A dataset of criteria on the use of thermal insulation solutions in building facades located in Norway, Portugal and Italy.

The building sector is responsible for a significant percentage of the energy consumption in Europe. The level of thermal insulation of the building envelope leads to decrease energy consumption, thus contributing towards a sustainable and efficient built environment. As a result, the choice of the most suitable thermal insulation solution to be applied both in new construction and in retrofitting of building facades is fundamental for a satisfactory thermal performance of the building. Nevertheless, the thermal insulation solution should not be chosen considering only the thermal performance, but rather based on a set of performance parameters (i.e., water resistance, fire performance, impact on the environment and human health, among others) and climate-related requirements. This data article includes a dataset on criteria adopted in three European countries (namely Norway, Portugal, and Italy) considering a PESTE analysis (i.e., criteria related to Political, Economic, Social, Technological, and Environmental questions). The main objective was to evaluate the knowledge and perception of people living and/or working in these countries about the use and the performance of thermal insulation solutions in building facades. To this aim a questionnaire was developed within the scope of the EEA Granted EFFICACY research project (November 2022 - February 2023), whose overall objective is to create a database that serves as a reference for the choice of thermal insulation solutions to be applied in building facades for thermal and energy performances optimization. This database contributes to systemize criteria and can be extended by other researchers or professionals in the area, as well as in other countries.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Effectiveness and safety of dabigatran versus acenocoumarol in 'real-world' patients with atrial fibrillation.

AIMS: Randomized trials showed non-inferior or superior results of the non-vitamin-K-antagonist oral anticoagulants (NOACs) compared with warfarin. The aim of this study was to assess the effectiveness and safety of dabigatran (direct thrombin inhibitor) vs. acenocoumarol (vitamin K antagonist) in patients with atrial fibrillation (AF) in daily clinical practice. METHODS AND RESULTS: In this observational study, we evaluated all consecutive patients who started anticoagulation because of AF in our outpatient clinic from 2010 to 2013. Data were collected from electronic patient charts. Primary outcomes were stroke or systemic embolism and major bleeding. Propensity score matching was applied to address the non-randomized design. In total, 920 consecutive AF patients were enrolled (442 dabigatran, 478 acenocoumarol), of which 2 × 383 were available for analysis after propensity score matching. Mean follow-up duration was 1.5 ± 0.56 year. The mean calculated stroke risk according to the CHA2DS2-VASc score was 3.5%/year in dabigatran vs. 3.7%/year acenocoumarol-treated patients. The actual incidence rate of stroke or systemic embolism was 0.8%/year [95% confidence interval (CI): 0.2-2.1] vs. 1.0%/year (95% CI: 0.4-2.1), respectively. Multivariable analysis confirmed this lower but non-significant risk in dabigatran vs. acenocoumarol after adjustment for the CHA2DS2-VASc score [hazard ratio (HR)dabigatran = 0.72, 95% CI: 0.20-2.63, P = 0.61]. According to the HAS-BLED score, the mean calculated bleeding risk was 1.7%/year in both groups. Actual incidence rate of major bleeding was 2.1%/year (95% CI: 1.0-3.8) in the dabigatran vs. 4.3%/year (95% CI: 2.9-6.2) in acenocoumarol. This over 50% reduction remained significant after adjustment for the HAS-BLED score (HRdabigatran = 0.45, 95% CI: 0.22-0.93, P = 0.031). CONCLUSION: In 'real-world' patients with AF, dabigatran appears to be as effective, but significantly safer than acenocoumarol.

Validation and clinical use of a novel diagnostic device for screening of atrial fibrillation.

AIMS: Patients with asymptomatic and undiagnosed atrial fibrillation (AF) are at increased risk of heart failure and ischaemic stroke. In this study, we validated a new diagnostic device, the MyDiagnostick, for detection of AF by general practitioners and patients. It records and stores a Lead I electrocardiogram (ECG) which is automatically analysed for the presence of AF. METHODS AND RESULTS: In total, 192 patients (age 69.4 ± 12.6 years) were asked to hold the MyDiagnostick for 1 min, immediately before a routine 12-lead ECG was recorded. Atrial fibrillation detection and ECGs stored by the MyDiagnostick were compared with the cardiac rhythm on the 12-lead ECG. In a second part of the study, the MyDiagnostick was used to screen for AF during influenza vaccination in the general practitioner's office. Atrial fibrillation was present in 53 out of the 192 patients (27.6%). All AF patients were correctly detected by the MyDiagnostick (sensitivity 100%; 95% confidence interval 93-100%). MyDiagnostick AF classification in 6 out of 139 patients in sinus rhythm was considered false positive (specificity 95.9%; 95% confidence interval 91.3-98.1%). During 4 h of influenza vaccination in 676 patients (age 74 ± 7.1 years), the MyDiagnostick correctly diagnosed AF in all 55 patients (prevalence 8.1%). In 11 patients (1.6%), AF was not diagnosed before, all with a CHA2DS2VASc score of >1. CONCLUSION: The high AF detection performance of the MyDiagnostick, combined with the ease of use of the device, enables large screening programmes for detection of undiagnosed AF.

