NURSING ARTICLE

Main topic

Herz 2019 · 44:210–217 https://doi.org/10.1007/s00059-019-4798-3 Published online: 21 March 2019 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

P. Valensi1 · C. Meune2

1 Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Bondy, France

2 Department of Cardiology, Avicenne Hospital, Inserm UMR-942, Paris Nord University, Bobigny, France

Congestive heart failure caused by silent ischemia and silent myocardial infarction Diagnostic challenge in type 2 diabetes

Besides atherosclerotic complications, heart failure (HF) has emerged in the past 20 years as a serious cardiovas- cular complication in patients with type 2 diabetes mellitus (T2D). Several epidemiologic studies such as the Fram- ingham [1], the Reykjavik [2], and the Strong Heart [3] studies have shown the increased risk of HF in these patients. In recent cardiovascular outcome tri- als (CVOTs) designed in T2D patients with a history of cardiovascular disease (CVD) or with several associated risk factors, the incidence of hospitalization for HF (hHF) was comparable to the incidence of acute myocardial infarction [4].

In diabetic patients, the control of risk factorsisabletomitigatetheexcessriskof atheroscleroticcomplicationsbuttherisk of HF remains high [5]. Thus, HF has be- come a major challenge in CVD preven- tion, highlighting the necessary careful consideration of this outcome in CVOTs. This should ultimately guide the choice of antihyperglycemic agents in order to promote new drugs that can reduce the risk of HF and to avoid those that may in- duce/be harmful in HF, which is particu- larly important in patients with coronary artery disease (CAD).

Coronary artery disease is the lead- ing cause of HF in T2D patients. Heart failure occurs mostly in patients with known CAD [6]. However, CAD is of- ten silent and may be detected at a stage of silent myocardial infarction or using stress tests of ischemia. Silent myocardi-

al ischemia, particularly when associated with coronary stenoses, is predictive of an increased risk of cardiovascular out- comes. Some data suggest that HF may occuras a complication of previously un- detected silent CAD.

The aim of this article is (a) to sum- marize the data on the risk of congestive HF in T2D patients with silent myocar- dial infarction or silent ischemia, and (b) to report on how to estimate and reduce this risk.

Heart failure in patients with CAD and diabetes

Coronary artery disease accounts for half of the cases of HF, regardless of whether the patients have diabetes or not [7]. In theOregonregistry, CADwastwicemore frequent (41 vs. 18%) and the prevalence ofhypertensionwashigherindiabeticpa- tients who developed HF compared with those who did not [8]. Biochemical and microcirculatory factors may aggravate myocardial changes in ischemic HF and further impair the prognosis of patients with ischemic HF.

Renal disease may also increase the risk of HF. In a recent meta-analysis of CVOTs testing SGLT2 inhibitors that in- cluded 60% of patients with established CVD, mostly with CAD, the risk of hHF in the placebo arms was around four times greater in the patients with an esti- mated glomerular filtration rate (eGFR) of <60ml/min per m2 than in those with eGFR ≥90ml/min per m2 [9].

Subclinical cardiac autonomic neu- ropathy(CAN)consistingmainlyinade- pression of vagal activity and sympa- thetic overdrive is frequent in patients with T2D. In a small series of patients with either prediabetes or diabetes, CAN was associated with diastolic dysfunction [10]. In a population of 293 T2D pa- tients, we showed that patients with both CAN and silent myocardial ischemia had a lower left ventricular ejection fraction (LVEF)andthatCANwasassociatedwith a reduced diastolic time that could alter myocardial perfusion (Valensi et al., un- published data). Thus, CAN might con- tribute to the excess HF risk in patients with CAD.

In patients with HF, recent large reg- istries have demonstrated a significant association between diabetes and ad- verse outcomes including CVD death, all-cause death and hHF, independent of HF etiology, ischemic or not, or phenotype [11–15].

Silent CAD and risk of heart failure in diabetic patients

High prevalence of silent CAD in diabetes

Up to 50% of myocardial infarctions are undetected at the time of occurrence and are discovered later during routine care or when cardiovascular symptoms have emerged [16] or are revealed by car- diac imaging. The prevalence of silent myocardialinfarctionindiabeticpatients

210 Herz 3 · 2019

as detected by resting electrocardiogra- phy (ECG) is about 4% and markedly higherwhenusingcardiacmagneticreso- nanceimagingormyocardialsingle-pho- tonemissioncomputedtomography[17]. Theincidenceofsilentmyocardialinfarc- tion as detected by ECG is higher in dia- beticpatientswithahistoryofmyocardial infarction[17]. IntheFIELDstudy, silent myocardial infarction detected on rou- tine standard ECG accounted for more than one third of the first cases of myo- cardial infarction and two thirds of cases after a first myocardial infarction [18]. In the RECORD study, a retrospective analysis of ECGs showed that one third of prevalent and one quarter of inci- dent myocardial infarctions were unrec- ognized [19]. In a population of 9243 participants from the ARIC (Atheroscle- rosis RiskinCommunities)studyinclud- ing 8% with diabetes, about one half of all myocardial infarctions were clinically silent (detected on ECG reading), and the proportion of diabetic patients was twice greater among the patients with silent or clinical myocardial infarction than among those without myocardial infarction [20]. However, a limitation to these studies is related tothe ECG criteria usedforthedetectionofsilentmyocardial infarction. The sensitivity and specificity of Q waves have been questioned in stud- ies that attempted to correlate Q waves with myocardial damage evaluated by positron emission tomography, scintig- raphy, and magnetic resonance imaging [21, 22]. The reason may be that Q waves can resolve with time, and several non- ST segment elevation myocardial infarc- tions (NSTEMI) do not have Q waves on ECGs [23].

