showed that different degrees of cardiac sympathovagal activity may occur in acute coronary heart disease patients during the first 24 hours of their stay at coronary care unit and on discharge from hospital.

Adult↗

No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure.

Speculations about development of tolerance to the inotropic effect of digitalis have been engendered since studies in various in vitro systems and tissues not representative of the heart have shown up-regulation of sodium potassium adenosine triphosphatase (Na,K-ATPase) when exposed to digitalis. Moreover the digitalis receptor (i.e., Na,K-ATPase) concentration in the normal, vital human left ventricle has not been previously determined. On this basis, digitalis receptor concentration was quantified in the left ventricle of explanted hearts from subjects without heart disease and from patients with end-stage heart failure who had received digitalis therapy. This was performed using vanadate-facilitated 3H-ouabain binding to intact tissue samples giving values of 728 +/- 58 (n = 5) and 467 +/- 55 pmol/g wet weight (n = 6) (mean +/- SEM) (p < 0.005), respectively. However, some of the digitalis receptors may have retained digoxin before 3H-ouabain binding and thus may have escaped detection. To eliminate this effect of retained digoxin, samples were exposed to prolonged washing in buffer containing excess digoxin antibody, a method recently shown to clear digoxin from receptors and allow subsequent complete digitalis receptor quantification by 3H-ouabain binding. After washing in digoxin specific antibody, specific digitalis receptor concentration was 760 +/- 58 pmol/g (n = 5) and 614 +/- 47 pmol/g (n = 6) wet weight in samples of the normal and failing hearts, respectively (p < 0.08). Thus, digitalization was associated with occupancy of digitalis receptors in the failing human heart of 24% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Total support of the circulation of a patient with post-cardiotomy stone-heart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation.

A patient with acute bacterial endocarditis in whom ischaemic contracture of the left ventricle (stone-heart syndrome) developed during aortic and mitral valve replacement had an emergency implantation of an intracorporeal partial artificial heart (an abdominal left-ventricular assist device of ALVAD). This device functioned as a total artificial heart for nearly 6 days, while a donor heart for transplantation was sought. The ALVAD was then removed, and the patient received allografts of a heart and a kidney. The transplanted heart functioned well, but the patient died 15 days later from gram-negative sepsis. There was no evidence of cardiac or renal allograft rejection.

Acute Disease↗

Alterations of heart rate and of heart rate variability after radiofrequency catheter ablation of supraventricular tachycardia. Delineation of parasympathetic pathways in the human heart.

BACKGROUND: Persistent inappropriate sinus tachycardia has been reported as a complication after radiofrequency (RF) ablation of the fast atrioventricular (AV) nodal pathway. The purpose of this study was to evaluate the prevalence of this complication and its mechanism using heart rate variability analysis. METHODS AND RESULTS: Time and frequency domain analysis of heart rate was performed in the electrophysiology laboratory immediately before and immediately after RF ablation in 64 patients with supraventricular tachycardia. Ablation targets in these 64 patients included the fast AV nodal pathway (n = 3), the slow AV nodal pathway (n = 14), a posteroseptal accessory pathway (n = 23), and a left lateral accessory pathway (n = 24). A control group of 21 patients undergoing diagnostic study but not ablation underwent identical analysis immediately before and at the conclusion of their procedure. Patients undergoing ablation also had time and frequency domain analysis performed on ambulatory 24-hour Holter tapes recorded before ablation and at 1 day, 1 month, and 6 months after ablation. Compared with preablation values, time domain analysis immediately after ablation revealed a significant increase in mean heart rate and significant reductions in heart rate variability expressed as SD, MSSD, and PNN50 in patients undergoing AV nodal modification or posteroseptal accessory pathway ablation. Frequency domain analysis revealed marked attenuation of high frequency (0.15 to 0.40 Hz) components, indicating parasympathetic denervation. These acute changes were not seen after ablation of left lateral accessory pathways or after diagnostic study without ablation. Time and frequency domain analysis of 24-hour ambulatory Holter monitors performed serially after ablation revealed resolution of abnormalities of heart rate and of heart rate variability 1 to 6 months after ablation, with reappearance of the high frequency parasympathetic component suggestive of reinnervation. CONCLUSIONS: RF ablation in the anterior, mid, and posterior regions of the low interatrial septum may disrupt preganglionic or postganglionic parasympathetic fibers located in these regions that are destined to innervate the sinus node. Such fibers become more scarce along the left AV groove with increasing distance from the posteroseptal space. Parasympathetic denervation may be one mechanism for persistent inappropriate sinus tachycardia after RF ablation.

