life
Article
Pulmonary Artery Pressure-Guided Telemonitoring Reduced
Pulmonary Artery Pressure but Did Not Result in Higher Doses
of Guideline-Directed Medical Therapy–Observations from an
Advanced Elderly German Heart Failure Cohort
Ester J. Herrmann 1,† , Badrinarayanan Raghavan 1,† , Nina Eissing 2, Stephan Fichtlscherer 2,3,
Christian W. Hamm 1,3 and Birgit Assmus 1,2,3,*
1 Department of Medicine I, Cardiology, University Hospital Giessen and Marburg, 35392 Giessen, Germany;
ester.herrmann@innere.med.uni-giessen.de (E.J.H.);
badrinarayanan.raghavan@innere.med.uni-giessen.de (B.R.);
christian.hamm@innere.med.uni-giessen.de (C.W.H.)
2 Department of Medicine III, Cardiology, University Hospital Frankfurt am Main, 60590 Frankfurt am Main,
Germany; ninas@eissing.net (N.E.); fichtlscherer@em.uni-frankfurt.de (S.F.)
3 German Center for Cardiovascular Research, DZHK, 10115 Berlin, Germany
* Correspondence: birgit.assmus@innere.med.uni-giessen.de
† These authors contributed equally to this work.
Abstract: Introduction: Remote pulmonary artery pressure (PAP)-guided heart failure (HF) therapy
for NYHA class III patients has been shown to reduce hospitalizations and increase survival. We
Citation: Herrmann, E.J.; Raghavan, aimed to assess whether PAP monitoring allows for the increase in HF directed medication in an
B.; Eissing, N.; Fichtlscherer, S.; elderly German cohort of advanced HF patients already receiving clinically optimized HF medication.
Hamm, C.W.; Assmus, B. Pulmonary Methods: We analyzed PAP and HF medication dosage, including diuretics, in 24 patients (mean
Artery Pressure-Guided age, 76 years) using implanted PAP-sensors during the first 12 months of PAP-guided HF care in an
Telemonitoring Reduced Pulmonary
interdisciplinary HF unit. Results: During 12 months of PAP-guided HF therapy, PAP decreased
Artery Pressure but Did Not Result in
significantly (4PAP systolic–6 ± 10, 4PAP diastolic–4 ± 7, 4PAP mean–4 ± 8 mm Hg, p < 0.01
Higher Doses of Guideline-Directed
Medical Therapy–Observations from for all). 16% of patients had an unplanned HF hospitalization. There was no significant change
an Advanced Elderly German Heart over time with respect to the dosage of RAAS inhibitors (ACE-I/ARB/ARNI), Beta blockers, or
Failure Cohort. Life 2022, 12, 766. MRA treatments. In contrast, the dosage of loop diuretics increased significantly (2.1 ± 0.5-fold)
https://doi.org/10.3390/ over time. In the comparison of a “responder” (patients with PAP and diuretic dose decline) and
life12050766 “non-responder” (patients with PAP and diuretic dose increase) group, there were no significant
differences between any of the baseline, medication, or HF hospitalization characteristics between
Academic Editor: Satoshi Akagi
the two groups. Conclusions: In elderly patients treated with clinically optimized HF medication, no
Received: 11 April 2022 further evidence-based medication increase could be achieved using PAP-guided HF care. However,
Accepted: 19 May 2022 by individual adjustment of diuretic dosage, a significant decline in PAP over time occurred, which
Published: 21 May 2022 could not be predicted by any of the baseline characteristics.
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in Keywords: chronic heart failure; older patients; remote monitoring; pulmonary artery pressure;
published maps and institutional affil- uptitration; guideline-directed medical therapy
iations.
1. Introduction
Copyright: © 2022 by the authors.
With 15 million patients, chronic heart failure (HF) HF is a very common disease in
Licensee MDPI, Basel, Switzerland.
This article is an open access article Europe and is the most frequent reason for a hospitalization due to illness. Because of
distributed under the terms and progressive aging in Western societies, the prevalence increases steadily and leads to a
conditions of the Creative Commons high financial burden [1–5]. Symptoms of HF include reduced exercise tolerance, which
Attribution (CC BY) license (https:// is associated with increased (left ventricular) filling pressure with the passive backward
creativecommons.org/licenses/by/ transmission of elevated pressure into the pulmonary vasculature [6,7]. Cardiopulmonary
4.0/).
Life 2022, 12, 766. https://doi.org/10.3390/life12050766 https://www.mdpi.com/journal/life
Life 2022, 12, 766 2 of 12
congestion leads to an increased pulmonary arterial pressure (PAP). Diuretics are recom-
mended to reduce the signs/symptoms of congestion. The quality of evidence regarding
diuretics is poor, and their effects on morbidity and mortality have not been studied in
randomized controlled trials (RCTs) [6], but the treatment with diuretics is mandatory to
reduce hospitalizations [8]. Standard HF medications, such as beta blockers, angiotensin-
converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), aldosterone