In asymptomatic diabetic patients with other risk factors, the prevalence of silent myocardial ischemia detected by stress tests is variable in the literature, mostly reported to be around 20–30% [24–27]. This discrepancy is explained partly by differences in patient selection and choice of stress tests. The prevalence of silent myocardial ischemia progres- sively decreases in the diabetic popula- tion probably in line with an improved risk factor control [28]. Regarding the screening methods, the combination of exercise ECG with an imaging technique

(myocardial perfusion imaging or stress echocardiography) provides incremental diagnostic value [29]. Silent myocardial ischemia is associated with significant coronary stenoses on angiography in 40–90% of cases, meaning that ischemia may also result from functional disorders including endothelial dysfunction [30], abnormal microcirculation, and reduced coronary reserve [31, 32].

Coronary artery disease may also be detected using computed tomogra- phy (CT), which allows for noninvasive estimation of the coronary calcifica- tion (using the coronary artery calcium [CAC] score) and detection of coronary atherosclerotic plaques and stenosis (CT coronary angiography). A CAC score of >400 Agatston units (AU) that may affect around 20% of asymptomatic diabetic patients [33] was shown to increase the risk of all-cause mortality more than four times [34]. The CAC score is synergistic with myocardial perfusion scintigra- phy for the prediction of cardiovascular events [35]. Screening patients for silent myocardial ischemia should be limited to very high risk patients such as those with evidence of peripheral artery dis- ease, proteinuria, or renal failure. A high CAC score may also be used as a first-line test to identify very high risk patients who may justify being screened for silent myocardial ischemia [36].

Prognosis of silent CAD in diabetic patients and risk of HF

The risk of cardiovascular events in di- abetic patients was reported to be as high after silent and clinical myocar- dialinfarction(aroundfourfoldincrease) compared to diabetic patients without myocardial infarction [18]. Only a few studies, including the Rotterdam, Heart Framingham, and ARIC studies, exam- ined the risk of incident HF in silent myocardial infarction as a separate out- come. For instance, in the ARIC study, after a median follow-up of 13 years the incidence rate of hHF was higher in both thegroupofparticipantswithclinicaland with silent myocardial infarction than in those without myocardial infarction (30.4, 16.2, and 7.8 per 1000 person- years, respectively; p< 0.001), with the

same trend noted for patients with or without diabetes [20]. As recently sum- marized[37], allthesestudiesreachedthe conclusion that silent myocardial infarc- tion is associated with an increased risk of HF, independent of usual risk factors, which suggests that the changes in struc- ture and function of cardiomyocytes in the ischemic heart and other unidenti- fied mechanisms need to be considered and targeted to prevent the occurrence of HF.

Silent myocardial ischemia is a strong predictorofcardiovascularoutcomes[38, 39], and adds to the prediction of an event above and beyond routine assess- ment of risk prediction [40]. The prog- nosis is worse when the extent of myo- cardial perfusion defects on scintigraphy is large [39] and when silent myocar- dial ischemia is associated with signifi- cant coronary stenoses on angiography [38], a high CAC score [35], or cardiac autonomic neuropathy [41]. However, no prospective study has ever reported a higher occurrence of HF in patients withdetectedsilentmyocardialischemia, which might be due to underpowered studies, to the lack of attention to this outcome, or to a too-short follow-up. In patientswithHF,however, previouslyun- recognized CAD often seems to be in- volved. In a series of 136 patients under 75 years hospitalized for HF in the UK, invasive coronary angiography was un- dertaken in 99 cases; CAD was consid- ered to be the etiology of HF in 71 of the patients while in 18 of these 71 patients the ischemic etiology was not recognized prior to angiography [42]. In a Japanese study, 155 consecutive patients hospital- ized with HF, of whom 65 patients had diabetes, underwent invasive coronary angiography. In the study cohort, 59 patients had coronary stenoses, diabetes was more prevalent in the group with stenoses (63% vs. 29%), and diabetes was the only independent predictor of steno- sis [43]. Thisstronglysuggeststhatprevi- ous silent CAD was often present, which supports performing coronary imaging in diabetic patients with HF and with- out clear etiology so as to confirm the presence of coronary stenosis.

Herz 3 · 2019 211

Abstract · Zusammenfassung

Herz 2019 · 44:210–217 https://doi.org/10.1007/s00059-019-4798-3 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

P. Valensi · C. Meune

Congestive heart failure caused by silent ischemia and silent myocardial infarction. Diagnostic challenge in type 2 diabetes

Abstract In asymptomaticpatients with type 2 diabetes (T2D), the prevalence of silent myocardial infarction on routine electrocardiograms is about 4% while for silent myocardial ischemia it is 20–30%. Some studies showed that silent myocardial infarction is associatedwith an increased risk of incident heart failure (HF), whereas no prospective study has ever reported such a risk in patients with silent myocardial ischemia. In patients with HF, how- ever, previously unrecognized coronary artery disease (CAD) often seems to be involved. Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels represent first-line diagnostic tools for patients with suspected HF and might also serve as biomarkers

for silent CAD. Echocardiography provides a detailed report of cardiac alterations that includes changes suggestive of ischemia, heart failure, and left ventricular dysfunction in addition to strong prognostic indices. Diabetic patients with silent myocardial infarction or silent myocardial ischemia should be screened for asymptomaticchanges in left ventricular function or structure. In patients with silent CAD, all risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. In patients with congestive HF and no obvious cause of HF, invasive coronary angiography (or noninvasive computed tomography angiography) should be performed to detect

CAD, since the finding of CAD may involve revascularization and requires additional treatments including antiplatelet agents and statins. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction.