Volume control in treatment-resistant congestive heart failure: role for peritoneal dialysis.

Chronic congestive heart failure (HF) has a rising prevalence and increasing impact on health care systems. Current treatment consists of diuretics, renin-angiotensin-aldosterone system blockers, and restriction of salt and fluids. This strategy is often hampered by a drop in effective circulating volume and hence renal perfusion and function, triggering harmful counter regulatory mechanisms. Slow ultrafiltration by peritoneal dialysis (PD) might be an effective treatment strategy to relieve fluid overload without compromising cardiac output and thereby renal function. In this review, we discuss the (patho)physiological mechanisms of the cardiorenal interaction and the current literature on PD strategies in congestive HF.

Automatic seizure detection in rats using Laplacian EEG and verification with human seizure signals.

Automated detection of seizures is still a challenging problem. This study presents an approach to detect seizure segments in Laplacian electroencephalography (tEEG) recorded from rats using the tripolar concentric ring electrode (TCRE) configuration. Three features, namely, median absolute deviation, approximate entropy, and maximum singular value were calculated and used as inputs into two different classifiers: support vector machines and adaptive boosting. The relative performance of the extracted features on TCRE tEEG was examined. Results are obtained with an overall accuracy between 84.81 and 96.51%. In addition to using TCRE tEEG data, the seizure detection algorithm was also applied to the recorded EEG signals from Andrzejak et al. database to show the efficiency of the proposed method for seizure detection.

Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.

AIMS: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown. METHODS AND RESULTS: Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction < or =0.40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12 +/- 4%, as compared to those without atropine (P < 0.05). Left ventricular end diastolic pressure increased less in the atropine group (+40 +/- 8% vs +78 +/- 6%;P < 0.05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23 +/ -4% more in the atropine group (P < 0.05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13 +/- 6% (atropine) vs -19 +/- 4% (controls), ST-segment depression 1. 3 +/- 0.6 (atropine) vs 1.8 +/- 0.2 mm (control), both P < 0.05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced. CONCLUSION: In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia.

Wavelet transform-based QRS complex detector.

In this paper, we describe a QRS complex detector based on the dyadic wavelet transform (Dy WT) which is robust to time-varying QRS complex morphology and to noise. We design a spline wavelet that is suitable for QRS detection. The scales of this wavelet are chosen based on the spectral characteristics of the electrocardiogram (ECG) signal. We illustrate the performance of the Dy WT-based QRS detector by considering problematic ECG signals from the American Heart Association (AHA) data base. Seventy hours of data was considered. We also compare the performance of Dy WT-based QRS detector with detectors based on Okada, Hamilton-Tompkins, and multiplication of the backward difference algorithms. From the comparison, results we observed that although no one algorithm exhibited superior performance in all situations, the Dy WT-based detector compared well with the standard techniques. For multiform premature ventricular contractions, bigeminy, and couplets tapes, the Dy WT-based detector exhibited excellent performance.

Acute anti-ischemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function.

Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.

Renal hemodynamic effects in patients with moderate to severe heart failure during chronic treatment with trandolapril.

Treatment of patients with severe heart failure by ACE inhibition is often limited by worsening of renal function. To evaluate whether trandolapril, a potent lipophilic ACE inhibitor, affects renal function in severe heart failure, we studied 12 patients with severe heart failure treated with only diuretics and digoxin. Patients received increasing oral dosages of trandolapril (0, 1, and 2 mg) on 3 consecutive days (A). Patients were then discharged on 2 mg trandolapril bid and re-evaluated 8 weeks later (B). Mean arterial and pulmonary wedge pressures decreased by maximal 14% and 43%, and stroke volume and work indexes increased by 24% and 20% at A and similarly at B (11, 45, and 25 ns and 33%, respectively). In contrast, heart rate, systemic resistance, pulmonary artery pressure, and cardiac index decreased by 6%, 23%, 29%, and 17%, respectively, at only A. Renal blood flow improved by approximately 40% both at A and B. In contrast, the glomerular filtration rate decreased by 25% at only B, whereas serum creatinine, creatinine clearance, and urine osmolality were unaffected during the study. Norepinephrine, angiotensin II, and aldosterone levels decreased by approximately 30%, 60%, and 65%, respectively, at both A and B. Renin levels increased by 136% at A and remained elevated at B. Thus, whereas the initial systemic vasodilating and inotropic effects did not persist, long-term trandolapril results in sustained neurohormonal modulation, reduced preload, and improved organ perfusion, indicated by a persistent increase in renal blood flow and preservation of renal function in severe heart failure.