antagonists, angiotensin receptor-neprilysin inhibitors (ARNI), and sodium-glucose co-
transporter 2 inhibitors (SGLT2 inhibitors) all improved survival [9–15] rates, prevented
recurrent hospitalizations due to worsening HF, and improved the clinical status, functional
capacity, and quality of life [6]. However, the target dose of evidence-based medication
is generally difficult to reach outside of clinical trials [16], and elderly patients are even
less likely to receive evidence-based HF therapy [17]. Previous analyses have shown that
prevalent comorbidities and associated multi-drug treatments are the most prominent
factors limiting uptitration in elderly people [18].
During the last 15 years, with the development of a battery-free sensor for the wireless
transmission of PAP values by remote access from the patient’s home [19], clinical trials
have demonstrated that ambulatory guidance of HF treatment using PA-pressure values
resulted in reduced numbers of HF-related hospitalizations and improvement in NYHA
class and quality of life [20].
The most detailed medication analysis so far comes from the randomized CHAMPION
trial [21], where the analysis of medication changes revealed that diuretics were changed
most frequently from all drug classes, and significantly more often in the PAP-treatment
group compared to the control group. The daily diuretic dose increased significantly
within 6 months in both the control and PAP-guided treatment group, whereas doses
of neurohormonal antagonists, such as ACE-I or ARB, beta blockers, and aldosterone
receptor antagonists increased significantly by 4 mg, enalapril-equivalent, 3 mg, carvedilol-
equivalent, and 4 mg, spironolactone-equivalent in the PAP-guided treatment group, but
not in the control group. In the control and intervention group, guideline-recommended
doses could not be achieved for any of the medications.
The aim of the present early single center study was to assess whether in advanced
elderly HF patients with already clinically optimized medical HF therapy at a tertiary care
center in Germany, a further increase in evidence-based HF medication is possible with the
support of PAP hemodynamic information during a period of 12 months.
2. Methods
Patients in the HF outpatient department, with chronic HF in functional NYHA class
III, individually optimized HF medication, and a cardiac decompensation within the last
12 months, were offered implantation of the PAP sensor CardioMEMS™ and participation
in a single center telemonitoring registry. A total of 31 patients received implantation of
a CardioMEMS™ sensor via right heart catheterization between 2015 and 2017 and were
repeatedly trained in HF care by a European Society of Cardiology-certified HF nurse.
However, only 30 patients were compliant after implantation and regularly (≥5 times per
week) transmitted their data by 12 a.m. each day within 12 months of follow-up, or until
initiation of palliative care or death. A total of 24 patients survived 12 months of follow-up
and thus represent the present analysis cohort.
2.1. Hemodynamic Telemonitoring and Follow-Up
Regular telephone contact was initiated by HF nurses with all patients, using a
standardized questionnaire [adopted from the INH (Interdisciplinary Network for HF)
trial] [22]. The nurses were supported by an HF specialist. According to the telemedi-
cal standard operating procedure, weekly telephone contacts were scheduled in the first
4 weeks after implantation, followed by contacts every two weeks from week 5 to week
8 after implantation, and a routine call every 4 weeks from week 9 onward, if no alerts
occurred due to the crossing of the individually adapted optimal PAP target area. We
Life 2022, 12, 766 3 of 12
applied the hemodynamic-guided HF management previously used in the CHAMPION
trial [23]. In brief, medication was adjusted with the aim to maintain the diastolic PAP
in the range of 8–15 mmHg (optivolemic state), with the goal to first increase guidelines-
directed medical therapies (GDMT) up to the guideline recommended doses before the
adjustment of diuretics. If the patients showed signs of low perfusion, the reduction of
diuretics, fluid repletion, and/or the administration of inotropic agents were considered.
Pressure measurements were reviewed at least weekly in the case of optivolemia and two
to three times per week if diastolic PAP was outside the individually defined optimal range.
Regular outpatient visits were scheduled every 3 months in the HF outpatient department.
For comparison of the diuretic dose, torasemide was converted into a furosemide
equivalent by assuming a ratio of 1:4. All neurohormonal antagonist dose changes, which
were collected via telephone contact or during office visits, were transformed into % of
guideline recommended dose.