Keywords Diabetes mellitus, adult-onset · Coronary artery disease · Antihyperglycemic agents · Risk assessment · Prognosis

Kongestive Herzinsuffizienz durch stumme Ischämie und stummen Herzinfarkt. Diagnostische Herausforderung bei Typ-2-Diabetes

Zusammenfassung Bei asymptomatischen Patienten mit Typ- 2-Diabetes (T2D) liegt die Prävalenz des stummen Herzinfarkts im Routineelektro- kardiogramm etwa bei 4%, die Prävalenz der stummen Myokardischämie dagegen bei 20–30%. In einigen Studien zeigte sich, dass ein stummer Herzinfarkt mit einem erhöhten Risiko für eine neu auftretende Herzinsuffizienz (HF) einhergeht, jedoch ist ein solches Risiko bei Patienten mit stummer Myokardischämie bisher nicht in einer prospektiven Studie dokumentiert worden. Bei Patienten mit HF scheint häufig eine zuvor unbekannte koronare Herzkrankheit (KHK) mitbeteiligt zu sein. Für Patienten mit Verdacht auf HF stellen die Werte für BNP („brain natriuretic peptide“) und NT-proBNP („N-terminal pro-BNP“) die diagnostischen Parameter der ersten Wahl dar, die sich auch

als Biomarker für eine stumme KHK eignen könnten. Die Echokardiographie ermöglicht zusätzlich zu soliden prognostischen Anhaltspunkten einen detaillierten Einblick in kardiale Veränderungen einschließlich Hinweisen auf Ischämie, Herzinsuffizienz und linksventrikuläre Dysfunktion. Patienten mit Diabetes und stummem Herzinfarkt oder stummer Myokardischämie sollten auf asymptomatische Veränderungen der linksventrikulären Funktion oder Struktur hin gescreent werden. Bei Patienten mit stummer KHK müssen alle Risikofaktoren besser einge- stellt und die Auswahl antihyperglykämischer Substanzen angepasst werden. Bei Patienten mit kongestiver HF und ohne offensichtliche Ursache der HF sollte eine invasive Koro- narangiographie (oder eine nichtinvasive Computertomographie-Angiographie)zur

Diagnose der KHK durchgeführt werden. Denn die Feststellung einer KHK könnte auch eine Revaskularisierung beinhalten und erfordert eine zusätzliche Behandlung mit Thrombozytenaggregationshemmern und Statinen. Zukünftige Untersuchungen sind erforderlich, um die Wirtschaftlichkeit des Screenings auf stumme Myokardischämie als Teil der HF-Risikobeurteilung zu ermitteln und präventive Behandlungen zur Senkung des HF-Risikos bei Patienten mit stummem Herzinfarkt zu identifizieren.

Schlüsselwörter Diabetes mellitus mit Beginn im Erwach- senenalter · Koronare Herzkrankheit · Antihyperglykämische Substanzen · Risikobeurteilung· Prognose

Association between silent CAD and echocardiographic changes

In a large population of asymptomatic T2Dpatients, wescreenedforsilentmyo- cardial ischemia by stress scintigraphy andperformedinvasivecoronaryangiog- raphy in those who had silent myocar- dial ischemia. All patients underwent echocardiography at rest, and we showed that in patients with silent myocardial is-

chemia, the positive predictive value of LV hypertrophy associated with another echocardiographic abnormality (includ- ing LV dilatation, systolic dysfunction, and hypokinesia) for CAD was 63% [44]. Inaddition, among the normotensive pa- tients the prevalence of LV hypertrophy and hypokinesia was 30% and 13%, re- spectively, in those with CAD as com- pared with 24% and 5% in those without CAD [45]. Therefore, the presence of LV

hypertrophy with another abnormality should raise the possibility of silent CAD. Such echocardiographic alterations may indicatetheroleofischemicdiseaseinLV remodeling and a potentially increased risk of HF.

Diagnosis of heart failure

According to the recent guidelines of the European Society of Cardiology (ESC),

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Symptoms and signs of HF NT-proBNP ≥ 125 ng/l or BNP ≥ 35 ng/l

Cardiac imaging EF

Cardiac remodeling Left atrial pressure

Relaxation

HFrEF, HFpEF, or HFmrEF

Known symptomatic CAD Hypertension

Known silent CAD detected on Q waves or previous screening tests:

- stress ECG test or myocardial perfusion imaging or stress

echocardiography - CAC, CT angiography, or invasive

coronary angiography

CAD of insufficient severity to account for CHF

or no clear etiology of HF

Invasive coronary angiography

Revascularization in patients with high ischemic

burden

Medical treatments BP control

Statins Anti-platelet therapy

Lifestyle and patient education

Smoking cessation, weight loss, advice for diet and

encouragement to physical activity or rehabilitation

program

HFrEF 1st line: ACEI & beta-blockers

Other treatments: MRA, ARNi, Ivabradine

Devices Symptomatic (diuretics)

HFpEF: symptomatic (diuretics)

Anti-hyperglycemic therapy Avoid hypoglycemia

No glitazone SGLT2 inhibitor

or GLP1-RA except for HFrEF Metformin and insulin if

necessary

Etiological assessment

Exclusion of acute coronary syndrome (e.g. by high-sensitivity Troponin assay)

Fig. 1 8 Diagnostic andtherapeutic workflow in diabeticpatientswith congestive heart failure andsilentcoronary artery disease. ACEI angiotensin-converting enzyme inhibitors, ARNi angiotensin receptorneprilysin inhibitor, BPbloodpressure, CAC coronary artery calcium score,CAD coronary artery disease,CHF congestiveheartfailure,CT computedtomography, EF ejection fraction,HFrEF/HFpEF/HFmrEF heart failure with reduced/preserved/mid-range ejection fraction, MRA mineralo- corticoidreceptorantagonist, NT-proBNPN-terminal pro-brain natriureticpeptide,SGLT2sodium–glucose cotransporter2

chronic HF should be diagnosed in the presence of signs and symptoms, mainly dyspnea, together with evidence of ab- normal heart function (. Fig. 1). Indica- tors of cardiac dysfunction may be LVEF <40% for HF with reduced EF (HFrEF), orincreasednatriureticpeptides(NP)as- sociated with heart structural alteration and abnormal diastolic function for HF with preserved EF (HFpEF), or HF with mid-range EF (HFmrEF) [46]. The im- portance of asking questions to patients whodonotcomplainofsymptomsissup- ported by a recent study including 581 patients with T2D (mean age, 72 years, 65% with hypertension, 19% with CAD). Heart failure was systematically looked for (clinical symptoms and signs, LV dys- function on cardiac ultrasound) and di- agnosed in 28% of patients, mostly as HFpEF, with CAD being considered the most common cause after hypertension [6].

