Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

[Out-of-hospital resuscitation in Israel 2000].

The aim of the study was to evaluate the impact of pre-hospital cardio-pulmonary resuscitation, performed by mobile intensive cardiac care units of Magen David Adom (MDA) teams in the framework of a national survey conducted in the period February and March 2000. During the survey, MDA performed 539 resuscitations, 485 of which were performed by mobile intensive care units of MDA, and they constitute the study population of the present analysis. The average age of the patients was 70.5 years, and 68% were men. The mean response time of the mobile intensive care units was 10.3 minutes. In 14% of the cases, a bystander initiated basic cardiac life support before the arrival of the MDA team. Upon arrival of the resuscitation team, 242 patients (50%) had asystole, 19% ventricular tachycardia (VT)/ventricular fibrillation (VF), 13% pulseless electrical activity (PEA), and 18% had other severe arrhythmias. One hundred and ninety-nine patients (41%) were transferred alive to the hospital after successful resuscitation. Hospital summaries were obtained for 148 of these patients. The cause of cardiac arrest was cardiac in 64% of the cases and 48% of the patients who reached the hospital had a previous history of heart disease. Fifty-three patients (11%) were discharged alive from the hospital. Patients discharged alive were younger, more promptly resuscitated, 78% had a cardiac cause of death and 38% of them were in ventricular tachycardia/fibrillation when first seen by the resuscitation team. The rate of successful resuscitation to discharge in the sub-group with VT/VF was 21%, and only 4% for patients in asystole, which is in line with other studies. However, the rate of initiation of resuscitation by bystanders is low in Israel. These data may help the medical staff and the health policy providers in Israel.

Opposing effects of endothelin-1 on C-type natriuretic peptide actions in rat cardiomyocytes.

C-type natriuretic peptide (CNP) and Endothelin-1 are paracrine peptides with opposing vascular and mitogenic actions. In cardiac myocytes, CNP reduced contractility and induced accumulation of cyclic guanosine monophosphate (cGMP). Endothelin-1 caused an increase in contractile amplitude, abolished the negative inotropic effect of CNP, reduced the negative inotropic effect of a membrane permeable cGMP, and inhibited cGMP accumulation induced by CNP. We conclude that endothelin-1 abolishes the negative inotropic effect of CNP. This effect may be mediated by inhibition of the negative inotropic actions of cGMP as well as by reduction of cGMP levels.

Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia.

OBJECTIVES: The goal of this study was to investigate the nature of the association between silent ischemia and postoperative myocardial infarction (PMI). BACKGROUND: Silent ischemia predicts cardiac morbidity and mortality in both ambulatory and postoperative patients. Whether silent stress-induced ischemia is merely a marker of extensive coronary artery disease or has a closer association with infarction has not been determined. METHODS: In 185 consecutive patients undergoing vascular surgery, we correlated ischemia duration, as detected on a continuous 12-lead ST-trend monitoring during the period 48 h to 72 h after surgery, with cardiac troponin-I (cTn-I) measured in the first three postoperative days and with postoperative cardiac outcome. Postoperative myocardial infarction was defined as cTn-I >3.1 ng/ml accompanied by either typical symptoms or new ischemic electrocardiogram (ECG) findings. RESULTS: During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained PMI; one of those patients died. All infarctions were non-Q-wave and were detected by a rise in cTn-I during or immediately after prolonged, ST depression-type ischemia. The average duration ofischemia in patients with PMI was 226+/-164 min (range: 29 to 625), compared with 38+/-26 min (p = 0.0000) in 26 patients with ischemia but not infarction. Peak cTn-I strongly correlated with the longest, as well as cumulative, ischemia duration (r = 0.83 and r = 0.78, respectively). Ischemic ECG changes were completely reversible in all but one patient who had persistent new T wave inversion. All ischemic events culminating in PMI were preceded by an increase in heart rate (delta heart rate = 32+/-15 beats/min), and most (67%) of them began at the end of surgery and emergence from anesthesia. CONCLUSIONS: Prolonged, ST depression-type ischemia progresses to MI and is strongly associated with the majority of cardiac complications after vascular surgery.

