Organization of intensive cardiac care units in Europe: Results of a multinational survey.

BACKGROUND: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe. METHODS: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14). RESULTS: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries. CONCLUSION: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Tissue-muscle perfusion assessed by one day 99mTc-MIBI rest-dipyridamol scintigraphy in non-diabetic and diabetic patients. / Perfusión tejido-músculo evaluada mediante protocolo de un día de gammagrafía reposo-dipiramidol con 99mTc-MIBI en pacientes no diabéticos y diabéticos.

AIM: To determine the perfusion reserve of the lower limbs using the method 99mTc-MIBI (rest-dipyridamole) perfusion scintigraphy (one-day protocol) in the diagnostic evaluation of peripheral artery disease (PAD) in patients with and without diabetes mellitus (DM). MATERIAL AND METHODS: We performed tissue-muscle perfusion scintigraphy (TMPS) of the lower limbs, through one-day rest-dipyridamole protocol with 99mTc-MIBI in 24 patients, divided in two groups according to the presence of diabetes - patients with DM (Dp) 13/24 (54%), 2 males and 9 female patients, age 63±13 years and patients without DM (NDp) 11/24 (46%), 3 males and 10 females, age 61±14 years. RESULTS: In the dynamic phase of the rest study, the time of maximum activity (Tmax), in the early arterial phase, of the calf region was significantly prolonged in Dp compared to NDp, with lower accumulation of the radiotracer in the 1st minute (85%/87% in Dp vs. 89%/90% in NDp, ns). 4/11 of NDp (36.4%) and 7/13 of Dp (53.8%) registered pathological value of the inter-extremity index of the calves in the stress study. Perfusion reserve (PR) of the thighs (LT, RT) and calves (LC, RC) calculated with the formula "(ROI stress-ROI rest)×100%/ROI rest", was significantly lower in Dp: LT: 28±19% vs. 43±24% in NDp, p<0.05; RT: 27±17% vs. 40±25% in NDp, p<0.05; LC: 22±15% vs. 36±15% in NDp, p<0.01; RC: 25±15% vs. 38±14% in NDp, p<0.01. CONCLUSION: This one-day protocol (rest-dipyridamole with 99mTc-MIBI) of perfusion scintigraphy of lower limbs is considered as a useful procedure in PAD assessment, especially the asymptomatic form. TMPS of the lower limbs in our study indicated that perfusion reserve in patients with DM was significantly lower, compared to the patients without diabetes.

Influence of SLCO1B1 polymorphisms on atorvastatin efficacy and safety in Macedonian subjects.

Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin. Hence, the aim of this study was to analyze the association between the SLCO1B1 c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G polymorphisms and lipid-lowering effect and safety of atorvastatin. A hundred and fifty six patients with hyperlipidemia IIa and IIb, all of Macedonian origin, were included in the study receiving atorvastatin 20 - 80 mg/day for 3 months. SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped using the TaqMan allelic discrimination assay. As parameters of atorvastatin response, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A (ApoAI), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), creatine phosphokinase (CPK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, using standard laboratory methods, at baseline and after 3 months of treatment. No statistically significant association between the different SLCO1B1 SNPs and atorvastatin response was observed. However, the carriers of c.521CC manifested a lower decrease in plasma levels of TG, TC, LDL-C and Lp(a), with percentage difference being 16%, 7%, 29% and 149%, respectively, compared to the carriers of c.521TT variant. Lower increase in HDL-C (271%) and ApoAI (293%) and higher increase in CPK (69%) in c.521CC carriers were also observed, confirming the lower OATP1B1 activity in carriers of the variant c.521 C allele. Similar results were obtained when a comparison between the percentage of biochemical parameter change was made between *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers. The lack of a statistically significant association between the SLCO1B1 polymorphism and atorvastatin response can be explained dominantly by the low number of individuals homozygous for the rare c.521C variant allele. Despite this limitation, the study offers valuable information on the influence of the genetic determinant SLCO1B1 on atorvastatin response in the Macedonian population.

Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers.