According to these recent guidelines, ECG and NP (brain natriuretic peptide [BNP] and N-terminal pro-BNP [NT- proBNP]) are first-line recommended tools; echocardiography should be per-

formed later, except if HF has been otherwise ruled out [46]. Such a strat- egy may hold limitations. First, these guidelines are focused on patients with symptomatic HF. The detection of LV dysfunction at a preclinical stage might offer the opportunity to identify earlier patients at high risk, thereby allowing preventive treatment to mitigate the prognosis, a hypothesis that warrants confirmation. Second, one should not consider that the detection of ischemia and HF should be performed separately. Biomarkers (i.e., NP) and ECG are not specific to HF, but rather offer the op- portunity to detect both ischemia (see next section) and/or HF, and therefore should be considered in all T2D patients. Third, the sensitivity of these diagnostic tools is not uniform, as for the detection of ischemia.

Both BNP and NT-proBNP are rec- ommended as first-line tools for patients with suspected HF with a threshold value of125ng/lforNT-proBNPand35ng/lfor BNP. Suchlow values offer very high sen- sitivity(94–98%)andshouldallowforthe detection of patients with symptomatic

HF but also those with LV dysfunction only [47]. Furthermore, NT-proBNP might also serve as a biomarker for silent CAD. Indeed, in asymptomatic patients with T2D, we reported that plasma NT- proBNP in the third tertile (≥38pg/ml) of our study population predicted silent CADwithasensitivityof59%andaspeci- ficity of 67%, independently of LV func- tion and structure [48].

The recommendation to perform echocardiography only when the diag- nosis remains uncertain or as a confir- mation tool may not be suitable in the specific contextofT2Dpatients. A recent echocardiographic study that included 842 patients from two distinct cohorts identified three clusters of patients [49]. Cluster 1 were patients with low comor- bidity, less myocardial hypertrophy and diastolic dysfunction, high LVEF and myocardial strain. Cluster 2 were elderly patients, predominantly female, with high blood pressure, obesity, they had the best myocardial strain but the most altered diastolic function. Cluster 3 were male patients with similar age, hyperten- sion, and obesity to cluster 1; they had

Herz 3 · 2019 213

Main topic

the maximal myocardial hypertrophy, dilatation, and reduced strain. During follow-up, clusters 2 and 3 had increased cardiovascular mortality or hospitaliza- tions[49]. Thesedatasuggestthatclinical characteristics are not accurate enough for risk stratification of patients and that a large proportion of patients should un- dergo echocardiography that is coupled with strain imaging. The large diffusion of strain imaging on most recent ultra- sound machines will allow for its general use. As cited earlier, echocardiography provides a very detailed report of cardiac alterations that includes modifications suggestive of ischemia, heart failure, and LV dysfunction in addition to strong prognostic indices. Myocardial strain imaging will improve both the detection of LV dysfunction as well as of ischemia as offered by echocardiography.

Coronary imaging is strongly recom- mended for diabetic patients without a clear etiology of HF so as to detect pre- viously unknown or silent CAD, since the finding of CAD is important not only for revascularization but for addi- tional treatments including anti-platelet therapy and statins.

Therapeutic implications

Lifestyle and medical preventive treatments in patients with silent CAD or silent HF

LikeinclinicalCAD,preventivemeasures targeting lifestyle changes need to be strongly advocated in patients with silent CAD in order to reduce the risks of ma- jor events (. Fig. 1). This includes smok- ing cessation, advice for diet, and en- couragementforphysical activity. Statins targeting low-density lipoprotein (LDL) cholesterol levels under 70mg/dl, blood pressure control, and renin-angiotensin system (RAS)inhibitors as first-line ther- apy are also logical.

The impactofa cardioprotective treat- ment has recently been suggested by the PONTIAC trial performed with high- riskT2DpatientswithNT-proBNPlevels >125ng/l but no obvious cardiac disease [50]. The T2D patients were random- ized to a control group or an intensified treatment group in which all patients

received an angiotensin-converting en- zyme (ACE) inhibitor and a beta-blocker agent. After 12 months of follow-up, the patientsintheintensifiedgrouphadmore active treatment at higher dosage and a reduction in cardiovascular mortality/ hospitalization. A confirmation study is ongoing. If the results are replicated, pa- tients should be screened and their treat- ment up-titrated based on biomarkers.

Regarding aspirin, the ASCEND trial [51] has recently shown that in diabetic patients older than 40 years in primary prevention, aspirin decreases the rate of cardiovascular events but is associated with a clear increase in major bleeding, resulting in a nonsignificant difference in overall mortality. Thus, the system- atic use of low-dose aspirin should not be recommended in diabetic patients in primary prevention. A possible benefi- cial effect in very high-risk patients such as those with silent myocardial ischemia is unknown and has to be specifically studied.

Impact of coronary revascular- ization in patients with silent CAD

In the Swedish heart failure registry from 2003to2011, theimpactofischemicheart disease onmortalityinpatients withT2D was beneficially influenced by previous revascularization[15]. Asaconsequence, the adequate identification of patients with silent CAD is pivotal. Some ran- domized clinical trials have evaluated the impact of screening for silent myocardial ischemia in diabetic patients and showed no differences in cardiac death and un- stable angina at follow-up in those who underwent stress testing or CT coronary angiography compared with the current standard of care based on the strict con- trol of risk factors [39, 52]. However, in a meta-analysis of five randomized con- trolled trials including 3299 participants, there was a trend with screening toward a nonsignificant reduction in event rates of nonfatal myocardial infarction (rela- tive risk, 0.65; p= 0.062) and hHF (rel- ative risk, 0.61; p= 0.1) [53]. This result deserves being tested in larger, appro- priately powered trials, and the benefit of coronary revascularization in patients

withsilentmyocardialinfarctionorsilent myocardial ischemia needs to be evalu- ated specifically.