C-type natriuretic peptide has a negative inotropic effect on cardiac myocytes.

C-type natriuretic peptide (CNP) has vasodilatory and antimitogenic actions, but its role in the control of cardiac function is unclear. We studied the effect of CNP on cultured, beating neonatal rat cardiac myocytes. CNP caused a significant reduction in the amplitude of contraction and a significant accumulation of intracellular cyclic GMP. The effect of a membrane permeable cyclic GMP on cell contraction was similar to that of CNP. CNP caused no change in Ca2+ transients. Blockade of natriuretic peptide receptors abolished the effects of CNP on contraction and accumulation of intracellular cyclic GMP. Blockade of cyclic GMP-dependent protein kinase abolished the effect of CNP on myocyte contraction. We conclude that CNP has a negative inotropic effect on neonatal rat cardiac myocytes. The effect of CNP is mediated via natriuretic peptide receptor(s) causing elevation of intracellular cyclic GMP which possibly activates protein kinase and causes attenuation of myofilament sensitivity to Ca2+.

Cytotoxic T lymphocytes are activated following myocardial infarction and can recognize and kill healthy myocytes in vitro.

The damage of myocardial infarction (MI) is often progressive. A possible mechanism for subsequent myocardial damage and heart failure after MI is immune response against cardiac self-antigens. The purpose of our study was to test the hypothesis that cytotoxic T lymphocytes are activated following acute MI and may have a role in producing further myocardial damage. Rats were allocated into three experimental groups: acute MI, Sham MI and non-operated control. One, two and three weeks after surgery, lymphocytes were obtained from rat spleens and incubated with neonatal cardiac myocytes. Lymphocyte proliferation was assessed by a thymidine incorporation assay and calculated as proliferation index (PI). Myocyte destruction was measured by a crystal-violet staining assay and expressed as percentage of cell destruction. Proliferation index was significantly higher among lymphocytes obtained from MI animals (44. 3+/-5.8 and 44.9+/-5.1, at 2 and 3 weeks after MI, respectively) than sham MI (29.3+/-5.3, 27.1+/-4.7) (P<0.05) or control animals (17.1+/-2.5, 16.2+/-2.8) (P=0.03). Cytotoxic activity of the MI lymphocytes against the cultured cardiomyocytes was significantly higher 2 and 3 weeks after MI, (36.4+/-7.3%, 69.3+/-4.9%) compared to sham MI (17.9+/-3.14%, 36.6+/-5.3%) (P<0.001) and control animals respectively (13.3+/-5.4%, 17.4+/-6.1%) (P<0.001). The cytotoxic activity against healthy cardiomyocytes was myocyte-specific, induced by CD8 lymphocytes and major-histocompatibility complex (MHC) restricted. Cytotoxic T lymphocytes (CD8) are activated following MI and can recognize and kill normal cardiomyocytes in vitro. The newly described pathophysiological insights may provide novel oportunities to prevent death of non-ischemic cardiomyocytes and heart failure following myocardial infarction.

Unusual presentation of familial Mediterranean fever: role of genetic diagnosis.

OBJECTIVE: To describe the role of molecular analysis in the diagnosis of an unusual presentation of familial Mediterranean fever (FMF). CASE REPORT: Two patients presenting with prolonged fever without signs and symptoms of serositis are described. FMF was diagnosed by genetic analysis, which disclosed that both patients were homozygous for the M694V mutation of the Mediterranean fever (MEFV) gene. CONCLUSION: Molecular analysis of FMF should complement the investigation of patients with fever of unknown origin. This test enables a definite diagnosis of the disease and may promote the diagnosis and treatment of patients with an unusual or incomplete clinical picture of FMF.

Changes in cardiac mechanics with heat acclimation: adrenergic signaling and SR-Ca regulatory proteins.