All patients provided written informed consent for participation in the single center
registry (NCT03020043). The study complies with the Declaration of Helsinki and was
approved by the local ethics committee.
2.2. Statistics
This study is a retrospective analysis of the first German experience with the hemodynamic-
guided HF care in an advanced HF cohort of a university hospital. Patient baseline characteristics
were calculated as mean and standard deviation. Dose changes for guideline-directed evidence-
based HF medication and changes in PAP values at baseline and follow-up (6 and 12 months
after the implant) were compared using a one-way ANOVA; for4PAP, a two-way ANOVA
was used. Dose changes for loop diuretics and functional NYHA class at baseline and
follow-up values (6 and 12 months after the implant) were compared using a paired t-test. A
Spearman’s statistical correlation analysis was performed for changes in loop diuretic dose
and PAP diastolic values. Statistical significance was assumed if p < 0.05, and all reported p
values are two-sided. All the statistical analyses, calculations, and graphs were performed
using GraphPad Prism software (version 9.0) for MS Windows (GraphPad Software, San
Diego, CA, USA).
3. Results
The patient baseline characteristics in Table 1 show an elderly advanced chronic HF
cohort (n = 24), mean age of 76 ± 8 years, predominantly male, and except for two patients,
all other patients suffered from HF with reduced ejection fraction (HFrEF). The other two
patients had a current LVEF of 40% with a history of a previous LVEF < 40%, so they were
included in the medication analysis.
Table 1. Baseline characteristics of n = 24 HF-patients.
Age (in years) 76 ± 8
Gender—male; female (n) 19; 5
NYHA class 3
Diabetes mellitus (%) 52
HFmrEF (n) 2
HFrEF (n) 22
ICD/CRT-D/CRT-P/PM (n) 12/6/1/3
NT-proBNP (pg/mL) 2810 ± 2809(median 1755)
Creatinine (mg/dl) 1.5 ± 0.4
N-terminal pro brain natriuretic peptide (NT-proBNP) values were elevated, and
kidney function was moderately impaired in most patients. All patients received hemody-
Life 2022, 12, 766 4 of 12
namic telemonitoring with the CardioMEMS™ system for severe NYHA class III HF. Only
21 of 24 patients were tolerating the RAAS blockade: one patient suffered from angioedema
and two patients were intolerant of any RAAS inhibition due to hypotension, in addition
to high potassium levels in one of these patients. A total of 92% of the patients took beta
blockers, and 75% were on MRA (Table 2).
Table 2. Medication at baseline.
% of Guideline
n = 24 Recommended Dose
(n = 24)
ACE-Inhibitor (ACE-I); n (%) 11 (46) 53 ± 25%
Angiotensin-receptor blocker (ARB); n (%) 4 (17) 55 + 25%
Angiotensin receptor blocker
Neprilysin inhibitor (ARNI); n (%) 6 (25) 34 ± 50%
Beta blocker (BB); n (%) 22 (92) 42 ± 12.5%
Mineralocorticoid-receptor
antagonist (MRA); n (%) 18 (75) 51 ± 50%
Loop diuretics; n (%) 22 (92) -
Overall, systolic blood pressure was within the normal range, despite advanced HF,
but the baseline PA pressure (PAP) was significantly elevated. Hemodynamic analysis
showed that a total of 17 patients suffered from pulmonary hypertension (defined by mean
PAP ≥ 25 mm Hg) [24]. Further classification revealed that n = 6 patients had isolated
postcapillary pulmonary hypertension, one patient could not be classified, and 10 patients
suffered from predominately combined pre- and postcapillary pulmonary hypertension
(Table 3).
Table 3. Hemodynamic baseline parameters.
Systolic Blood Pressure (mmHg) 116 ± 19
PAP systolic (mmHg) 48 ± 16
PAP mean (mmHg) 33 ± 12
PAP diastolic (mmHg) 24 ± 9
PCWP (mmHg) 17 ± 8
PVR (dyn*s/cm5) 317 ± 266
At 12 months follow-up, there was no significant change in the neurohormonal block-
ade dose, when compared to baseline medication (Figure 1A).
Between 2015 and 2017, ARNI was introduced into HF therapy; thus, we observed
increases in ARNI initiation and uptitration, with a parallel decline in ACEI and ARB.
However, none of these changes were significant. In contrast, the loop diuretic dose
increased significantly from the baseline to 6 months of follow-up (p = 0.034) and increased
further until 12 months of follow-up (Figure 1B).
As expected, diuretics were the drugs that were adjusted most frequently, as already
shown in previous trials (n = 317 changes within 12 months), followed by ARNI/ACE-
I/ARB (n = 24/28/18), BB (n = 57 changes), and MRA (n = 45 changes (Figure 1C)).
Most medication changes occurred within the first 3 months after implantation, demon-
strating the efforts to uptitrate medication and achieve optimized diastolic PAP (Figure 1D).
During the 12 months of PAP-guided HF management, we observed a statistically
significant improvement in functional NYHA class from baseline to 6 months (p = 0.015)
and up to 12 months of follow-up (p = 0.014; Figure 2).
LiLfei f2e022022, 21,21, 2x, F76O6R PEER REVIEW  5  o5f o1f31 2
 