[Self-assessment of the medical expert and his cooperation with the practicing medical team]. / Das Selbstverständnis des ärztlichen Gutachters und seine Zusammenarbeit mit der niedergelassenen Arzteschaft.

This article reflects the roles of medical experts concerned with assessment and evaluating and their co-operation with treating doctors. Mutual role assignments are described as well as role allocation and role acceptance. Procedures and contents of co-operation between expertising and treating doctors are listed. Co-operation is understood as an integrative task.

Effects of epanolol, a selective beta1-blocker with intrinsic sympathomimetic activity, in patients with ischemic left ventricular dysfunction.

Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.

Early administration of ramipril in acute myocardial infarction: neurohormonal and hemodynamic effects and tolerability.

Although several large studies indicate a beneficial effect of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction, the optimal timing of therapy in terms of safety and the effects on neurohormones during myocardial infarction are less well known. In order to investigate the effect of ramipril, administered within 24 h after myocardial infarction, on hemodynamics and neurohormones and its safety, 20 patients with a myocardial infarction were studied. Nine patients had an anterior, 10 an inferior, and 1 a non-Q-wave infarction. Fourteen patients received thrombolytic therapy, whereas 6 did not. The initial dose of ramipril was 1.25 mg, but was gradually increased to 5 mg during the next 4 days. Side effects did not occur. The mean arterial pressure decreased 8 h after the first dose from 84 +/- 2 mm Hg (control) to 77 +/- 2 mm Hg (p < 0.05) and remained decreased thereafter. This was accompanied by a reduction in systemic resistance of 8% after 8 h and of 12% on day 2. Heart rate, cardiac and stroke indexes, and pulmonary artery and wedge pressures did not change. The ACE activity decreased within 1 h of ramipril administration with a maximum of 71% at 4 h after the second dose and remained at this level throughout the study. Angiotensin II decreased by 34% (day 2) and by 41% (day 5). The renin activity gradually increased from 33 +/- 7.5 to 75.4 +/- 11.5 microM/ml on day 5, whereas epinephrine was reduced from day 2 onwards, with a maximal reduction of 71% on day 5. Arginine vasopressin was significantly reduced 5 h after ramipril administration until the end of the study, with a maximum of 77% on day 3. Moreover, a late but significant decrease in norepinephrine occurred on day 5. Thus, oral ramipril results in early ACE inhibition, followed by progressive attenuation of the neuroendocrine activation and a reduction in afterload during the acute phase of myocardial infarction. It is well tolerated, also in combination with nitroglycerin and thrombolytic therapy.

Acute myocardial ischaemia induces cardiac carnitine release in man.

In animal studies, prolonged periods of ischaemia decrease the cardiac carnitine content. However, whether in humans the heart loses carnitine during short-term ischaemia, and whether this is related to ischaemia-induced cardiac dysfunction, is as yet unknown. Carnitine kinetics were investigated in 28 normotensive patients with significant left coronary artery disease, during and after incremental atrial pacing. To evaluate carnitine kinetics from the ischaemic area, patients were grouped as those with (n = 22) or without (n = 6) myocardial lactate production. Atrial pacing resulted in a comparable maximal heart rate and ST depression in both groups. Carnitine kinetics did not change in those without lactate production. In contrast, coronary venous free carnitine levels increased significantly by 9% during pacing in those with lactate production. Cardiac free carnitine balance changed from uptake (255 +/- 107 pmol.min-1, mean +/- SEM) to release, (-150 +/- 66 pmol.min-1) at 30 min after pacing in the group with lactate production. Arterial and coronary venous differences in free carnitine were significantly correlated with myocardial lactate extraction immediately after pacing. The change in coronary venous free carnitine was significantly correlated with the change in left ventricular ejection fraction at 10 min after pacing. Thus, in patients with coronary artery disease, short-term mild myocardial ischaemia results in significant cardiac free carnitine loss.