The involvement of adrenergic signaling and sarcoplasmic calcium regulatory proteins in the development of heat acclimation-induced adaptations in cardiac mechanics was studied in heat-acclimated (34 degrees C) rats for 2, 5, and 30 days (AC(2), AC(5), and AC(30), respectively). Control (C) rats were held at 24 +/- 1 degrees C. Systolic pressure (LVP) and velocities of contraction (dP/dt/P) and relaxation (-dP/dt/P) were measured using a Langendorff system. For adrenergic signaling, beta-adrenoreceptor (AR) density and affinity (Scatchard plots) and cardiac inotropic response to norepinephrine (10(-7) mM, +/- 10(-6) mM propranolol) were measured. For the regulatory proteins, steady-state levels of Ca(2+)-ATPase and phospholamban (PLB) mRNAs and the encoded proteins Ca(2+)-ATPase [sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] and PLB were measured using semiquantitative RT-PCR and Western immunoblotting, respectively. Both short (STHA; AC(2) and AC(5))- and long-term heat acclimation (LTHA; AC(30)) enhanced LVP. However, dP/dt. P and -dP/dt. P in STHA hearts resembled that of the controls, whereas on LTHA, both parameters decreased (P < 0.05), implying decreased velocity of contraction and relaxation. beta-AR density remained unchanged with their affinity markedly decreased (P < 0.05). AR responsiveness, however, diminished in AC(2) but was markedly enhanced on LTHA. During STHA, PLB and sarcoplasmic reticulum Ca(2+)-ATPase transcripts were upregulated with no change in the encoded proteins except for SERCA downregulation on AC(5), leading to an increased PLB/SERCA ratio (P < 0.05). This mismatched preacclimation lusitropic state on STHA and increased PLB/SERCA ratio was evident (P < 0.05) due to downregulation of SERCA and upregulation of PLB. Our data fit a biphasic acclimation model in which desensitized adrenergic signaling is dominant during STHA, whereas on LTHA, the contractile machinery is influenced by altered expression of the calcium regulatory proteins leading to both augmented adrenergic inotropic response (via PLB elevation) and decreased velocity of relaxation. The sustained low thyroxin measured on LTHA causally associates with this response.

Acute myocardial infarction--a late complication of intracoronary stent placement.

BACKGROUND: Myocardial infarction (MI) as the first indication of postangioplasty restenosis is extremely rare, and it has been speculated that the fibroproliferative restenotic lesion is less likely to undergo plaque rupture than the lipid-laden native atherosclerotic lesion. HYPOTHESIS: The present study was designed to examine whether intracoronary stent implantation affects this course. METHODS: In all, 994 consecutive patients who underwent angioplasty and intracoronary stent implantation in our hospital were reviewed retrospectively for the occurrence of MI. RESULTS: Eight patients (0.8%), all male and hypertensive, aged 33-83 years, presented with an MI due to stent occlusion more than 30 days following stenting (range: 35-398 days). In two patients, MI occurred 3 and 5 h, respectively, following completion of a maximal high-level exercise test that was negative for ischemia. Angiography revealed complete occlusion or significant stenosis of the stent in all eight patients, with an obvious intimal dissection in either edge of the stent in six patients. Except for gender and hypertension, no correlation was found with other risk factors, vessel involved, initial angiographic results, or with stent design, diameter, or length. CONCLUSIONS: Myocardial infarction as a late complication of successful stent implantation occurred in 0.8% of our patients. This is only the lower bound of the estimated frequency for such an event. We hypothesize that the transition point between the relatively fixed stent and the normal artery is exposed to high deformation stress which makes it vulnerable to rupture and dissection. Strenuous exercise and hypertension may increase the deformation stress and the risk of intimal rupture.

A 42-year-old man with recurrent myocardial infarction and normal appearing coronary arteries.

We report the occurrence of a coronary mural thrombus and recurrent myocardial infarction in a patient with normal-appearing epicardial coronary arteries and small-vessel coronary artery disease. The current case emphasizes the importance of permanent medical treatment with anti-platelet and vasodilators in patients with small-vessel coronary artery disease.