Adult↗

Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients.

BACKGROUND: Experimental data suggest that aldosterone has harmful effects promoting myocardial fibrosis and disturbing autonomic balance. There has been no evidence of these potential effects in intact man. METHODS AND RESULTS: We report the findings in 31 patients with stable chronic heart failure (CHF) who were treated with spironolactone (50-100 mg/day) or placebo in addition to diuretics and angiotensin converting enzyme (ACE) inhibition. In a controlled randomised double-blind study, we found that spironolactone treatment reduced circulating levels of procollagen type III N-terminal amino peptide, a marker of vascular collagen turnover, and in addition increased time-domain parameters of heart rate variability (n = 24). These latter parameters suggest a parasympathomimetic effect for additional spironolactone. Spironolactone significantly reduced heart rate (prolonged RR interval) particularly during the dawn hours (06.00-09.00 h). In this unbalanced study it was not possible to provide a detailed diurnal assessment of the impact of spironolactone on heart rate variability, but the preliminary data suggest that there may be an interaction with the autonomic nervous system which varies in time. CONCLUSIONS: These are the first human data to show that use of the aldosterone antagonist, spironolactone, can positively improve time-domain heart rate variability and reduce myocardial collagen turnover, as reflected by further reductions in serum procollagen peptide, despite concurrent ACE inhibitor treatment. Residual aldosterone after ACE inhibitor treatment may therefore have a role promoting arrhythmia and cardiac death by two mechanisms. Effects of additional spironolactone on slowing heart rate (and potentially the detrimental effect of aldosterone) were most prominent between 6 a.m. and 10 a.m. when cardiac death is also known to be most prominent.

Aged↗

Management of the heart rate during coronary artery bypass grafting on the beating heart: newly devised methods of decreasing heart rate--a preliminary report-.

BACKGROUND: To develop new methods for achieving bradycardia, we studied the feasibility of producing transient, reversible bradycardia with atrial stimulation and cooling of the sinoatrial node. METHODS: In an animal study, the atrium was stimulated electrically during the refractory period of the atrioventricular node. Alternatively, an area of the sinoatrial node was cooled regionally. The two methods were also performed in combination. In a clinical study, atrial stimulation was applied in seven consecutive patients who underwent coronary artery bypass grafting (CABG). RESULTS: In the animal study, atrial stimulation was effective only when 2 mg/kg of diltiazem was administered. Such atrial stimulation decreased heart rate (beats/minute) from 95.8+/-16.9 to 64.2+/-20.0 (the average reduction from the control value 66.1+/-10.3%). Cooling the sinoatrial node decreased heart rate, and was effective with or without administration of diltiazem. Heart rate was decreased from 156.6 31.7 to 110.7+/-21.7 (average reduction from control value 71.3+/-9.2%) before using diltiazem and from 102.0+/-11.9 to 63.5+/-13.9 (average reduction from control value 62.0+/-10.4%) after administration of diltiazem. By combining the two methods, heart rate was decreased from 102.0+/-12.3 to 44.6+/-9.1 (average reduction from control value 43.5+/-6.3%). In our clinical study, the atrial stimulation method was effective. CONCLUSION: Atrial stimulation or regional cooling of the sinoatrial node slowed the heart rate. By combining the two methods, the heart rate was slowed to 40. Clinically, atrial stimulation was effective in CABG patients.

Aged↗

Heart transplantation in children after mechanical circulatory support: comparison of heart transplantation with ventricular assist devices and elective heart transplantation.