OATP1B1 is an influx transporter known to mediate the uptake of various endogenous compounds and xenobiotics. Several sequence variations have been discovered in the SLCO1B1 gene encoding OATP1B1. The aim of this study was to investigate the effects of SLCO1B1 polymorphisms on the pharmacokinetics of atorvastatin in healthy volunteers of Macedonian origin. Twenty three participants, genotyped for SLCO1B1 c.388A > G, c.521T > C, c.571T > C, c.597C > T, c.1086C > T, c.1463G > C and c.*439T > G polymorphisms using TaqMan allelic discrimination assay, ingested a single 80 mg dose of atorvastatin. The plasma concentrations of atorvastatin were measured for 48 h using Tandem Liquid Chromatography-Mass Spectrometry, LC-MS-MS, and the peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t1/2), constant rate of elimination (k(el)), mean residence time (MRT, expo), volume of distribution (Vd/kg), clearance (CL/kg), area under curve AUC(0.48h) and AUC(0-∞), were determined. Our data confirmed that the SLCO1B1 gene is highly polymorphic, with a frequency of the c.521T > C single-nucleotide polymorphism (SNP) being the lowest (app. 15%) and of all other SNPs alleles above 40%. Exceptions were c.1463G > C and c.1086C > T SNPs for which variant alleles were not identified. The strongest correlation was observed between the c.521T > C and c.571T > C SNPs pair. The haplotype analysis revealed 10 different haplotypes, with *1J/*1K/*1L being the dominant, with a frequency of app. 40%. The haplotype *15/*16/*17, containing both variant alleles of the functionally most distinguished SNPs, c.388A > G and c.521T > C, occurred with a frequency of 13%. However, *15/*16/*17 homozygotes were not identified in the study group. In this study, no significant differences in the k(el), t1/2, C(max), T(max), AUC(0-48h), AUC(0-∞), MRT expo, Vd and CL between the carriers of different c.388A > G, c.597C > T and c.*439T > G genotypes were observed. Subject with a variant allele C in the c.521T > C SNP, c.521CC genotype, had markedly higher values for C(max) and AUC(0.48h), 140% and 67%, respectively, in comparison with the carriers of the c.521TT genotype. Also, the carriers of the variant allele C at c.571T > C SNP, c.571 CC genotype, had 55% and 43% lower mean C(max) and AUC(0-48h) in comparison with the carrier of c.571TT. These differences lacked statistical significance due to the size of the sample. In addition, no significant differences in the pharmacokinetic parameters of atorvastatin between the *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers were observed. In conclusion, this extensive analysis of the effect of SLCO1B1 polymorphisms on the pharmacokinetic profile of atorvastatin showed that c.521T > C and c.571T > C SNPs may affect the inter-individual response to atorvastatin. Additional studies, with a large sample size, are needed to confirm this finding.

Frequencies of single-nucleotide polymorphisms and haplotypes of the SLCO1B1 gene in selected populations of the western balkans.

As a membrane influx transporter, organic anion-transporting polypeptide 1B1 (OATP1B1) regulates the cellular uptake of a number of endogenous compounds and drugs. The aim of this study was to characterize the diversity of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encoding this transporter in two ethnic groups populating the Western Balkans. The distribution of SCLO1B1 alleles was determined at seven variant sites (c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G) in 266 Macedonians and 94 Albanians using the TaqMan allelic discrimination assay. No significant difference in the frequencies of the single nucleotide polymorphisms (SNPs) was observed between these populations. The frequency of the c.521T>C SNP was the lowest (<13.7 and 12.2%, respectively), while the frequencies of all other SNP alleles were above 40.0%. Variant alleles of c.1463G>C and c.1086 C>T SNPs were not identified in either ethnic group. The haplotype analysis revealed 20 and 21 different haplotypes in the Macedonian and Albanian population, respectively. The most common haplotype in both ethnic groups, *1J/*1K/*1L, had a frequency of 39.0% and 26.6%, respectively. In both populations, the variant alleles of the functionally significant c.521T>C and c.388A>G SNPs existed in one major haplotype (*15/*16/*17), with a frequency of 8.6 and 2.4% in the Macedonian and Albanian subjects, respectively. In conclusion, sequence variations of the SLCO1B1 gene in the studied populations occur at high frequencies, which are similar to that of the Caucasian population. Further studies are needed to evaluate the clinical significance of these SNPs and/ or the major SLCO1B1 haplotypes they form for a large number of substrates and for susceptibility to certain diseases.

Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II Deficiency.