Effect of glycemic control in diabetic patients with silent CAD

In the UKPDS epidemiological analysis, a 1% drop in HbA1c levels was associated with a 16% reduction in HF risk [54]. In a pilot study, improvement of glycemic control with insulin therapy was sug- gested to improve myocardial diastolic function and perfusion in T2D patients [55]. However, a meta-analysis of ran- domized trials of intensive glucose treat- ment did not show any benefit of inten- sive treatment on the reduction of either hHF-orHF-relatedmortality[56]. Inthe Veterans Affairs Diabetes Trial, intensive glucose-lowering therapy reduced CVD events only in patients with a CAC score of <100 AU, which suggests a lack of benefit in those with silent CAD [57]. When targeting a stricter glycemic con- trol, avoidanceofhypoglycemiaiscrucial in patients with silent as well as clinical CAD and in HF patients, as it was shown to be detrimental, in order to avoid sym- pathetic activation and reduce the risk of arrhythmia and recurrent congestive episodes.

A more novel issue concerns the spe- cific effects of antihyperglycemic medi- cations on CVD events. Insulin seems to be a good choice in diabetic patients withcongestiveHF.IntheORIGINstudy, insulin glargine treatment at a moderate dose was not associated with a higher risk of cardiovascular complications in- cluding HF [58]. Regarding other “old” antihyperglycemic classes, observational studies have shown that the HF inci- dencewaslowerinpatientsonmetformin treatment compared with sulfonylureas. In the REACH registry including thou- sands of diabetic patients with diffuse ar- terial disease, patients on metformin had a 33% lower mortality and the results re- mained significant in patients with HF [59]. Metformin is no longer contraindi- cated in patients with congestive HF pro- vided they do not have advanced kidney failure. Glitazones often induce edema and, in particular in patients with pre- vious myocardial infarction and/or HF,

214 Herz 3 · 2019

can lead to congestive HF, subsequently to increased renal sodium tubular reab- sorption and hypervolemia [60]; they are contraindicated in patients with clinical HF[46]. Ameta-analysisincludingseven randomized double-blind trials reported a 45% reduction in the relative risk of HF with acarbose versus placebo in patients with T2D [61].

In most of the recent CVOTs, more than 50% of the T2D patients included had CAD. Regarding dipeptidyl pep- tidase-4 (DPP4) inhibitors, only the SAVOR trial that tested saxagliptin re- ported an increase (+27%) in the rate of hHF, mostly in patients with a history of HF or elevated plasma pro-BNP levels [62], while in the TECOS study there was no concern about an increase in hHF with sitagliptin [63]. Glucagon- like peptide 1 (GLP-1) receptor ago- nists showed a significant reduction of major events with liraglutide in the LEADER study [64], with semaglutide in the SUSTAIN-6 study [65], and with albiglutide in the HARMONY study [66] but they had no effect on hHF. How- ever, in two recent studies in patients with HFrEF, cardiovascular prognosis was impaired in patients on liraglu- tide [67, 68]. Testing sodium–glucose co-transporter (SGLT2) inhibitors, the EMPA-REG OUTCOME study (with empagliflozin) and the CANVAS study (with canagliflozin) both showed a 35% drop in hHF rate [69, 70], which resulted mainly from volume depletion.

In clinical practice, the glycemic con- trol target should be defined on an in- dividual basis, considering the presence and severity of CAD and the risk of hy- poglycemia. In our opinion, diabetic pa- tients with silent CAD should be con- sidered as in secondary prevention, and treatments with risk for hypoglycemia (sulfonylureas, glinides, insulin) should be avoided if possible. It is now time, as stated in the new European Association for the Study of Diabetes and the Amer- ican Diabetes Association (EASD-ADA) guidelines [70], to favor the use of an- tihyperglycemic drugs that have shown clearbenefitsintermsofreductionofma- jor cardiovascular events, such as liraglu- tideandsemaglutidethatdecreasemostly atherosclerotic outcomes and SGLT2 in-

hibitors that decrease mostly the risk for HF.

Conclusion

Diabetic patients with unknown CAD, silent myocardial infarction, or silent myocardial ischemia should be screened for asymptomatic changes in LV function or structure. All the risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction. In patients with congestive HF and no obvious cause of HF, invasive coronary angiog- raphy (or noninvasive CT angiography) should be performed to detect CAD, since the finding of CAD may involve revascularization and requires addi- tional treatments including antiplatelet agents and statins.

Corresponding address

Prof. P. Valensi Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH- IdF, CINFO, Paris Nord University avenue du 14 Juillet, 93140 Bondy, France [email protected]

Compliance with ethical guidelines

Conflict of interest P.Valensihasreceivedspeaker feesfromAbbott,AstraZeneca,Bayer,Eli-Lilly,Glaxo- SmithKline,MerckSanté,Merck-SharpDohme,Novo- Nordisk,PierreFabreandSanofi-Aventis, research grantsfromAbbott,AstraZeneca,BristolMyersSquibb, GlaxoSmithKline,MerckSanté,Merck-SharpDohme andNovo-Nordisk,andreportsparticipationinEx- pertsCommitteesforAbbott,Amgen,AstraZeneca, Boehringer-Ingelheim,Daichi-Sankyo,GlaxoSmithK- line,Kowa,Merck-SharpDohme,Novo-Nordisk, Sanofi-Aventis. C.Meunehasreceivedspeakerfees fromBayer,Biomérieux,BristolMyersSquibb,Novar- tis,RocheDiagnosticsandreportsparticipationin ExpertsCommitteesforBayer,Biomérieux,Servier, Novartis,RocheDiagnostics.

Forthisarticlenostudieswithhumanparticipants oranimalswereperformedbyanyoftheauthors. All citedstudieswereperformedinaccordancewiththe ethicalstandardsindicatedineachpublication.