Heart transplantation (HTx) is an ultimate treatment for children with end-stage heart failure or inoperable congenital heart disease. The supply of hearts is inadequate; therefore, different mechanical support systems must be used as bridge to HTx in pediatric patients with postoperative low output. The use of ventricular assist devices (VADs) as bridge to HTx in children is limited because of size differences. The purpose of this study was to evaluate the overall long-term outcome of pediatric circulatory support before pediatric HTx. From 1989 through 2004, 91 pediatric patients underwent isolated HTx. Seven of them required mechanical support before transplantation. We reviewed retrospectively the course of 91 children (mean age 14.7 years) who underwent HTx. Group A consisted of elective HTx patients who were treated as outpatients before HTx, whereas group B was the VAD-HTx bridging group (n=7; mean age 12.31 +/- 2.8 years). Mean duration of VAD support was 108 +/- 98 days (minimum 1 day, maximum 258 days). Overall survival rate after HTx was 80% at 1 year without significant differences between groups. Five of seven patients survived and could be discharged after successful HTx, for a survival rate of 77%. The mean follow-up period was 16.76 +/- 10.6 months. No differences in posttransplantation long-term survival and rejection episodes occurred between patients transplanted with or without VAD. VAD therapy can keep pediatric patients with end-stage heart failure alive until successful HTx, and bridge to HTx is a safe procedure in pediatric patients. After HTx, survival rates of these children are similar to those of patients awaiting elective HTx.

Adolescent↗

A heart-specific CD4+ T-cell line obtained from a chronic chagasic mouse induces carditis in heart-immunized mice and rejection of normal heart transplants in the absence of Trypanosoma cruzi.

To study the role of autoreactive T cells in the pathogenesis of cardiomyopathy in Chagas' disease, we generated a cell line by repeated in vitro antigenic stimulation of purified splenic CD4+ T lymphocytes from a chronically Trypanosoma cruzi-infected mouse. Cells from this line were confirmed to be CD4+ CD8- and proliferated upon stimulation with soluble heart antigens from different animal species, as well as with T. cruzi antigen, in the presence of syngeneic feeder cells. In vitro antigen stimulation of the cell line produced a Th1 cytokine profile, with high levels of IFNgamma and IL-2 and absence of IL-4, IL-5 and IL-10. The cell line also terminated the beating of fetal heart clusters in vitro when cocultured with irradiated syngeneic normal spleen cells. In situ injection of the cell line into well established heart transplants also induced the cessation of heart beating. Finally, adoptive transfer of the cell line to heart-immunized or T. cruzi-infected BALB/c nude mice caused intense heart inflammation.

Animals↗

Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure.

AIMS: Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. METHODS AND RESULTS: We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), beta-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), beta-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with beta-blockers received the target dose. CONCLUSION: ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. beta-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trials.

Adrenergic beta-Antagonists↗

Association of heart rate and heart-rate variability with scores on the emotion profile index in patients with acute coronary heart disease.

We investigated the link between the eight basic emotions named by Plutchik and heart rate, heart-rate variability in the 114 patients, 86 men and 28 women (M = 53.8 yr., SD = 8.0) with acute coronary heart disease during the initial 24-hr. stay in the coronary care unit and again at hospital discharge. Variability in heart rate was significantly positively associated with scores on Trust (the emotional state acceptance) at hospital admission and discharge in the patients with unstable angina and non-Q-wave infarction, on Aggression in the patients with unstable angina at hospital discharge and at hospital admission in the patients with non-Q-wave infarction. There was inverse relation on Timid (the emotional state fear) and Gregarious (joy) at hospital admission and on Distrust (disgust or rejection), Depressed (sadness), and Dyscontrol (impulsiveness) at hospital discharge in the patient with non-Q-wave infarction. There was no significant association between heart-rate variability and the scores on the Emotion Profile Index in the patients with anterior and posterior myocardial infarction. There was no statistically significant association between heart rate and scores on the Emotion Profile Index in the patients with acute coronary disease at hospital admission and discharge. Our results suggest psychological interventions that enhance emotional states represented by the Trust and Aggression scales and minimize those represented by Depressed, Dyscontrol, Timid, and Distrust scales could have a beneficial effect on cardiovascular function in the patients with unstable angina and non-Q-wave infarction in a hospital setting.

Acute Disease↗

Hemodynamic performance in a heterotopically transplanted dog heart: proposal of techniques for working left heart model of heterotopic (abdominal) heart transplantation.

To study hemodynamics together with various aspects of rejection after experimental heart transplantation, we developed a technique to produce a working left heart model of heterotopic (abdominal) heart transplantation. The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. Arterial blood from the recipient abdominal aorta thus perfuses the donor myocardium through the coronary artery, and the donor left ventricle receives venous blood from the recipient inferior vena cava as preload. In this model, the donor left ventricle does not pump out enough venous blood to desaturate the recipient femoral arterial blood but does generate approximately the same pressure as the recipient's heart. This model is reproducible, easy to manage, and can be applied to heterotopic heart transplantation in various experimental animals including rats.

Abdomen↗