Aim. To raise the awareness of adult-onset carnitite palmitoyltransferase II deficiency (CPT II) by describing clinical, biochemical, and genetic features of the disease occurring in early adulthood. Method. Review of the case characteristics and literature review. Results. We report on a 20-year-old man presenting with dyspnea, fatigue, fever, and myoglobinuria. This was the second episode with such symptoms (the previous one being three years earlier). The symptoms occurred after intense physical work, followed by a viral infection resulting in fever treated with NSAIDs. Massive rhabdomyolysis was diagnosed, resulting in acute renal failure necessitating plasmapheresis and hemodialysis, acute hepatic lesion, and respiratory insufficiency. Additionally, our patient had cardiomyopathy with volume overload. After a detailed workup, CPT II deficiency was suspected. We did a sequencing analysis for exons 1, 3, and 4 of the CPT II gene and found that the patient was homozygote for Ser 113 Leu mutation in exon 3 of the CPT II gene. The patient recovery was complete except for the cardiomiopathy with mildly impaired systolic function. Conclusion. Whenever a patient suffers recurrent episodes of myalgia, followed by myoglobinuria due to rhabdomyolysis, we should always consider the possibility of this rare condition. The definitive diagnose of this condition is achieved by genetic testing.

N-terminal-proB natriuretic peptide in patients with stable coronary artery disease evaluated for ischemia with myocardial perfusion imaging.

BACKGROUND: Natriuretic peptides have emerged in the last years as useful diagnostic and prognostic biomarkers in patients with stable CAD. Myocardial ischemia per se might increase NT-proBNP levels. OBJECTIVES: The aim of the present study was to determine whether NT-proBNP levels in patients with stable CAD and preserved left ventricular function are elevated and second, to compare NT-proBNP in patients with verified ischemia on myocardial perfusion imaging (MPI) to non-ischemic subjects with known CAD. METHODS: 117 patients were prospectively included, divided in two groups: group A (26 patients)--with normal MPI and without known CAD and group B (91 patients)--with abnormal MPI or known CAD. Patients from group B were further divided according to the presence of ischemia on MPI in non-ischemic (29 pts) and ischemic (62 pts) subgroup. RESULTS: Levels of NT-proBNP in group B were significantly higher compared to group A (median 53 vs 21 pg/ ml, p = 0.012). End diastolic and end systolic volumes were higher, and ejection fraction after stress and at rest was lower in group B (63% vs 71%, p = 0.0004 and 69% vs 75%, p = 0.008). No significant difference in NT-pro BNP levels (median 48 vs 62 pg/ml, p = 0.5) and functional parameters between the ischemic and nonischemic subjects was found. CONCLUSION: Our data show that patients with stable coronary artery disease and preserved left ventricular function have elevated levels of NT-proBNP. We could not demonstrate that the presence of myocardial ischemia per se was an additional factor leading to increase of the natriuretic propeptide (Tab. 4, Ref. 12).

Arterial hypertension in patients with coronary artery disease treated with surgical myocardial revascularization.

OBJECTIVES: To evaluate the incidence and prognostic power of arterial hypertension in patients with coronary artery disease treated with surgical myocardial revascularisation, before and after the operation. BACKGROUND: Arterial hypertension is one of the leading modifiable risk factors in CAD patients who underwent CABG surgery with the major impact on clinical outcome in these patients. METHODS: 749 patients with mean age of 55 +/- 8 years, (639 male/119 female) were analyzed for their preoperative: demographic, clinical, left ventricular morphologic and functional and angiographic, perioperative: type of operation, type and number of applied conduits, in-hospital morbidity and mortality, and post-operative: demographic, clinical, left ventricular morphologic and functional and angiographic characteristics. Mean postoperative follow-up period was 5.97 +/- 4.27 years. RESULTS: Hypertension was found in 52.7% of patients before the operation, and it was the most frequent risk factor, without any differences between different age groups, but significantly more often in females (p = 0.0001), diabetics (p = 0.0001), and patients with preserved LV function (p = 0.011). Although significantly correlated with in-hospital morbidity (r = 0.085 and p = 0.023), HTA was not identified as independent predictor. The most predictable was the occurrence of early neurological complications. HTA was also found to be a predictor of long life prognosis in CABG patients, but not as independent prognostic factor. Significant reduction in incidence was found in post-CABG patients (30.1%), which is most likely a result of applied pharmacologic treatment. ACE-inhibitors, Ca-antagonists and B-blockers were applied in 39.44%, 30.1% and 33.6% of patients respectively, with significant positive correlations found for all of them as follows: r = 0.221, p = 0.0001, r = 0.316, p = 000.1 and r = 0.093, p = 0.031. CONCLUSION: Hypertension is the most powerful risk factor in CAD patients who undergo CABG surgery in our country, and a powerful prognostic factor of early and late clinical outcome. There is a trend toward decreasing the incidence of HTA in post-CABG patients, as a result of improved pharmacologic treatment after the operation (Tab. 5, Fig. 1, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

Relationship between myocardial viability and improvement in left ventricular function and heart failure symptoms after coronary artery bypass surgery.

