[Policy paper nuclear cardiology - update 2018 - Current status of clinical practice]. / Positionspapier Nuklearkardiologie ­ Update 2018.

The joint position paper of the working community "Cardiovascular Nuclear Medicine" of the German Society of Nuclear Medicine (DGN) and the working group "Nuclear Cardiology Diagnostics" of the German Cardiac Society (DKG) updates the former 2009 paper. It is the purpose of this paper to provide an overview about the application fields, the state-of-the-art and the current value of nuclear cardiology imaging. The topics covered are chronic coronary artery disease, including viability imaging, furthermore cardiomyopathies, infective endocarditis, cardiac sarcoidosis and amyloidosis.

The effectiveness of the cardiovascular disease prevention programme 'KardioPro' initiated by a German sickness fund: a time-to-event analysis of routine data.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in the developed world. To reduce this burden of disease, a German sickness fund ('Siemens-Betriebskrankenkasse', SBK) initiated the prevention programme 'KardioPro' including primary (risk factor reduction) and secondary (screening) prevention and guideline-based treatment. The aim of this study was to assess the effectiveness of 'KardioPro' as it is implemented in the real world. METHODS: The study is based on sickness fund routine data. The control group was selected from non-participants via propensity score matching. Study analysis was based on time-to-event analysis via Cox proportional hazards regression with the endpoint 'all-cause mortality, acute myocardial infarction (MI) and ischemic stroke (1)', 'all-cause mortality (2)' and 'non-fatal acute MI and ischemic stroke (3)'. RESULTS: A total of 26,202 insurants were included, 13,101 participants and 13,101 control subjects. 'KardioPro' enrollment was associated with risk reductions of 23.5% (95% confidence interval (CI) 13.0-32.7%) (1), 41.7% (95% CI 30.2-51.2%) (2) and 3.5% (hazard ratio 0.965, 95% CI 0.811-1.148) (3). This corresponds to an absolute risk reduction of 0.29% (1), 0.31% (2) and 0.03% (3) per year. CONCLUSION: The prevention programme initiated by a German statutory sickness fund appears to be effective with regard to all-cause mortality. The non-significant reduction in non-fatal events might result from a shift from fatal to non-fatal events.

Should health insurers target prevention of cardiovascular disease? A cost-effectiveness analysis of an individualised programme in Germany based on routine data.

BACKGROUND: Cardiovascular diseases are the main cause of death worldwide, making their prevention a major health care challenge. In 2006, a German statutory health insurance company presented a novel individualised prevention programme (KardioPro), which focused on coronary heart disease (CHD) screening, risk factor assessment, early detection and secondary prevention. This study evaluates KardioPro in CHD risk subgroups, and analyses the cost-effectiveness of different individualised prevention strategies. METHODS: The CHD risk subgroups were assembled based on routine data from the statutory health insurance company, making use of a quasi-beta regression model for risk prediction. The control group was selected via propensity score matching based on logistic regression and an approximate nearest neighbour approach. The main outcome was cost-effectiveness. Effectiveness was measured as event-free time, and events were defined as myocardial infarction, stroke and death. Incremental cost-effectiveness ratios comparing participants with non-participants were calculated for each subgroup. To assess the uncertainty of results, a bootstrapping approach was applied. RESULTS: The cost-effectiveness of KardioPro in the group at high risk of CHD was € 20,901 per event-free year; in the medium-risk group, € 52,323 per event-free year; in the low-risk group, € 186,074 per event-free year; and in the group with known CHD, € 26,456 per event-free year. KardioPro was associated with a significant health gain but also a significant cost increase. However, statistical significance could not be shown for all subgroups. CONCLUSION: The cost-effectiveness of KardioPro differs substantially according to the group being targeted. Depending on the willingness-to-pay, it may be reasonable to only offer KardioPro to patients at high risk of further cardiovascular events. This high-risk group could be identified from routine statutory health insurance data. However, the long-term consequences of KardioPro still need to be evaluated.

Medida de troponina en circulación mediante un ensayo sensible para la evaluación del riesgo cardiovascular en prevención primaria / Circulating troponin as measured by a sensitive assay for cardiovascular risk assessment in primary prevention / Medição da troponina circulante por um teste sensível para a avaliação de risco cardiovascular na prevenção primária

Background: Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. Methods: We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardio­vascular events (MACE) during 5 years of follow-up. Results: Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. Conclusions: Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