90
Baseline
6 months
75 12 months
60
45
30
15
0
ACE‐I ARB ARNI BB MRA
 
(A) 
 
(B) 
350 317
300
250
200
150
100
57 45
50 28 18 24
0
ACE‐I ARB ARNI BB MRA Diuretics
 
(C) 
Figure 1. Cont.
 
% of guideline‐recommended dose
Number of changes
LLiiffee 22002222,, 1122,, x7 6F6OR PEER REVIEW  6 6oof f1132 
 
400
350
300
250
200
150
100
50
0
Quarter 1 Quarter 2 Quarter 3 Quarter 4
 
(D) 
Figure 1. (A) Course of guideline‐recommended doses of HF medication during 12 months of fol‐
lFoiwgu‐urep 1(.a(llA n).Cs.o).u (rBs)e Mofegauni dloeolipn ed-riuecroemticm deonsdee adt dboasseeslionfe,H 6F mmoendtihcsa,t iaonndd 1u2r imngon12thms ofonltlhoswo‐fufpo,l lcoawl‐-
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months of follow‐up 
Life 2022, 12, xo FfOfRo lPlEoEwR R-uEVpIE(Wto tal n = 513). (D) Cumulative medication changes per quarter during 12 m7o noft h13s  of
 
followB-eutpw.een 2015 and 2017, ARNI was introduced into HF therapy; thus, we observed 
increases  in ARNI  initiation and uptitration, with a parallel decline  in ACEI and ARB. 
However, none of these changes were significant. In contrast, the loop diuretic dose in‐
creased significantly from the baseline to 6 months of follow‐up (p = 0.034) and increased 
further until 12 months of follow‐up (Figure 1B).   
As expected, diuretics were the drugs that were adjusted most frequently, as already 
shown  in previous  trials (n = 317 changes within 12 months),  followed by ARNI/ACE‐
I/ARB (n = 24/28/18), BB (n = 57 changes), and MRA (n = 45 changes (Figure 1C)). 
Most medication  changes  occurred within  the  first  3 months  after  implantation, 
demonstrating  the efforts  to uptitrate medication and achieve optimized diastolic PAP 
(Figure 1D).   
During the 12 months of PAP‐guided HF management, we observed a statistically 
significant improvement in functional NYHA class from baseline to 6 months (p = 0.015) 
and up to 12 months of follow‐up (p = 0.014; Figure 2).   
In line with these finding, all PAP values decreased significantly, with an absolute 
reduction of systolic PA pressure of 6 mmHg (p = 0.007) and an absolute decline in dias‐
tolic PA‐pressure of 4 mmHg (p = 0.005; Figure 3A).   
In order to assess whether the change in the loop diuretic dose is associated with a 
reduction in PAP, we correlated the change in the loop diuretic dose with the change of 
diastolic PAP. However, the change of diastolic PAP did not correlate with the change in 
the loop diuretic dose at 6 months (Figure 3B), nor at 12 months (data not shown). In ad‐
dition, we could not identify any baseline clinical, hemodynamic, or laboratory character‐
istic that predicted the change in PAP or whether a patient could be classified as a “treat‐
ment responder,” defined as a patient with a PAP and diuretic dosage decrease, or a “non‐
responder,” defined as a patient with a PAP increase, despite diuretic increase.   
 
