Listing criteria for heart transplantation in the Netherlands.

The updated listing criteria for heart transplantation are presented on behalf of the three heart transplant centres in the Netherlands. Given the shortage of donor hearts, selection of those patients who may expect to have the greatest benefit from a scarce societal resource in terms of life expectancy and quality of life is inevitable. The indication for heart transplantation includes end-stage heart disease not remediable by more conservative measures, accompanied by severe physical limitation while on optimal medical therapy, including ICD/CRT­D. Assessment of this condition requires cardiopulmonary stress testing, prognostic stratification and invasive haemodynamic measurements. Timely referral to a tertiary centre is essential for an optimal outcome. Chronic mechanical circulatory support is being used more and more as an alternative to heart transplantation and to bridge the progressively longer waiting time for heart transplantation and, thus, has become an important treatment option for patients with advanced heart failure.

The effect of the titanium butterfly implant on nasal patency and quality of life.

OBJECTIVE: The titanium butterfly implant seems to be a powerful technique to repair nasal valve insufficiency. However, the effect of these implants on nasal patency and quality of life has been controversial due to a lack of evidence. The purpose of this study is to evaluate the objective and subjective effect of the titanium butterfly implant on nasal patency and corresponding quality of life. METHODS: Nasal patency and quality of life of 32 patients undergoing a titanium butterfly implant were evaluated by measuring peak nasal inspiratory flow (PNIF) and completing three validated questionnaires: the NOSE, SNOT-22 and GBI, before surgery, six weeks and six months after surgery. RESULTS: The mean PNIF increased significant after 6 weeks, as well as after 6 months. Both the NOSE and SNOT-22 questionnaire scores showed a significant decrease at both post-operative measurements. The GBI indicated a significant increase at 6 weeks and 6 months. There were no significant differences between both of the post-operative measurements. CONCLUSION: This is the first study indicating that the titanium butterfly implant provides a significant and clinically relevant increase in nasal patency and corresponding quality of life in patients with nasal valve insufficiency.

[Dobutamine therapy at home under the guidance of a nurse practitioner, either as a bridge to cardiac transplantation or as destination therapy in severe heart failure]. / Dobutaminetherapie thuis als brug naar harttransplantatie of als einddoeltherapie bij ernstig hartfalen begeleid door de 'nurse practitioner'.

OBJECTIVE: To evaluate the results of intravenous dobutamine therapy at home for ambulatory patients with severe heart failure. DESIGN: Retrospective. METHOD: Data were retrieved for the 40 patients that had been treated with intravenous dobutamine at home during the period from 1 January 1994 until mid-November 2006 at the Thorax Centre of Groningen University Medical Centre, The Netherlands. The patients were guided by a nurse practitioner. RESULTS: The study group comprised 31 men and 9 women. The 22 patients on the waiting list for a heart transplant had an average age of 49 years. For the other 18 patients, on average 63 years old, it was destination therapy. The mean administered dosage ofdobutamine was 4 microg/kg/ min (range: 2-10). Pre-transplantation and destination therapy were given for an average of 3.5 and 1.5 months, respectively. A successful transplantation was performed in 14 (64%) of the 22 waiting-list candidates; 2 patients were still on the waiting list and 6 died while on the waiting list. Intravenous access complications and ICD shocks each occurred in 6 (15%) patients. The quality of life was reasonable to fair in the waiting-list patients and moderate to reasonable in those given destination therapy. The costs for medication and hire of the infusion pump were Euro 450 per month. CONCLUSION: Dobutamine infusion therapy at home under the guidance of a nurse practitioner, either as a bridge to cardiac transplantation or as destination therapy in patients with severe heart failure, appeared safe, feasible and not expensive.

Long-term outcome after heart transplantation performed in the University Medical Centre Groningen.

BACKGROUND: Ten years ago, there was a difference of opinion about the suitability of ventilated patients with end-stage cardiac failure for heart transplantation (HTX). Although guidelines at that time qualified mechanical ventilation as a contraindication, we thought those patients could be candidates for HTX. In the same period a number of other patients received a donor heart in our centre. In this article we describe the clinical course and survival after these procedures. METHODS: We performed a retrospective study using our post HTX database. All patients undergoing transplants in our hospital were selected. Patients underwent echocardiography, scintigraphy (MUGA), ergo-spirometry (VO2 peak), blood tests and completed a quality of life questionnaire (SF-36). All tests were completed in the 1st quarter of 2006. RESULTS: Eight patients were identified; three were mechanically ventilated at the time of HTX. All eight patients were treated according to the standard protocol. Repeated surveillance cardiac biopsies were taken. One patient died 3.5 years after HTX due to an acute myocardial infarction. Seven patients, including the three patients on a ventilator at the time of the HTX, are alive, resulting in a survival rate of 88%. The current median survival time is 126 months (range 55 to 184 months). All patients are in good cardiac condition. The SF-36 domains of social functioning and mental health show high scores, the average score of general health and vitality is moderate. CONCLUSION: Survival of our eight transplanted patients after a median period of ten years was 88%, which is at least comparable with data from larger series. This finding suggests that HTX can be performed effectively and safely in a low volume centre. The finding that all three patients on a ventilator prior to HTX are alive is remarkable. It appears that mechanical ventilation is not always an absolute contraindication for HTX.