Antecedentes: La medición de troponina cardíaca en circulación mediante nuevos ensayos sensibles ha revelado que incluso mínimas elevaciones se asocian con mayor mortalidad en pacientes con enfermedad arterial coronaria, o incluso en la población general. Sin embargo, menos conocido es el valor incremental o agregado de la medición de la troponina I cardiaca (cTnI) circulante mediante un ensayo sensible para la evaluación del riesgo en prevención primaria. Métodos: Se midieron las concentraciones circulantes de cTnI, de pro- péptido natriurético tipo B N-terminal (NT-proBNP), y de proteína C reactiva de alta sensibilidad (PCRus), en 5388 personas sin enfermedad cardiovascular conocida reclutadas en el estudio DETECT, un estudio prospectivo longitudinal de cohorte de base poblacional. Se determinaron las implicancias pronósticas en la incidencia de eventos adversos cardiovasculares mayores (MACE) durante 5 años de seguimiento. Resultados: La cTnI se detectó en el 19% de los sujetos. El aumento de las concentraciones de cTnI se asoció con factores de riesgo establecidos para la aterosclerosis y demostró una relación gradual con la mortalidad por todas las causas y la incidencia de MACE durante los 5 años de seguimiento. Una sola medición de cTnI mejoró significativamente la predicción del riesgo por encima de los factores de riesgo establecidos, y también agregó información pronóstica cuando se ajustó por la concentración sérica de NT-proBNP y PCRus. Conclusiones: Mínimos incrementos de cTnI se asociaron con mayor mortalidad e incidencia de MACE en una gran cohorte de prevención primaria y, por tanto, la identificación de sujetos con riesgo cardiovascular no siempre son detectados completamente por la evaluación de factores de riesgo tradicionales.

Circulating troponin as measured by a sensitive assay for cardiovascular risk assessment in primary prevention.

BACKGROUND: Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. METHODS: We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. RESULTS: Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. CONCLUSIONS: Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

The prognostic utility of the SYNTAX score on 1-year outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial.

OBJECTIVES: This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents. BACKGROUND: The SXscore can identify patients treated with PCI who are at highest risk of adverse events. METHODS: The SXscore was calculated prospectively in 2,033 of the 2,292 patients enrolled in the RESOLUTE All Comers study (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). Clinical outcomes in terms of a patient-oriented composite endpoint (POCE) of all-cause death, myocardial infarction (MI), and repeat revascularization; the individual components of POCE; target lesion failure (TLF) (a composite of cardiac death, target-vessel MI, and clinically driven target lesion revascularization); and stent thrombosis were subsequently stratified according to SXscore tertiles: SXscore(LOW) ≤ 9 (n = 698), 9 17 (n = 659). RESULTS: At 12-month follow-up, rates of POCE, MI, repeat revascularization, TLF, and the composite of death/MI were all significantly higher in patients in the highest SXscore tercile. Rates of stent thrombosis were all highest in the SXscore(HIGH) tertile (p > 0.05). After multivariate adjustment, the SXscore was identified as an independent predictor of POCE, MI, repeat revascularization, and TLF (p < 0.05 for all). At 12-month follow-up, the SXscore, ACEF score, and Clinical SXscore had C-statistics of 0.57, 0.78, and 0.67, respectively, for mortality and of 0.62, 0.56, 0.63, respectively, for POCE. No significant between-stent differences were observed for TLF or POCE in any of the SXscore tertiles. CONCLUSIONS: The SYNTAX score is able to stratify risk amongst an all-comers population treated with PCI with second-generation drug-eluting stents (DES); however, improvements can be made with the inclusion of clinical variables. (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084).

[Cardiovascular risk assessment by primary-care physicians in Germany and its lack of agreement with the Established Risk Scores (DETECT)]. / Kardiovaskuläre Risikoabschätzung in der Hausarztpraxis (DETECT). Wie gut stimmt die Hausarzteinschätzung mit den etablierten Risikoscores überein?

BACKGROUND: The concordance of several cardiovascular risk scores (PROCAM Score, Framingham Score and ESC Score) and its agreement with the treating physicians' risk assessment is unclear. METHODS: For 8,957 nationally representative primary-care patients without known cardiovascular disease (age 40-65 years), the 10-year risk for experiencing a myocardial infarction or coronary death was determined by using various established risk scores in addition to risk prediction by the treating primary-care physician. RESULTS: In this sample, the mean 10-year coronary morbidity risk was estimated by PROCAM to be 4.9% and 10.1% by the Framingham Score. The mean 10-year cardiovascular mortality risk, estimated by the ESC Score, was 2.9%. According to the risk assessment of the primary-care physicians only 2.7% of the patients were assigned to this group. The number of patients assigned to high, medium and low risk differed substantially. Applying the Framingham Score, 22.6% of all patients were assigned to the high-risk group. Concordance in cardiovascular risk categorization between all three scores was present in only 34.0% of all cases. In 5.9% of the patients the three risk scores yielded completely different risk estimations. Only approximately 8% of the patients assigned to the high-risk group according to the different scores were also recognized as high-risk patients by the primary-care physicians. For approximately 48% of these patients the physician allocated a medium risk and for 41-46% even only a low risk. CONCLUSION: The substantial level of disagreement between the different scores as well as of the scores with the prediction of the treating physicians underlines that risk stratification with the established scores evidently plays no significant role in routine care at this point. Which of the score predictions should be considered to be most sensitive and specific will be examined now prospectively using the 5-year prospective data of the DETECT study.

Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients.

OBJECTIVE: We aimed at investigating the association of age-dependent IGF-I SDS with diabetes, dyslipidemia, hypertension, and heart diseases, in a large patient sample. BACKGROUND: IGF-I has been suggested to be associated with several diseases and a prognostic marker for the development of cardiovascular diseases and risk factors. The findings, though, have been inconsistent possibly due to the methodological factors. METHODS: We studied 6773 consecutive primary care patients, aged 18+ years, in a cross-sectional, epidemiological study in primary care, Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment study. All patients underwent a standardized clinical diagnostic and laboratory assessment. IGF-I levels were measured with an automated chemiluminescence assay system. We calculated the odds ratios (OR) for diseases in quintiles of IGF-I, and additionally analyzed the association of age-dependent IGF-I SDS with these conditions. RESULTS: After multiple adjustments for confounders, we found increased ORs for coronary artery disease in patients with high IGF-I. Women, but not men, with low IGF-I also showed increased ORs for coronary artery disease. Dyslipidemia was positively associated with IGF-I. Type 2 diabetes showed a curvilinear association with IGF-I SDS. CONCLUSIONS: The findings suggest the existence of multiple and complex interactions between IGF-I and several health conditions. The complex nature of disease- and subgroup-specific associations along with the methodological factors can be held responsible for divergent findings in previous studies.

[Prevalence, drug treatment and metabolic control of diabetes mellitus in primary care]. / Prävalenz, medikamentöse Behandlung und Einstellung des Diabetes mellitus in der Hausarztpraxis.

BACKGROUND AND PURPOSE: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. METHODS: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. RESULTS: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value>or=7.0% was recorded in 39.6% of patients. CONCLUSION: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

[Can PCI with drug-eluting stents replace coronary artery bypass surgery? A comparative economic analysis regarding both therapeutic options based on clinical 12-month data reflecting the German social health care insurance system]. / Können Medikamente frei setzende Koronarstents eine Bypassoperation ersetzen? Ein gesundheitsökonomischer Vergleich beider Therapieformen auf der Basis klinischer 12-Monats-Daten.

BACKGROUND AND PURPOSE: It is generally known and accepted that percutaneous coronary intervention (PCI) has undergone a patient-relevant innovation with the introduction of drug-eluting stents (DES): prospective, randomized, controlled studies with a primary clinical endpoint have shown that DES, especially those releasing sirolimus from a polymer (SES) or those releasing paclitaxel from a polymer (PES), significantly and relevantly reduce the restenosis rate and hence the number of needed reinterventions in the target vessel (target vessel revascularization [TVR]) as compared to bare metal stents (BMS). For this improvement of quality of life, cost-effectiveness analyses comparing DES and BMS in the US and German health care systems have been reported. For the comparison of DES and coronary artery bypass graft surgery (CABG), no economic data regarding the German health care system have been published. The goal of the present study is to provide such an economic analysis investigating the question whether DES can reduce costs as compared to CABG within the German health care system. METHODS: Based on the clinical data for PCI with a PES for long and complex lesions (TAXUS VI) and for CABG (ARTS I), the comparison was calculated for the time interval of 1 year. The analysis of the PCI group was derived from a TVR of 11% including a CABG rate of 1%; the CABG group analysis was based on a TVR of 3.8% including a PCI rate of 3.1% and a re-CABG rate of 0.7%. At a stent factor of 2.75, the costs per stent were calculated to be 250 Euro for the BMS and 1,500 Euro for the PES. The total costs for 12 months included the follow-up costs for reinterventions. The results were tested for stability according to a sensitivity analysis. RESULTS: Patients' demographics were well comparable between the PCI and the CABG groups. The primary costs, including the reinterventions, were 7,841 Euro for PCI and 12,415 Euro for CABG. The sensitivity analysis revealed that only at more than eight stents per patient and a need for reintervention of ca. 10% did the cost of PCI with PES reach the level of the cost for CABG. CONCLUSION: Within the German health care system, in patients with a social insurance, PCI of long and complex lesions with PES significantly reduces costs as compared to CABG to the amount of 4,574 Euro per patient. The cost-effectiveness analyses of currently ongoing prospective, randomized trials (SYNTAX und FREEDOM) will provide more insight into the economic comparison of PCI with DES and CABG.