References

1. Kannel WB, Hjortland M, Castelli WP (1974) Role of diabetes in congestive heart failure: the Framinghamstudy.AmJCardiol34(1):29–34

2. Thrainsdottir IS, Aspelund T, Thorgeirsson G et al (2005) The association between glucose abnor- malities and heart failure in the population-based Reykjavikstudy.DiabetesCare28(3):612–616

3. de Simone G, Devereux RB, Chinali M et al (2010) Diabetesandincidentheartfailureinhypertensive andnormotensiveparticipantsoftheStrongHeart Study.JHypertens28(2):353–360.https://doi.org/ 10.1097/HJH.0b013e3283331169

4. StandlE,SchnellO,McGuireDK(2016)Heartfailure considerations of antihyperglycemic medications for type 2 diabetes. Circ Res 118(11):1830–1843. https://doi.org/10.1161/CIRCRESAHA.116.306924

5. Rawshani A, Rawshani A, Franzen S et al (2017) Mortalityandcardiovasculardiseaseintype1and type2diabetes. N EnglJMed376(15):1407–1418. https://doi.org/10.1056/NEJMoa1608664

6. Boonman-de Winter LJ, Rutten FH, Cramer MJ et al (2012) High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes. Diabetologia 55(8):2154–2162. https://doi.org/ 10.1007/s00125-012-2579-0

7. CowieMR,WoodDA,CoatsAJetal(1999)Incidence andaetiologyofheartfailure; apopulation-based study.EurHeartJ20(6):421–428

8. Nichols GA, Hillier TA, Erbey JR, Brown JB (2001) Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care24(9):1614–1619

9. Zelniker TA, Wiviott SD, Raz I et al (2019) SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta- analysis of cardiovascular outcome trials. Lancet 393(10166):31–39. https://doi.org/10.1016/ S0140-6736(18)32590-X

10. Dinh W, Futh R, Lankisch M et al (2011) Cardio- vascularautonomicneuropathycontributestoleft ventricular diastolic dysfunction in subjects with type 2 diabetes and impaired glucose tolerance undergoing coronary angiography. Diabet Med 28(3):311–318. https://doi.org/10.1111/j.1464- 5491.2010.03221.x

11. Tribouilloy C, Rusinaru D, Mahjoub H et al (2008) Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study. Heart 94(11):1450–1455. https://doi.org/10.1136/hrt. 2007.128769

12. Targher G, Dauriz M, Laroche C et al (2017) In- hospital and 1-year mortality associated with diabetes in patients with acute heart failure: results from the ESC-HFA Heart Failure Long-Term Registry. Eur J Heart Fail 19(1):54–65. https://doi. org/10.1002/ejhf.679

13. Dauriz M, Targher G, Laroche C et al (2017) Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry.DiabetesCare40(5):671–678.https://doi. org/10.2337/dc16-2016

14. Cavender MA, Steg PG, Smith SC Jr et al (2015) Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH)

Herz 3 · 2019 215

Main topic

Registry. Circulation132(10):923–931. https://doi. org/10.1161/CIRCULATIONAHA.114.014796

15. Johansson I, Dahlstrom U, Edner M et al (2016) Prognosticimplicationsoftype2diabetesmellitus in Ischemic and nonischemic heart failure. J Am CollCardiol68(13):1404–1416. https://doi.org/10. 1016/j.jacc.2016.06.061

16. PrideYB,PiccirilloBJ,GibsonCM(2013)Prevalence, consequences, and implications for clinical trials of unrecognized myocardial infarction. Am J Cardiol 111(6):914–918. https://doi.org/10.1016/ j.amjcard.2012.11.042

17. Valensi P, Lorgis L, Cottin Y (2011) Prevalence, incidence, predictive factors and prognosis of silent myocardial infarction: a review of the literature. Arch Cardiovasc Dis 104(3):178–188. https://doi.org/10.1016/j.acvd.2010.11.013

18. Burgess DC, Hunt D, Li L et al (2010) Incidence and predictors of silent myocardial infarction in type 2 diabetes and the effect of fenofibrate: an analysis from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Eur Heart J 31(1):92–99. https://doi.org/10.1093/ eurheartj/ehp377

19. MacDonald MR, Petrie MC, Home PD et al (2011) Incidence and prevalence of unrecognized myocardial infarction in people with diabetes: a substudy of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) Study. Diabetes Care 34(6):1394–1396. https://doi.org/10.2337/dc10- 2398

20. QureshiWT,ZhangZM,ChangPPetal(2018)Silent myocardial infarction and long-term risk of heart failure:theARICStudy. JAmCollCardiol71(1):1–8. https://doi.org/10.1016/j.jacc.2017.10.071

21. Kondola S, Davis WA, Dembo LG, Davis TM (2008) A cardiac magnetic resonance imaging study of electrocardiographic Q waves in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Res Clin Pract 82(1):87–92. https://doi.org/10.1016/j. diabres.2008.06.016

22. Amier RP, Smulders MW, van der Flier WM et al (2018) Long-term prognostic implications of previous silent myocardial infarction in patients presentingwithacutemyocardialinfarction. JACC Cardiovasc Imaging 11(12):1773–1781. https:// doi.org/10.1016/j.jcmg.2018.02.009

23. Kannel WB, Cupples LA, Gagnon DR (1990) Inci- dence, precursors and prognosis of unrecognized myocardial infarction. Adv Cardiol 37:202–214. https://doi.org/10.1159/000418828

24. CossonE,GuimfackM,PariesJetal(2003)Aresilent coronarystenosespredictableindiabeticpatients andpredictiveofcardiovascularevents? Diabetes Metab29(5):470–476

25. Valensi P, Cosson E (2010) It is not yet the time to stop screening diabetic patients for silent myo- cardial ischaemia. Diabetes Metab 36(2):91–96. https://doi.org/10.1016/j.diabet.2010.01.001

26. Wackers FJ, Young LH, Inzucchi SE et al (2004) Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD Study. DiabetesCare27(8):1954–1961

27. Zellweger MJ, Maraun M, Osterhues HH et al (2014) Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomizedtreatmentsubstudy. JACCCardiovasc Imaging 7(10):1001–1010. https://doi.org/10. 1016/j.jcmg.2014.07.010

28. SultanA,PerriardF,MacioceVetal(2017)Evolution of silent myocardial ischaemia prevalence and

cardiovascular disease risk factor management in type 2 diabetes over a 10-year period: an observationalstudy.DiabetMed34(9):1244–1251. https://doi.org/10.1111/dme.13364

29. Cosson E, Paycha F, Paries J et al (2004) Detecting silent coronary stenoses and stratifying cardiac risk in patients with diabetes: ECG stress test or exercise myocardial scintigraphy? Diabet Med 21(4):342–348. https://doi.org/10.1111/j.1464- 5491.2004.01157.x