Volume conduction effects in EEG and MEG.

Volume conductor models that are commonly used to describe the EEG and MEG neglect holes in the skull, lesions, the ventricles, and anisotropic conductivity of the skull. To determine the influence of these features, simulations were carried out using the finite element method. The simulations showed that a hole in the skull will have a large effect on the EEG, and as one of the consequences localisation errors up to 15 mm may occur. The effect on the MEG is negligible. The presence of a lesion may cause the shape and magnitude of the EEG and MEG to change. Hence, a lesion has to be taken into account, if the active neurones are close to it. Moreover, a localisation procedure may fail if the lesion is not included in the volume conductor model. Inclusion of the ventricles in the volume conductor model is necessary only if sources are in their vicinity or if their sizes are unusually large. Anisotropic conductivity of the skull has a smearing effect on the EEG but does not influence the MEG.

Clinical and neurohumoral differences between spirapril and captopril in mild to moderate chronic congestive heart failure.

BACKGROUND: This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. METHODS AND RESULTS: The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo2) was 17.4 mL/min/kg (range, 14.2-19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13-40%). Exercise duration in the captopril group showed a significant increase after 12 weeks (P < .05) of treatment compared with the spirapril group. Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients. Serum ACE activity was significantly different between the two treatment groups during treatment (P < .0001) and showed only a significant decrease in the spirapril group. There was no difference in improvement of quality of life between the two treatment groups. CONCLUSIONS: This study showed that the effects of the ACE inhibitors spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.

Angiographic left ventricular wall motion score to predict arrhythmia recurrence in patients with sustained ventricular tachycardia or fibrillation.

METHODS: Sixty-nine patients with sustained ventricular tachyarrhythmias were followed up to evaluate the predictive value of functional capacity (i.e., New York Heart Association class and peak oxygen consumption) and resting left ventricular function (i.e. radionuclide left ventricular ejection fraction, angiographic left ventricular wall motion score and echocardiographic dimensions) with respect to arrhythmia recurrence. RESULTS: During a mean follow-up of 19 months 18 patients (26%) had an arrhythmia recurrence. Parameters of functional capacity and echocardiographic dimensions were not related to arrhythmia recurrence. Left ventricular ejection fraction and wall motion score were worse in patients with a recurrence compared with the arrhythmia-free patients: 30 +/- 16% versus 40 +/- 19% (mean +/- SD, P = 0.035) and 25 +/- 7 versus 20 +/- 7 (P = 0.01), respectively. Multivariately the most powerful parameter was left ventricular wall motion score (odds ratio 1.12, 95% Cl 1.02-1.23). CONCLUSIONS: Arrhythmia recurrence in ventricular tachyarrhythmia patients relates to resting left ventricular function and not to functional capacity. Since angiographic left ventricular wall motion score is prognostically more important than ejection fraction this parameter should be considered for risk stratification in these patients.

Acute hemodynamic and long-term clinical effects of isradipine in patients with coronary artery disease and chronic heart failure. A double-blind, placebo-controlled study.

To assess the acute hemodynamic and long-term clinical effects of isradipine, a calcium antagonist of the dihydropyridine class, we performed a double-blind, placebo-controlled parallel study in 19 patients with coronary artery disease (CAD) and stable chronic heart failure (CHF). Their mean age was 56 +/- 5 years, and left ventricular ejection fraction (LVEF) was 0.18 +/- 0.05. Patients were treated with diuretics and digoxin only. All were clinically stable and in sinus rhythm. The acute hemodynamic study showed that (intravenous) isradipine increased cardiac index (+36%) and stroke volume index (+30%) (both P < 0.001), while systemic vascular resistance (-33%) and mean arterial pressure (-10%) decreased (both P < 0.005). Filling pressures and heart rate were not affected. Of the 19 patients, 17 completed the 12 week study; 2 patients on placebo (1 death, 1 side-effects) but no patient on isradipine (5 mg 3 times daily) dropped out. After 12 weeks, peak oxygen consumption (VO2), LVEF, echocardiographic indices, and other clinical parameters were unaffected by treatment. Repeat invasive hemodynamic measurements showed that the initial improvement by isradipine was not present anymore. In conclusion, despite a beneficial acute hemodynamic effect, isradipine has no favorable clinical influence during prolonged treatment in patients with mild to moderate CHF.