Long-term outcome of patients with very long stents for treatment of diffuse coronary disease.

OBJECTIVES: The study sought to determine the 6-month clinical outcome of patients who underwent implantation of very long coronary stents to treat diffuse disease and/or long dissections and to compare the findings with those reported in the literature for patients who underwent implantation of multiple short coronary stents. BACKGROUND: New designs of flexible stents enable the implantation of long stents rather than multiple short, older design stents. The initial experience is very promising but the long-term outcome has not been described yet. METHODS: Fifty-seven consecutive patients in whom 67 long stents (>/=30 mm) were successfully deployed were included in this study. Six-month clinical and angiographic follow-up was prospectively collected. Patients with recurrent angina underwent coronary angiography without further testing. Patients who remained asymptomatic at the 6-month follow-up visit underwent positron emission tomographic imaging, and those with results suggestive of ischemia underwent coronary angiography. A combined study end point was defined as death, myocardial infarction, and the need for target vessel revascularization. RESULTS: Only 1 patient (2%) reached a study end point at hospital discharge. An additional 20 patients (total 21 patients [37%]) reached an end point by 6 months. The outcome was not influenced by the clinical presentation (stable or unstable angina) or by the indication for stenting (elective or emergency). Predictors for adverse outcome were multiple stents per narrowing (63% vs 29%, P <. 04), and stents smaller than 3.5 mm (49% vs 22%). Narrowing and stent length were not predictive of a study end point in narrowings that were successfully treated by a single long stent. CONCLUSIONS: Elective stenting provides an effective solution for patients with diffuse coronary disease provided that a single long stent (usually <40 mm) can cover the full length of the narrowing. The results are better when vessels larger than 3 mm are treated. Compared with multiple short stents, implantation of a single long stent is probably at least as effective, and the procedure is quicker and cheaper and thus should be the preferred approach.

Heat acclimation induces changes in cardiac mechanical performance: the role of thyroid hormone.

The involvement of reduced thyroxine level in the emergence of heat acclimation-induced negative lusitropic effect was examined. Experiments were carried out on 1) control rat hearts maintained at 24 +/- 1 degreesC (C); 2) rat hearts acclimated at 34 degreesC for 1 mo (AC); 3) AC-euthyroid rat hearts, via administration of thyroxine in the drinking water (AT); and 4) hypothyroid rat hearts, maintained at 24 +/- 1 degreesC, via administration of thiouracil in the drinking water (CP). Systolic pressure and velocities of contraction (dP/dt. P) and relaxation (-dP/dt. P) were measured using the Langendorff perfusion system. The steady-state levels of Ca2+-ATPase and phospholamban mRNAs and the expression of the encoded proteins Ca2+-ATPase (SERCA) and phospholamban (PLB) were measured, using semi-quantitative RT-PCR and Western immunoblotting, respectively. Rat thyroxine levels were measured using RIA. Heat acclimation, which brought about a reduced thyroxine level, led to downregulation of Ca2+-ATPase mRNA expression and translation and upregulation of phospholamban mRNA and PLB. Consequently, the PLB-to-SERCA ratio (PLB/SERCA) of the AC hearts showed a significant increase. These changes, as well as the greater pressure generation and the reduced dP/dt. P and -dP/dt. P observed in AC hearts were blunted in the AT hearts. Our data suggest that sustained heat acclimation-induced low thyroxine level has a decisive effect on the contractile machinery of the AC heart. Elevated PLB/SERCA apparently explains the negative lusitropic effect observed in these hearts.

The Cutting Balloon--a new technology?

The Cutting Balloon consists of a standard balloon dilatation catheter with four microtome-sharp blades that incise the plaque and minimize arterial wall trauma. It was used in 31 patients; nine had calcified arteries, ten had non-compliant lesions, three had in-stent restenosis and nine had aorto-ostial lesions. Seventeen lesions were predilated, 28 were post-dilated and 18 required stent implantation. The procedure was very effective in aorto-ostial lesions, non-compliant lesions that were not responsive to high-pressure balloon dilatation, and was partially successful in calcified arteries. It has a very specific niche in selected lesions.