30. Nguyen MT, Pham I, Valensi P et al (2014) Flow-mediated-paradoxical vasoconstriction is independently associated with asymptomatic myocardial ischemia and coronary artery disease in type 2 diabetic patients. Cardiovasc Diabetol 13:20.https://doi.org/10.1186/1475-2840-13-20

31. Nitenberg A, Valensi P, Sachs R et al (1993) ImpairmentofcoronaryvascularreserveandACh- inducedcoronaryvasodilationindiabeticpatients with angiographically normal coronary arteries and normal left ventricular systolic function. Diabetes42(7):1017–1025

32. Pham I, Nguyen MT, Valensi P et al (2015) Noninvasive study of coronary microcirculation response to a cold pressor test. Eur J Clin Invest 45(2):135–143.https://doi.org/10.1111/eci.12389

33. Raggi P, Shaw LJ, Berman DS, Callister TQ (2004) Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol 43(9):1663–1669. https://doi. org/10.1016/j.jacc.2003.09.068

34. ValentiV,HartaighBO,ChoIetal(2016)Absenceof coronary artery calcium identifies asymptomatic diabetic individuals at low near-term but not long-term risk of mortality: a 15-year follow- up study of 9715 patients. Circ Cardiovasc Imaging 9(2):e3528. https://doi.org/10.1161/ CIRCIMAGING.115.003528

35. Anand DV, Lim E, Hopkins D et al (2006) Risk stratification in uncomplicated type 2 diabetes: prospectiveevaluationofthecombined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy. Eur Heart J 27(6):713–721. https://doi.org/10.1093/ eurheartj/ehi808

36. Ryden L, Grant PJ, Anker SD et al (2013) ESC guidelines on diabetes, pre-diabetes, and cardiovasculardiseasesdevelopedincollaboration with the EASD: the task force on diabetes, pre- diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 34(39):3035–3087. https://doi.org/10. 1093/eurheartj/eht108

37. SolimanEZ(2018)Silentmyocardialinfarctionand risk of heart failure: current evidence and gaps in knowledge. Trends Cardiovasc Med. https://doi. org/10.1016/j.tcm.2018.09.004

38. Cosson E, Guimfack M, Paries J et al (2003) Prognosis for coronary stenoses in patients with diabetesandsilentmyocardialischemia. Diabetes Care26(4):1313–1314

39. YoungLH,WackersFJ,ChyunDAetal(2009)Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: theDIADstudy: arandomizedcontrolled trial. JAMA 301(15):1547–1555. https://doi.org/ 10.1001/jama.2009.476

40. Cosson E, Nguyen MT, Chanu B et al (2011) Cardiovascular risk prediction is improved by adding asymptomatic coronary status to routine risk assessment in type 2 diabetic patients.

Diabetes Care 34(9):2101–2107. https://doi.org/ 10.2337/dc11-0480

41. Valensi P, Sachs RN, Harfouche B et al (2001) Predictivevalueofcardiacautonomicneuropathy indiabeticpatientswithorwithoutsilentmyocar- dialischemia.DiabetesCare24(2):339–343

42. Fox KF, Cowie MR, Wood DA et al (2001) Coronary arterydiseaseasthecauseofincidentheartfailure in the population. Eur Heart J 22(3):228–236. https://doi.org/10.1053/euhj.2000.2289

43. Kosuga T, Komukai K, Miyanaga S et al (2016) Diabetes is a predictor of coronary arterystenosis in patients hospitalized with heart failure. Heart Vessels 31(5):671–676. https://doi.org/10.1007/ s00380-015-0669-x

44. Nguyen MT, Cosson E, Valensi P et al (2011) Transthoracic echocardiographic abnormalities in asymptomatic diabetic patients: association with microalbuminuria and silent coronary artery disease. Diabetes Metab 37(4):343–350. https:// doi.org/10.1016/j.diabet.2010.12.006

45. Pham I, Cosson E, Nguyen MT et al (2015) Evidence for a specific diabetic cardiomyopathy: anobservationalretrospectiveechocardiographic study in 656 asymptomatic type 2 diabetic patients. IntJEndocrinol2015:743503. https://doi. org/10.1155/2015/743503

46. PonikowskiP,VoorsAA,AnkerSDetal(2016)2016 ESC guidelinesfor the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heartfailureoftheEuropeanSocietyofCardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200. https://doi.org/10. 1093/eurheartj/ehw128

47. McDonaghTA,HolmerS,RaymondIetal(2004)NT- proBNPandthediagnosisofheartfailure:apooled analysis of three European epidemiological studies. Eur J Heart Fail 6(3):269–273. https://doi. org/10.1016/j.ejheart.2004.01.010

48. Cosson E, Nguyen MT, Pham I et al (2009) N-terminal pro-B-type natriuretic peptide: an independent marker for coronary artery disease in asymptomatic diabetic patients. Diabet Med 26(9):872–879. https://doi.org/10.1111/j.1464- 5491.2009.02788.x

49. ErnandeL,AudureauE,JellisCLetal(2017)Clinical implications of echocardiographic phenotypes of patients with diabetes mellitus. J Am Coll Cardiol 70(14):1704–1716. https://doi.org/10.1016/j.jacc. 2017.07.792

50. Huelsmann M, Neuhold S, Resl M et al (2013) PONTIAC (NT-proBNP selected prevention of cardiaceventsinapopulationofdiabeticpatients withoutahistoryofcardiacdisease): aprospective randomized controlled trial. J Am Coll Cardiol 62(15):1365–1372. https://doi.org/10.1016/j.jacc. 2013.05.069

51. Bowman L, Mafham M, Wallendszus K et al (2018) Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 379(16):1529–1539. https://doi.org/10.1056/ NEJMoa1804988

52. Muhlestein JB, Lappe DL, Lima JA et al (2014) Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA 312(21):2234–2243. https://doi.org/10.1001/ jama.2014.15825

53. ClercOF,FuchsTA,StehliJetal(2018)Non-invasive screening for coronary artery disease in asymp- tomatic diabetic patients: a systematic review