Computation of neuromagnetic fields using finite-element method and Biot-Savart law.

The finite-element method in combination with the Biot-Savart law is described to compute the magnetic field distribution generated by a dipolar source within a homogeneous volume conductor of an arbitrary shape. In order to calculate the three independent components of the magnetic field outside the volume conductor by means of the Biot-Savart law, the distribution of the current throughout the medium is required. A finite-element mesh is constructed using four-node tetrahedral elements. The potential in each node is computed numerically by the finite-element method using the proper continuity conditions across the boundaries. The gradient of the potential denotes the current density within an element. The components of the magnetic induction are calculated by numerical integration, applying the current density within the tetrahedrons. Simulations are carried out to assess the numerical accuracy for a homogeneous spherical volume conductor. Errors of 3% can be obtained with a locally refined spherical mesh containing about 1000 nodes, for dipoles at any depth and any orientation. A homogeneous realistically shaped model with the shape of the inside of the skull is obtained from magnetic resonance images.

Effects of spirapril and captopril on regional blood flow in chronic congestive heart failure: a comparison between a short- and a long-acting angiotensin-converting enzyme inhibitor.

Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the spirapril group. Calf BF showed a slight but not significant increase in both spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with spirapril. Although filtration fraction (FF) tended to decrease in the spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.

Exploratory study of the effects of single doses of isomazole on hemodynamics and heart rate variability parameters in chronic heart failure.

Ventricular arrhythmias and disturbed autonomic control, as reflected by abnormal heart rate variability (HRV), are related to hemodynamic impairment in chronic heart failure (CHF). We investigated the effects of orally (p.o.) administered isomazole, a new phosphodiesterase (PDE) inhibitor with calcium-sensitizing properties, on hemodynamics, ventricular arrhythmias, and HRV and examined a possible interaction between these parameters. Hemodynamic measurements and ambulatory ECG monitoring were performed in 12 patients with stable CHF class III-IV after single doses of isomazole 5-30 mg. Pulmonary wedge pressure decreased after 5, 10, 20, and 30 mg, but cardiac output, (CO) increased only after the higher doses [20 mg, + 20% (p = 0.031)] of isomazole. HR did not change. Mean arterial and pulmonary artery pressure, (MAP, PAP) decreased significantly in the 10- and 20-mg groups [10 mg, -6% (p = 0.035) and -14% (p < 0.001) respectively; 20 mg, -13% (p = 0.047) and -31% (p = 0.006), respectively]. Isomazole did not exert a significant effect on ventricular arrhythmias in the subsequent 24 h after acute dosing. Analysis of HRV showed that rMSSD and pNN50 (parameters of vagal tone) tended to increase after isomazole administration. Normalized high-frequency power during the day increased from 17.4 to 22.3 nu (p < 0.05), whereas low frequency tended to decrease from 52.7 to 48.2 nu (p = 0.06). Acute isomazole administration improves hemodynamics but has no effect on ventricular arrhythmias. The HRV variability data suggest development of an increase in vagal control of HR, parallel to the acute hemodynamic improvement after isomazole. Withdrawal of vagal control of HR in CHF may be a reversible process.

Functional capacity before and after cardioversion of atrial fibrillation: a controlled study.