Figure 2. ChangeFsigiunreN 2Y. CHhAangcelsa sins NwYiHthAi ncla1s2s wmiothnint h1s2 mofonPtAhsP o-fg PuAidP‐egduidHeFd HthFe trhaeprayp.y. 
 
 
Number of changes
Life 2022, 12, 766 7 of 12
In line with these finding, all PAP values decreased significantly, with an absolute
Life 2022, 12, x FOR PEER REVrIEeWd uction of systolic PA pressure of 6 mmHg (p = 0.007) and an absolute decli8n  oef i1n3 diastolic
  PA-pressure of 4 mmHg (p = 0.005; Figure 3A).
 
(A) 
 
(B) 
Figure 3. Cont.
 
Life 2022, 12, 7x6 F6OR PEER REVIEW  9 8ooff  132 
 
 
(C) 
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Association between changes in loop diuretic dose (decline or increase) and diastolic PAP (decline 
o(Cr )inAcsrseoacsiea)t iaotn 6 bmetownethens icnh apnagtieesnitns lroeocpeivdiinugre utipctditorsaeti(odne colfi ndeifoferriennctr eHasFe )maenddicdaitaisotno laict 6P AmPo(ndtehcsl.i n e
or increase) at 6 months in patients receiving uptitration of different HF medication at 6 months.
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in the loop diuretic dose at 6 months (Figure 3B), nor at 12 months (data not shown).
4In. Daidsdcuitsiosino,nw  e could not identify any baseline clinical, hemodynamic, or laboratory
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“snyostne-mre swpiothn daedrv,”andceefidn cehdraosniac pHaFti,e cnotrwreiltahtiangP AthPe icnhcarneagsees, odfe gsupiidteeldiniuer‐erteiccoimncmreeansde.ed HF 
mediWcaittihonr edsopseecst dtourfiunrgth 1e2r moendtihcsa toifo fnomlloowd‐iufipca wtioitnhs P,AalPl  pcahtainengtess.w Ohuor wanearelyisnisit hiaatse dtwoor 
mupatiintr raetesudlwts:i tFhirAstR, Nit Idwemeroenisntrtahteesre tshpaot nndoe srigrnoiufipca(nFti gcuhraen3gCes) ,inw ghueriedaeslitnhee‐doitrheecrtecdh amnegdes‐
iocfaHl tFhemraedpiecas t(ioGnDcMouTl)d wneorteb peocsosrirbellea twedithw iPthAPch‐gaunigdeesdi nmPoAnPitorinlogo pind aiudrveatnicceddo sel.derly 
HF patients already receiving clinically optimized HF‐medication. According to the inclu‐
s4i.oDn icsrciutesrsiiao nof our registry, in close association with the CHAMPION trial [23], the PAP 
sensoTrh seysptreemse nhtass tbuedeyn iismapldaenstcerdip  itnivtoe preaptioernttsa bwohuot dalarielaydnyo rne-cineivvaesdiv derhuegm aondy dneavmiciec 
tmreoantmitoernintsg fwori tHh Fth [e8C]. aTrhdeioreMfoErMe, So™nlysy msteinmori nchealdnegrelys wpaetrie netxspinecttheed,G aelrthmoaunghe  iatl twhacas rae 
psyrestsepmecwifiiethd adimva onfc eodurc hrerognisitcryH tFo,  cuosrer ePlaAtPin gdatthae fcohra fnugrethseorf ignudiidveidlinuea-lr uecpotimtrmateionnd eodf HF 
medication.d   oses during 12 months of follow-up with PAP changes. Our analysis has two
mainSreecsounltds:, Faisr set,xiptedcetmedo,n  tshtrea taevsetrhaagten odsoisgangiefi coafn tAcChaEn‐Ig easnidn gAuRidBe ldineec-ldinireedc teodvemr etdimicael, 
wthheerarepaies sA(RGNDIM doTs)ew aenrde fpreoqsusiebnlecyw initchrePaAsePd- gnuoind‐esdignmifoincaitnotrliyn. gThinis aisd dvaune cteod theel dseterplywHisFe 
ipnatteigenratstioalnr eoafd AyRreNcIe isvinincge c2l0in16ic,a wllyhiocpht iism wiziethdinH tFh-me oebdsicearvtiaotnio. nA tcicmored oinf gthteo pthresiennctl uasniaoln‐
ycrsiitse. rIian oaf poruervrieoguissltyry p, iunbclilsohseeda srseopcoiartti onf twhiet hMthEeMCSH‐HAFM trPiIaOl, NAtRrNialI [u2s3e], wthaesP aAsPsosceiantseodr 
with less use of loop‐diuretics compared to non‐ARNI use at baseline [25]. In addition, 
 