Acute myocardical infarction due to delirium tremens.

A 36-year-old patient with normal-appearing coronary arteries suffered an acute Q-wave myocardial infarction during acute alcohol withdrawal and delirium tremens. Sympathetic hyperactivity with coronary spasm and increased platelet reactivity are probably the underlying mechanisms.

Highly selective sigma receptor ligands elevate inositol 1,4,5-trisphosphate production in rat cardiac myocytes.

Exposure of cardiac myocytes from adult rat ventricles to the highly selective, high affinity sigma receptor ligands 1S,2 R-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)-cycloh exylamine (BD-737) (0.1-100 nM) and N-[2-(3,4-dichlorophenyl)ethyl]-N,N',N'-trimethylethylenediamine (BD-1047) (0.01-10 nM), caused potentiation of electrically-evoked amplitudes of contraction and Ca2+ transients, while exposure to 100 nM BD-1047 caused attenuation of these amplitudes. In addition, BD-737 (1-100 nM) and BD-1047 (10-100 nM) caused an increase in the incidence of spontaneous twitches. These effects were inhibited when the incubation with BD-737 was done in the presence of the phospholipase C inhibitor, neomycin, or after pre-incubation with thapsigargin or caffeine which deplete the sarcoplasmic reticulum Ca2+ stores. Inositol 1,4,5-trisphosphate (IP3) production in cardiac myocytes was determined by the IP3 binding protein assay. Both substances caused an increase in the intracellular concentration of IP3. BD-737 caused a rapid transient increase to 3.2-fold in 1 min and stabilization at 2.1-fold of control thereafter. BD-1047 caused a gradual increase reaching 4.4-fold after 5 min. The results suggest that the effects of these sigma receptor ligands on contractility and spontaneous contractions are mediated by activation of phospholipase C and elevation of intracellular IP3 level.

Coronary arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia--a case report.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) disease is characterized by cutaneous, mucosal, and visceral vascular anomalies. Two patients were previously described with coronary artery aneurysms (ectasia) associated with this disease. This report describes a patient with Osler-Weber-Rendu disease in whom multiple coronary arteriovenous malformations were identified during coronary angiography. The patient presented with anginal chest pain resulting from severe anemia. Upper gastrointestinal endoscopy revealed multiple angiodysplastic lesions throughout the esophagus and stomach.

New indicator for stent covering area.

A small gap between stent struts is essential to support the vessel wall, prevent elastic recoil, and prevent intimal flaps from prolpasing into the lumen. We defined Gap Index as the ratio of strut width divided by the percent of the vessel wall area covered by the stent metal, and proved mathematically that this index relates inversely to the total length of stent struts (or coil), and directly related to stent cell size. Twenty-four (12 tubular and 12 coil) stents from 17 manufacturers were analyzed. Strut width in the tubular and coil groups was 354.1 +/- 276.0 and 955.9 +/- 553.9 microm, respectively (P < 0.001). The relative metallic surface area (RMS) in the tubular and coil groups for 3 mm stent diameter was 16.0 +/- 4.6 and 10.6 +/- 3.7%, respectively (P < 0.005). Great variations in Gap Index were found amongst different stents, with up to 100-fold. Gap Index in the tubular and coil groups for 3 mm stent diameter was 24.4 +/- 21.7 and 105.8 +/- 97.5 units, respectively (P = 0.001). Thus, coil stents have a smaller relative metallic surface area despite increased strut width. This is the result of reduced total strut length and fewer and larger cells, as represented by a higher Gap Index. This information may be useful for new stents designs.

Pituitary apoplexy as a first manifestation of pituitary adenomas following intensive thrombolytic and antithrombotic therapy.

Apoplexy of a previously asymptomatic pituitary macroadenoma may occur in the setting of intensive thrombolytic, antithrombotic, or anticoagulant therapy for acute myocardial infarction. Classic clinical findings may initially be nonspecific and a high index of suspicion is therefore required for early diagnosis.