BACKGROUND: The evaluation of myocardial viability is an important preoperative parameter, predictive of improvement in regional and global left ventricular (LV) function after coronary artery bypass surgery (CABG). However, whether the presence of viability is also associated with relief of heart failure symptoms after revascularization is not always certain. The aims of the study were to define the relationship between extent of viable myocardium and improvement in LV function after CABG and to determine whether preoperative viability testing can predict improvement in heart failure symptoms. METHODS: Eighty-five consecutive patients with ischemic cardiomyopathy (mean LVEF 35%) undergoing surgical revascularization were studied with a Tc-99m sestamibi one-day rest/nitrate enhanced myocardial perfusion SPECT imaging (MPI) to assess viability. Regional and global function were measured before and 16 -/+ 6 months after revascularization. We have used the Bull's eye quantitative analysis of MPI scans and 17 segment model of LV function and perfusion evaluation. Heart failure symptoms were graded according to the New York Heart Association (NYHA) criteria, before and 16 -/+ 6 months after revascularization. RESULTS: The number of viable segments per patient was directly related to the improvement in LVEF after revascularization (r 0.79, P < 0.01). Patients with > 4 viable segments representing 24% of the left ventricle yielded the sensitivity of 83% and specificity of 79% respectively for predicting improvement in LVEF. Furthermore, the presence of four or more viable segments predicted improvement in heart failure symptoms after revascularization, with positive and negative predictive values of 79% and 74%, respectively. CONCLUSION: The presence of substantial viability (four or more viable segments, 24% of the left ventricle) on myocardial perfusion gated SPECT imaging in patients with ischemic heart failure before CABG surgery has significant correlation with the improvement in LVEF and heart failure symptoms postoperatively.

Carotid ultrasound, blood lipids and waist determination can predict a future coronary revascularisation in the type 2 diabetic cohort.

The aim of the study was to identify incremental values of carotid ultrasound measurements (carotid plaques and stenosis) on the prediction of future coronary revascularization among type 2 diabetic patients. The second objective was to determine the predictive value of the assessment of blood lipids, BMI, abdominal obesity and the ankle-brachial index (ABI). Three hundred and thirty three (333) patients with type 2 diabetes and manifested coronary artery disease were randomly selected in a cohort prospective study. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of the need for future revascularization: percutaneus coronary interventions (PCI) or coronary bypass surgery (CABG) followed 24 months after the study starting point. The presence of arterial hypertension, hyperlipidemia, physical inactivity, intermittent claudication, the value of systolic pressure, BMI, waist and hip measurement, glycemia and blood lipid fraction (total cholesterol, HDL, LDL, non-HDL, triglycerides) were entered in a model. Ultrasound measurements: carotid IMT, presence of carotid plaques and stenosis, and ABI were also included in the analysis. Based on the univariate and multivariate findings, the presence of internal carotid artery (ICA) stenosis (OR 4,562, 95% CI 1,327-15,687), carotid plaque (OR 1,465, 95% CI 0,829-2,591), and increased waist measurement (OR 1,371, 95% CI 0,757-2,483) were found as significant independent predictors of future PCI. LDL and non HDL cholesterol were found to be factors independently associated with the need for future CABG by univariate analysis, which was not confirmed by multivariate analysis. In conclusion, the current study has provided an identification of predisposing factors for the future need of coronary revascularization among type 2 diabetic patients that permits risk stratification and may facilitate improved patient selection or optimization.

Factors influencing graft potency in patients who underwent CABG for treatment of CAD.

