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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

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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

https://doi.org/10.1007/s00059-019-4798-3

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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),

    212 Herz 3 · 2019

    https://doi.org/10.1007/s00059-019-4798-3

    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
    paul.valensi@aphp.fr

    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.

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    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

    https://doi.org/10.1093/ehjci/jey014

    https://doi.org/10.1136/hrt.2003.020842

    https://doi.org/10.1136/hrt.2003.020842

    https://doi.org/10.1007/s00125-009-1470-0

    https://doi.org/10.1007/s00125-009-1470-0

    https://doi.org/10.2337/db09-0618

    https://doi.org/10.1016/S0140-6736(14)60611-5

    https://doi.org/10.1016/S0140-6736(14)60611-5

    https://doi.org/10.2337/dc07-0717

    https://doi.org/10.2337/dc07-0717

    https://doi.org/10.1161/CIRCULATIONAHA.114.010389

    https://doi.org/10.1161/CIRCULATIONAHA.114.010389

    https://doi.org/10.1001/jamacardio.2016.0103

    https://doi.org/10.1001/jamacardio.2016.0103

    https://doi.org/10.1056/NEJMoa1603827

    https://doi.org/10.1056/NEJMoa1607141

    https://doi.org/10.1056/NEJMoa1607141

    https://doi.org/10.1016/S0140-6736(18)32261-X

    https://doi.org/10.1016/S0140-6736(18)32261-X

    https://doi.org/10.1001/jama.2016.10260

    https://doi.org/10.1001/jama.2016.10260

    https://doi.org/10.1002/ejhf.657

    https://doi.org/10.1056/NEJMoa1504720

    https://doi.org/10.1056/NEJMoa1504720

    https://doi.org/10.1007/s00125-018-4729-5

    https://doi.org/10.1007/s00125-018-4729-5

    Reproduced with permission of copyright owner. Further reproduction
    prohibited without permission.

      Congestive heart failure caused by silent ischemia and silent myocardial infarction
      Abstract
      Zusammenfassung
      Heart failure in patients with CAD and diabetes
      Silent CAD and risk of heart failure in diabetic patients
      High prevalence of silent CAD in diabetes
      Prognosis of silent CAD in diabetic patients and risk of HF
      Association between silent CAD and echocardiographic changes
      Diagnosis of heart failure
      Therapeutic implications
      Lifestyle and medical preventive treatments in patients with silent CAD or silent HF
      Impact of coronary revascularization in patients with silent CAD
      Effect of glycemic control in diabetic patients with silent CAD
      Conclusion
      References

    Prince George’s Community College

    Department of Nursing

    NUR 1020: Library Assignment

    Lesson Objectives:

    1. Choose a topic from the list below

    2. Print a copy of an article chosen from a nursing journal* related to your topic

    3. Create a reference page in APA format for the chosen article

    4. Provide a 1page summary of the article

    5. Upload a copy of the article and summary to blackboard by week 6 . This is due on your clinical day during week 6.

    *The journal must be peer-reviewed, written by a nurse within the last 5 years *

    Topics:

    1. Hypertension

    2. Diabetes

    3. Congested Heart Failure

    4. Client Education

    5. Safe medication administration, Choose two from below

    1. Oral Medication

    2. Intramuscular

    3. Subcutaneous

    4. Intravenous

    6. Restraints

    7. Mobility or immobility and nursing care

    1. What is recommended in the literature for post- surgical clients

    8. Pressure sores and/or wound care

    1. Prevention

    2. Management

    9. Fluid and Electrolytes   

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