OBJECTIVE: To evaluate the effect of cardioversion on peak oxygen consumption (peak VO2) in patients with long-standing atrial fibrillation, to assess the importance of underlying heart disease with respect to the response to exercise, and to relate functional capacity to long-term arrhythmia outcome. DESIGN: Prospective controlled clinical trial. SETTING: Tertiary referral centre. PATIENTS: 63 consecutive patients with chronic atrial fibrillation accepted for treatment with electrical cardioversion. Before cardioversion all patients were treated with digoxin, verapamil, or a combination of both to attain a resting heart rate < or = 100 beats per minute. INTERVENTIONS: Electrical cardioversion. MAIN OUTCOME MEASURES: Peak VO2 measured before and 1 month after electrical cardioversion to compare patients who were in sinus rhythm and those in atrial fibrillation at these times. Maintenance of sinus rhythm for a mean follow up of 19 (7) months. RESULTS: Mean (1SD) peak VO2 in patients in sinus rhythm after 1 month (n = 37) increased from 21.4 (5.8) to 23.7 (6.4) ml/min/kg (+11%, P < 0.05), whereas in patients with a recurrence of atrial fibrillation 1 month after cardioversion (n = 26) peak VO2 was unchanged. In patients who were in sinus rhythm both those with and without underlying heart disease improved, and improvement was not related to functional capacity or left ventricular function before cardioversion. Baseline peak VO2 was not a predictive factor for long-term arrhythmia outcome. CONCLUSION: Restoration of sinus rhythm improved peak VO2 in patients with atrial fibrillation, irrespective of the presence of underlying heart disease. Peak VO2 was not a predictive factor for long-term arrhythmia outcome after cardioversion of atrial fibrillation. These findings suggest that cardioversion is the best method of improving functional capacity in patients with atrial fibrillation, whether or not they have underlying heart disease and whatever their functional state.

Chronotropic response to exercise in patients with atrial fibrillation: relation to functional state.

OBJECTIVE: To determine the relation between functional capacity and heart rate response to exercise in patients with atrial fibrillation. SUBJECTS: 73 consecutive patients with chronic atrial fibrillation. MAIN OUTCOME MEASURES: Relation between functional capacity, measured as peak oxygen consumption (peak VO2; ml/min/kg), and heart rate at all stages of exercise in univariate and multivariate analyses. RESULTS: Peak VO2 showed no correlation with resting heart rate, but it showed a negative correlation with heart rate during the first stage of exercise (r = -0.94, p < 0.01). Indeed, heart rate during the early stages of exercise (stages 1-5) was higher in patients with a peak VO2 less than or equal to 20 ml/mm/kg than in those with a peak VO2 greater than 20 ml/min/kg (heart rate 140 v 125 beats/min, p < 0.05). At maximal exercise, however, peak VO2 was positively correlated with heart rate (r = 2.15, p < 0.0001). CONCLUSION: In patients with atrial fibrillation and impaired functional capacity heart rate at low levels of exercise is augmented but maximal heart rate attenuated compared with patients with preserved functional capacity. Excessive heart rate responses to minor exercise may have deleterious effects on left ventricular function and thereby further limit functional capacity.

Mode of death in patients with congestive heart failure: comparison between possible candidates for heart transplantation and patients with less advanced disease.

To study whether the relative incidence of sudden death versus progressive congestive heart failure is related to the severity of congestive heart failure as assessed by determination of peak oxygen consumption, we followed 90 ambulatory patients with moderate to severe congestive heart failure for 24.1 +/- 13.1 months. All patients had a left ventricular ejection fraction of 40% or less (mean, 22.6% +/- 9.2%) and a peak oxygen consumption of 20 ml/min/kg or less (mean, 14.7 +/- 3.5 ml/min/kg). Patients with severe congestive heart failure who might be eligible for heart transplantation (group I: n = 37; peak oxygen consumption < or = 14 ml/min/kg, mean, 11.0 +/- 1.8 ml/min/kg; mean left ventricular ejection fraction, 22.3% +/- 9.3%) were compared with those considered too well for heart transplantation (group II: n = 53; peak oxygen consumption > 14 < or = 20 ml/min/kg, mean, 17.1 +/- 1.6 ml/min/kg; mean left ventricular ejection fraction, 22.9% +/- 9.1%). During follow-up, 15 patients (41%) in group I died; 11 patients (21%) in group II died. In group I, seven of the 15 deaths (47%) were sudden; in group II, nine of the 11 deaths (82%) occurred suddenly. Patients who died suddenly had a significantly higher peak oxygen consumption (14.0 +/- 3.5 ml/min/kg) than those who died of progressive congestive heart failure (11.0 +/- 3.1 ml/min/kg; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in vasomotor control between human gastroepiploic and left internal mammary artery.