OBJECTIVES: To identify factors that influence graft disease and native coronary arteries progression disease and prognostic implication of this process. BACKGROUND: Unsolved problem in CABG patients is progression of the disease in bypass grafts and native coronary arteries. METHODS: Data from 102 patients with CABG, who underwent re-coronarography, were analyzed: - Pre and post-operative variables: risk factors, clinical status, functional capacity, left ventricular parameters and angiographic status (before and after CABG). Proportional hazard regression model, was used, p<0.05 was considered statistically significant. RESULTS: Cardiac death, myocardial infarction and heart failure were more frequent in patients with graft occlusion, non-stable angina pectoris in non-occlusive graft disease, which together with acute myocardial infarction was more often in patients with native coronary arteries progression disease. PCI was significantly more often performed on native coronary arteries. CONCLUSION: Graft disease and native coronary artery progression disease is a continuous process which can be slowed by aggressive risk factors reduction, medications, and PCI procedures. In contrary, it leads to unfavorable clinical outcome (Tab. 8, Fig. 6, Ref 19).

Prognostic utility of carotid ultrasound and cardiac SPECT imaging in coronary artery bypass patients.

BACKGROUND: The aim of our study was to evaluate the role of myocardial perfusion imaging (MPI) and common carotid artery intima-media thickness (CCA IMT) in the prognosis of patients with coronary artery disease referred for coronary artery bypass surgery (CABG) in a newly made prognostic model. MATERIAL AND METHODS: 63 patients (age 60.36 +/- 8.28 years) with angiographically established coronary artery disease referred for CABG were evaluated for: age, smoking, family disposition, dyslipidaemia, arterial hypertension, obesity, diabetes mellitus, previous myocardial infarction and revascularization. Patients underwent nitrate enhanced Gated SPECT myocardial perfusion imaging, with 17-segment analysis for calculation of perfusion scores and viability index. Common carotid artery IMT was measured by B-mode ultrasound. Patients were followed for cardiovascular events 12 months after CABG. RESULTS: The obtained data reported mean values of left ventricular ejection fraction (LVEF) 46.2 +/- 14.4%, viability index 0.76 +/- 0.55, SRS 17.76 +/- 13.81 and summed nitrate score 12.89 +/- 10.36. Ultrasound detected CCA IMT 0.90 +/- 0.24 mm, with increased value in 67.2% and presence of carotid plaques in 27.1% of pts. We registered 14 events and 8.8% mortality rate. Multiple regression modelling showed bilateral carotid plaque presence as a predictor of total events. Viability index and CCA IMT have been found as independent death predictors. CONCLUSIONS: Myocardial perfusion viability index and CCA IMT are predictors, independently associated with prognosis of patients referred for CABG.

Predictors of in-hospital morbidity and mortality in patients with coronary artery disease treated with coronary artery bypass surgery.

AIM OF THE STUDY: The aim of our study was to identify markers that can predict early morbidity and mortality in patients with coronary artery disease who underwent coronary artery bypass surgery (CABG) for myocardial revascularization. MATERIAL AND METHODS: 749 patients (pts) were enrolled in the study at mean age 55 +/- 8 years, 639 male and 119 female. We analyzed pre-operative demographic, clinical, left ventricular morphologic and functional and angiographic variables, per-operative characteristics, and we registered occurrence of hospital complications including cardiac death during the first 30 days after the operation. RESULTS: Hospital complications were registered in 173 (23.1%) patients, including cardiac death registered in two (3%) patients during the first 30 days after the operation. The most common complications were: pericardial effusion (8.4%), supraventricular arrhythmias (6.3%) and pleural effusion (5.6%), followed by more serious complications like infections, acute renal failure and stroke. Advanced age (>or=65 years), coexisting morbidities and risk factors: cerebrovascular disease (CVD), peripheral vascular disease (PVD), chronic obstructive pulmonary disease (COPD), hypertension (HTA), previous myocardial infarction (MI), heart failure before the operation, extensive coronary artery disease (CAD) (angiographicly identified), low left ventricular ejection fraction (LVEF), and high WMSS index were identified as predictors of in-hospital morbidity. Advanced age, Mod Gensini score (as marker of angiographic severity of CAD) and WMSS index were found to be independent predictors of in-hospital morbidity, while advanced age, heart failure before CABG and in-hospital complications were found to be independent predictors of in-hospital mortality. CONCLUSION: In patients with coronary artery disease who underwent CABG surgery, preoperative variables and operative technique can predict occurrence of in-hospital morbidity, while early complications can strongly predict in-hospital mortality.