Contrasting preload-dependent hemodynamic and neurohumoral effects of isomazole, a partial phosphodiesterase inhibitor and calcium sensitizer.

BACKGROUND: Currently evaluated positive inotropic agents that act predominantly through phosphodiesterase III-inhibiting properties, have been disappointing in the treatment of heart failure. Lack of efficacy as a result of diminished cellular cyclic adenosine monophosphate and vasodilating tolerance and side effects are prevalent. In contrast, calcium sensitization is preserved in heart failure and agents that combine phosphodiesterase-inhibiting and calcium-sensitizing properties may be more efficacious. Isomazole is such a novel agent with combined properties. This study investigated the acute hemodynamic and neurohormonal effects of intravenous isomazole (3 micrograms/kg/min for 30 minutes). METHODS AND RESULTS: The effects of preexisting preload were evaluated in 18 patients with heart failure, New York Heart Association class II/III, and elevated (> 15 mmHg, n = 11, group I) and normal; (n = 7, group II) pulmonary wedge pressure at baseline. In the overall group, isomazole increased myocardial contractility and relaxation and decreased systemic resistance by 20%. Left and right filling pressures fell by 35-45%, accompanied by a 69% reduction in cardiac atrial natriuretic peptide release. In contrast, levels of arterial norepinephrine and renin both increased by 27%. Cardiac output increased in group I (23%), but fell in group II (18%), accompanied by a 51% increase in arterial norepinephrine. Cardiac atrial natriuretic peptide decreased in group I, but not in group II. CONCLUSIONS: Isomazole induced positive inotropic and lusitropic effects and arterial vasodilation in all patients. Cardiac pump function improved only in group I, accompanied by a reduction in sympathetic activity and renin-angiotensin and aldosterone levels and a more pronounced decrease in cardiac atrial natriuretic peptide release. In contrast, in patients with normal to low preload, the further reduction in preload led to a deterioration of pump function and increased sympathetic tone.

Acute hemodynamic effects and preload-dependent cardiovascular profile of the partial phosphodiesterase inhibitor nanterinone in patients with mild to moderate heart failure.

Nanterinone (UK-61,260) is a novel positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety. As its acute hemodynamic effects in humans are unknown, an oral dose of 2 mg nanterinone was studied in 14 patients with heart failure (NYHA class II-III) on chronic diuretic and angiotensin-converting enzyme (ACE) inhibitor treatment. Before the study, patients were on a 2 g salt-balanced diet, and they received their last medication 16 hours before each study day. Hemodynamic measurements were carried out before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours after administration of the study drug. All patients received placebo and nanterinone on 2 consecutive days. Following nanterinone, systemic vascular resistance decreased immediately from 1699 +/- 82 (mean +/- SEM) at baseline to 1368 +/- 80 at 1 hour. Changes persisted for 12 hours. Concomitantly, there was an immediate and significant fall in pulmonary wedge pressure to 38% of baseline at 1.5 hours, together with a 20% reduction in pulmonary artery pressure. Heart rate remained unchanged and arterial pressures showed only a short, significant decrease. Cardiac index rose significantly from 2.28 +/- 0.15 at baseline to a highest value of 2.65 +/- 0.14 1/min/m2 at 1 hour. Changes persisted for 3 hours. Placebo had no effect on these variables. As, in view of its potential venodilating properties, hemodynamic improvement by nanterinone may depend on pre-existing left ventricular filling pressure, patients were subsequently grouped according to baseline pulmonary wedge pressure of > 12 mmHg (H-PCWP) and < or = 12 mmHg (L-PCWP). Cardiac index improved by 26% in H-PCWP and by 17% in L-PCWP (NS). In contrast, PCWP fell more markedly in H-PWCP than in L-PCWP (40% and 23%, respectively, p < 0.05). Thus, oral nanterinone results in a significant acute hemodynamic improvement and is well tolerated. Although changes in left ventricular filling pressure are more pronounced in patients with elevated pre-existing PCWP, cardiac pump function improves equally in patients with normal or low left ventricular filling pressure at baseline.

Anti-ischaemic efficacy of L-propionylcarnitine--a promising novel metabolic approach to ischaemia?