[Off-label use of clopidogrel after coronary stent implantation in Germany: optional or mandatory?]. / "Off-Label"-Verschreibung von Clopidogrel nach Stentimplantation: verzichtbar oder zwingend?

Although the combined use of acetylsalicylic acid (ASA) and clopidogrel represents the standard in the 4-week treatment after coronary stent implantation, a discussion persists in Germany regarding clopidogrel use and the actual measures for cost containment in the healthcare system. Indeed, clopidogrel has not been approved in Germany for use after stent im-plantation. The prescription of clopidogrel in this context is thus considered off-label use. Consequently, patients with social healthcare insurance should pay for clopidogrel out of their own pockets. This regimen, however, bears the inherent risk that patients will not purchase the drug and thus not take it. This overview article describes the risk to patients when social healthcare insurance companies would not pay for clopidogrel after coronary stent implantation. Five international, prospective, randomized and control-led studies in 3,230 patients have shown that "double" antiaggregation, i.e. a combination of ASA and the thienopyridin derivative ticlopidin, compared with ASA alone clearly reduced death, myocardial infarction and the need for another PCI or CABG to a manifold extent. Due to its lower rate of side effects, clopidogrel has replaced ticlopidin since mid-1998. The clinical results of three prospective, randomized studies and seven single-center registries in approximately 14,000 patients have shown that the combination of ASA and clopidogrel results not only in a lower rate of side effects, but also in a significant rate reduction of cardiovascular events of ca. 50% (from 4.0% to 2.1%). Therefore, the combined use of ASA and clopidogrel should be prescribed to avoid (sub)acute stent thrombosis --even if this is not according to the rules of the German healthcare system. The threat of fines to physicians prescribing clopdiogrel at the expense of the social health care insurance is counterproductive and jeopardizes the life of the patients.

Randomized comparison of success and adverse event rates and cost effectiveness of one long versus two short stents for treatment of long coronary narrowings.

Long stents of high flexibility and low profile have become widely available. Treatment of long coronary lesions by 1 long stent may require less interventional efforts and reduce the rate of restenosis due to a lack of overlapping stent segments. This study sought to evaluate the use of 1 long stent compared with 2 short stents for treatment of long coronary lesions. One-hundred twenty-four patients with a coronary lesion 20 to 40 mm in length, in a vessel 2.5 to 4.0 mm in diameter, were randomly assigned to treatment with 1 long stent (GFX II stents or S670 of 24, 30, or 40 mm lengths; n = 62) or 2 stents (GFX II or S670 stents, n = 62) of equal length. Procedural success, interventional costs, as well as long-term clinical and angiographic outcomes were evaluated. Lesion characteristics were similar for the 2 treatment groups. Stent placement was possible as assigned by randomization in 61 of 62 cases (98%) in the 1-long-stent group and 100% of cases in the 2-short-stents group. There was crossover to successful short-stent placement in 1 case. The in-hospital success rate was 97% for the 1-long-stent group and 98% for the 2-short-stents group. Acute angiographic results were similar for both groups after intervention. The angiographic restenosis rate at 6 months was 38.5% in the 1-long-stent group and 37.5% in the 2-short-stents group (p = 0.919). Intervention time was less, and the need for a contrast agent had a tendency to be lower in the long-stent group. Procedural costs were significantly less in the long-stent group. In conclusion, 1 long stent can be used with identical procedural success and adverse event rates as 2 short stents in long, atherosclerotic coronary lesions. The restenosis rate is not reduced by the use of 1 long stent compared with 2 stents. However, long stent placement is highly cost effective.

The IST registry.

Intracoronary brachytherapy has been established in Europe and the US as an evidence-based treatment of in-stent restenoses. The objective of the IST Registry is to register all patients treated in Germany with intracoronary radiation and to observe the clinical outcome for a duration of 5 years. The required set of data for each patient is kept to a minimum to encourage participation. All data are entered online. In the internet, each participating site can, at any time, check their most important parameters and compare them with those of other sites. Presently, the Novoste System is used in 58 catheter labs and the Guidant System in 16, while several sites use both. The requirements regarding radiation safety in intracoronary application of gamma radiation are very strict in Germany, so the Cordis-Gamma System is used in only one German lab. In a first analysis of 332 radiated stenoses, it was observed that late vessel occlusion could occur even after 6-month administration of clopidogrel (in addition to ASA)--without new stents being implanted within the brachytherapy session. Clopidogrel should thus be administered in addition to aspirin for at least a year. Ca. 270 patients per month receive intracoronary radiation in Germany, so the IST Registry will provide important data regarding long-term observation and a foundation for future negotiations with insurance companies potentially bearing the costs. At present, neither the physician's service nor the material costs are reimbursed. The IST Registry can furthermore be used as a comparative database regarding long-term outcome following implantation of antiproliferative-coated stents.