216 Herz 3 · 2019

andmeta-analysisofrandomisedcontrolledtrials. Eur Heart J Cardiovasc Imaging 19(8):838–846. https://doi.org/10.1093/ehjci/jey014

54. Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS35): prospectiveobservationalstudy. BMJ 321(7258):405–412

55. von Bibra H, Hansen A, Dounis V et al (2004) Augmented metabolic control improves myocar- dial diastolic function and perfusion in patients with non-insulin dependent diabetes. Heart 90(12):1483–1484. https://doi.org/10.1136/hrt. 2003.020842

56. Control G, Turnbull FM, Abraira C et al (2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52(11):2288–2298. https://doi.org/10.1007/ s00125-009-1470-0

57. Reaven PD, Moritz TE, Schwenke DC et al (2009) Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetestrialparticipantswithlowercalcifiedcoro- nary atherosclerosis. Diabetes 58(11):2642–2648. https://doi.org/10.2337/db09-0618

58. Gerstein HC, Miller ME, Ismail-Beigi F et al (2014) Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet 384(9958):1936–1941. https://doi.org/10.1016/ S0140-6736(14)60611-5

59. Roussel R, Travert F, Pasquet B et al (2011) Metforminuseandmortalityamongpatientswith diabetes and atherothrombosis. Arch Intern Med 170(21):1892–1899

60. Erdmann E, Charbonnel B, Wilcox RG et al (2007) Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease:datafromthePROactivestudy(PROactive 08). DiabetesCare30(11):2773–2778. https://doi. org/10.2337/dc07-0717

61. Hanefeld M, Cagatay M, Petrowitsch T et al (2004) Acarbosereducestheriskformyocardialinfarction intype2diabeticpatients: meta-analysisofseven long-termstudies.EurHeartJ25(1):10–16

62. Scirica BM, Braunwald E, Raz I et al (2014) Heart failure, saxagliptin, and diabetes mellitus: observationsfromtheSAVOR-TIMI53randomized trial. Circulation 130(18):1579–1588. https://doi. org/10.1161/CIRCULATIONAHA.114.010389

63. McGuire DK, Van de Werf F, Armstrong PW et al (2016) Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial. JAMA Cardiol 1(2):126–135. https://doi.org/10.1001/ jamacardio.2016.0103

64. Marso SP, Daniels GH, Brown-Frandsen K et al (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375(4):311–322. https://doi.org/10.1056/NEJMoa1603827

65. Marso SP, Bain SC, Consoli A et al (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375(19):1834–1844. https://doi.org/10.1056/ NEJMoa1607141

66. Hernandez AF, Green JB, Janmohamed S et al (2018)Albiglutideandcardiovascularoutcomesin patients with type 2 diabetes and cardiovascular disease (harmony outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392(10157):1519–1529. https://doi.org/10.1016/ S0140-6736(18)32261-X

67. Margulies KB, Hernandez AF, Redfield MM et al (2016) Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 316(5):500–508. https://doi.org/10. 1001/jama.2016.10260

68. Jorsal A, Kistorp C, Holmager P et al (2017) Effect ofliraglutide,aglucagon-likepeptide-1analogue, on left ventricular function in stable chronic heart failurepatientswithandwithoutdiabetes(LIVE)-a multicentre, double-blind, randomised, placebo- controlled trial. Eur J Heart Fail 19(1):69–77. https://doi.org/10.1002/ejhf.657

69. Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117–2128. https://doi.org/10.1056/ NEJMoa1504720

70. Davies MJ, D’Alessio DA, Fradkin J et al (2018) Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61(12):2461–2498. https:// doi.org/10.1007/s00125-018-4729-5

Fachnachrichten

Weniger Medizintouristen

ImJahr2017ließensichrund247.500 Patienten aus 177 Ländern statio- när oder ambulant in Deutschland behandeln und bescherten dem Ge- sundheitssystem Einnahmen von etwa 1,2 Milliarden Euro.

Das entspreche einem Rückgang der Pati- enten aus dem Ausland von 2% gegenüber

Vorjahr, konstatierte Jens Juszczak von der Hochschule Bonn-Rhein-Sieg (H-BRS).

Hauptgrund sei erneut ein massiver Ein-

bruch der Behandlungsreisen aus einigen Golfstaaten: Kuwait (-62 %), Saudi-Arabien

(-36 %) und Oman (-28 %). In den einst

spendablen arabischen Ländern finde der- zeit ein Umdenken statt. Die Kostenträger

kontrollierten Rechnungen deutscher Ärz- te und Klinikenjetzt viel genauerund sank-

tionierten Verstöße. Den Einrichtungen im

Akut- und Rehabilitationsbereich drohten zudem lange Wartezeitenauf ausstehende

Beträge oder gar Rückforderungen zuviel

gezahlter Gelder, Provisionszahlungen an Patientendienstleistereingeschlossen.

Zwei Bundesländer stärker betroffen

Am stärksten Auslandspatienten verloren haben demnach Berlin (-14 %) und Baden-

Württemberg (-9 %), die Nachfrage aus der

Golfregion halbierte sich dort. Besonders aus Kuwait (-79 % bzw. -70 %) kamen

deutlich weniger Patienten. Speziell aus- gebildetes Personal, gute Kontakte in die

Zielländer und regelmäßige Kontrolle aller

Aktivitäten im internationalen Geschäft seien wichtige Voraussetzungen für Erfolg

im Medizintourismus,meint Juszczak.

Lichtblick russischsprachige Länder

Im russischsprachigen Markt zeichne sich

im Gegensatz zu den Golfstaaten ein Licht-

blick ab. Die meisten Mitgliedstaaten der GUS entwickelten sich wieder positiv –

allen voran Russland (+8 %), die Ukraine

(+19 %) und Kasachstan (+ 37%). Aus der Russischen Föderation kommen laut Jusz-

czak mittlerweile mehr Patienten als aus allen Golfstaaten zusammen.

Quelle: Hochschule Bonn-Rhein-Sieg www.h-brs.de

Herz 3 · 2019 217

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