L-propionylcarnitine, a naturally occurring derivative of L-carnitine, essential for mitochondrial fatty acid transport and high-energy phosphate exchange, acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac dysfunction following intravenous administration. This randomized, crossover study was designed to compare the long-term anti-ischaemic effects of oral L-propionylcarnitine with diltiazem in patients with stable, exercise-induced angina. After a 2-week washout phase of anti-anginal medication and a 2-week single-blind placebo period, 46 patients were included in the study, 23 of whom received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the other treatment after a 1-week washout period. Three patients on L-propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in comparable exercise duration (582 +/- 35 s and 588 +/- 33 s, mean +/- SEM), time to 0.1 mV ST depression (436 +/- 38 s and 465 +/- 36 s), and increase in time to 0.1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and diltiazem, respectively. Diltiazem decreased the rate-pressure product at rest and exercise, L-propionylcarnitine did not. Both compounds significantly reduced ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem), P < 0.05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to onset of angina by 22%. In contrast, no significant changes occurred with L-propionylcarnitine. During the study, anginal attacks were reduced by 70% and 57%, and nitroglycerin consumption decreased by 57% and 70%, L-propionylcarnitine and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose) diltiazem result in anti-ischaemic effects and decrease anginal attacks in daily life. Although the effect of diltiazem on exercise-induced ischaemia appears more pronounced than that of L-propionylcarnitine, this novel metabolic approach to ischaemia warrants further development.

Additional antiischemic effects of long-term L-propionylcarnitine in anginal patients treated with conventional antianginal therapy.

Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function. To evaluate possible antiischemic effects of L-propionylcarnitine was compared with placebo in a randomized, double-blind, parallel design, in addition to preexisting therapy. Patients with > or = 2 anginal attacks per week and objective signs of ischemia with angina during bicycle exercise testing were included. After an initial 2-week, single-blind placebo phase, 37 patients received 500 mg L-propionylcarnitine tid, and 37 patients received placebo for 6 weeks. Both groups were comparable at baseline. Three patients discontinued the study while on placebo (two because of noncompliance, one because of palpitations) and one while on L-propionylcarnitine (noncompliance). Although heart rate, blood pressure at rest, and maximal exercise were not affected, L-propionylcarnitine increased the time to 0.1 mV ST-segment depression [44 +/- 3 vs. 8 +/- 2 seconds (mean +/- SEM) in the placebo group; p = 0.05], and exercise duration improved by 5% compared with placebo. Anginal attacks and the consumption of nitroglycerin were not affected in either group. Thus, following a 6 week treatment period, L-propionylcarnitine induced additional, albeit marginal, antiischemic effects in anginal patients who were still symptomatic despite maximal conventional antianginal therapy. It is questionable whether in these patients this form of metabolic treatment will achieve great benefit, although in some improvement can be expected.

Anti-ischaemic effects of converting enzyme inhibitors: underlying mechanisms and future prospects.

ACE inhibitors have the potential to affect myocardial ischaemia in patients with asymptomatic ventricular dysfunction and ischaemic cardiomyopathy after long-term treatment. However, anti-ischaemic effects are virtually absent in stable effort angina during short-term therapy, which suggests different mechanisms of action in different patient subtypes. Long-term treatment in left ventricular dysfunction may lead to a reduction in myocardial oxygen demand and ischaemia as a result of ventricular remodelling, possibly supported by structural coronary vascular effects, i.e., an improved endothelial function and vasodilator capacity. An alternative mechanism by which ACE inhibitors may affect ischaemia, is through modulation of ischaemia-induced neurohormonal activation and subsequent systemic vasoconstriction. Depending on the severity of ischaemia, pronounced catecholamine activation and stimulation of the circulating renin-angiotensin system occur, accompanied by systemic vasoconstriction and an increase in afterload. These changes are marked in patients with left ventricular dysfunction. Moreover, a change from net catecholamine release to uptake in the ischaemic area is observed. Although the clinical significance of the latter observation is still unclear, sympathetic activation may lead to coronary vasoconstriction in stenotic areas where normal endothelium-dependent coronary vasodilatation has become impaired. In the resting patient, enalaprilat and perindoprilat significantly reduce myocardial ischaemia, not by a direct effect on the oxygen supply-demand ratio, but through modulation of neurohormonal activation, in particular of sympathetic activation during ischaemia, and, subsequently, by preventing systemic vasoconstriction. These effects are pronounced in left ventricular dysfunction, at least where perindoprilat is concerned. The possibility that ACE inhibitors improve endothelial function in concert with their modulating effects on ischaemia-induced neurohormonal activation and hence influence the occurrence of myocardial ischemia during long-term treatment needs further evaluation.