BACKGROUND: Internal mammary artery grafts have a greater long-term patency rate than do saphenous vein grafts. This has in part been attributed to the difference in endothelial function of arterial and venous vessels. The use of the gastroepiploic artery in coronary artery bypass grafting has become popular recently because of its similarity to internal mammary artery. In this study, we compared the endothelial responses of gastroepiploic and left internal mammary arteries to vasoactive substances. METHODS AND RESULTS: Gastroepiploic and left internal mammary arteries were obtained during surgery from patients undergoing elective coronary artery bypass surgery. Vascular rings of both graft types were studied in organ bath experiments. Relaxation responses to metacholine and sodium nitrite were similar in rings of both arteries. In contrast, bradykinin induced potent relaxations in rings of the gastroepiploic artery but not in rings of the left internal mammary artery. Furthermore, there was a inverse correlation of maximal metacholine-induced relaxations with increasing age. CONCLUSIONS: The resemblance of relaxations induced by metacholine and sodium nitrite in both gastroepiploic and left internal mammary arteries suggests a similar activation and behavior of the L-arginine pathway in both arteries. The difference in bradykinin-induced relaxations may reflect a prostaglandin metabolism in the gastroepiploic artery different from that in the left internal mammary artery. Furthermore, maximal metacholine-induced relaxation in rings of the left internal mammary artery shows an age dependency that was not observed in rings of the gastroepiploic artery.

Comparison of treatment with lisinopril versus enalapril for congestive heart failure.

The effect of lisinopril 5-20 mg once daily or enalapril 5-20 mg once daily on exercise capacity, ventricular ectopic activity, and signs and symptoms of heart failure have been studied in 278 patients with mild-to-moderate (New York Heart Association [NYHA] classes II and III) heart failure in a randomized, double-blind, parallel-group study of 12 weeks' duration. Exercise duration was significantly increased by both angiotensin-converting enzyme (ACE) inhibitors after 6 and 12 weeks of treatment compared with their respective baseline values. There was a trend toward a greater increase in exercise duration on lisinopril after 12 weeks, although this did not reach statistical significance (p = 0.0748). There were no significant treatment differences with respect to the effect of the 2 drugs on ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Both drugs were equally effective in improving NYHA grading and symptoms. Neither treatment had any significant effect on mean heart rate or mean blood pressures. Both treatments were equally well tolerated. The most commonly reported adverse events on both drugs were cough, dizziness, fall in blood pressure, vertigo, and myocardial infarction. The results of this study indicate that lisinopril 5-20 mg once daily is at least as effective and well tolerated as enalapril 5-20 mg once daily.

Comparison between New York Heart Association classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

To compare the value of the New York Heart Association (NYHA) classification and measurement of peak oxygen consumption (VO2) in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure (CHF), 94 patients with clinically stable NYHA class II and III CHF were prospectively studied. In all patients, left ventricular ejection fraction was less than or equal to 40% (mean 22 +/- 9); 49 patients were in NYHA class II, and 45 were in NYHA class III. Mean peak VO2 was 17 +/- 5 ml/min/kg. During a follow-up period of 23 +/- 11 months, 21 patients died. The 1-, 2- and 3-year cumulative survival rates for the 94 patients were 88, 79 and 69%, respectively. Functional status, as assessed both by peak VO2 and NYHA classification, and left ventricular ejection fraction were significantly worse in the group of nonsurvivors. The most powerful independent predictor of mortality was peak VO2. Although mean peak VO2 was significantly higher in NYHA class II than in NYHA class III (20 +/- 4 vs 13 +/- 3 ml/min/kg, p less than 0.0001), categorization into subgroups on the basis of the attained peak VO2 revealed a marked discrepancy with the NYHA classification. Nevertheless, the survival curves of patients subdivided at a peak VO2 of 16 ml/min/kg showed a strong resemblance with survival curves of both NYHA classes.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute hemodynamic, hormonal, and pharmacokinetic properties of oral spirapril in patients with moderate to severe heart failure.

The acute hemodynamic, hormonal, and pharmacokinetic responses to the oral angiotensin-converting enzyme (ACE) inhibitor spirapril were studied in 15 patients with moderate to severe congestive heart failure in a baseline controlled dose-ranging study. Doses of 0.3, 1.0, 1.5, 3.125, and 6.25 mg were investigated for 24 h in three groups of five patients each. All doses demonstrated a significant reduction in serum ACE, even after 24 h. Significant reductions in mean arterial pressure, systemic vascular resistance, and pulmonary capillary wedge pressure were observed with doses greater than 1.0 mg spirapril. Maximal significant hemodynamic effects occurred approximately 4-6 h after drug administration. The plasma concentrations of spirapril and its metabolite spiraprilate were dose-dependent. After administration of spirapril, the quick rise to the peak level of spiraprilate suggests rapid metabolism of spirapril into spiraprilate and a slow elimination of this metabolite. No severe hypotension or other serious side effects occurred in the patients studied. The results indicate that spirapril may be expected to be an effective drug in the treatment of congestive heart failure. From our findings we conclude that 1.5 mg spirapril is an optimal starting dose in patients with moderate to severe congestive heart failure.