Life 2022, 12, 766 9 of 12
system has been implanted into patients who already received drug and device treatments
for HF [8]. Therefore, only minor changes were expected, although it was a prespecified
aim of our registry to use PAP data for further individual uptitration of HF medication.
Second, as expected, the average dosage of ACE-I and ARB declined over time,
whereas ARNI dose and frequency increased non-significantly. This is due to the stepwise
integration of ARNI since 2016, which is within the observation time of the present analysis.
In a previously published report of the MEMS-HF trial, ARNI use was associated with
less use of loop-diuretics compared to non-ARNI use at baseline [25]. In addition, during
9 months of follow-up, the loop diuretic dose increased to a non-significant, smaller extent
in ARNI users compared to non-ARNI users [25]. In our single center cohort, loop diuretic
dose was not significantly different between ARNI users and non-ARNI users, although the
5 patients who were either switched to ARNI or received ARNI dose increases demonstrated
a decline in the loop diuretic dose, in addition to a decrease in PAP. Interestingly, the dose
increases for other HF medications, such as ACE-I/ARB, beta blockers, or MRAs, did not
show a uniform response for diuretic dose or PAP.
With respect to other HF medication, only 50% of the recommended dose of MRA
could be achieved in 16 HF patients, whereas 2 patients could not even tolerate an MRA.
In 16 patients, a non-significant increase in MRA dose could be detected from baseline to
6 months, but this was followed by a subsequent decline until 12 months of follow-up due
to recurrent hyperkalemia episodes. Currently, one would expect that improved results
with a higher percentage of MRA treatment and doses can be expected, because SGLT2
inhibitors reduce the risk of MRA-associated hyperkaliemia [26], and novel potassium
binders like patiromer and sodium zirconium cyclosilicate are now available [27,28] and
are recommended in the ESC 2021 HF guidelines [6].
Most medication changes occurred within the first 3 months, and the frequency of
changes decreased during 12 months of follow-up. This is in line with previous studies
(CHAMPION and MEMS-HF) [21,25], which both showed that the treatment modifications
occur with a great intensity right after PAP sensor implantation. However, the absolute
number of medication changes per patient at 3 months was approximately 5.5 in CHAM-
PION (treatment group) and 3.2 in MEMS-HF, compared to 14.5 changes per patient within
the first 3 months in the present cohort, which declined to 5.1 changes per patient over the
following 3 months. This difference may be because the present patients were older and
presented with slightly higher PAP and PVR at baseline, which may reflect more advanced
disease. These efforts to optimize PAP with medication modification demonstrate the
workload associated with hemodynamic-guided HF care in advanced elderly patients,
which is critical for the estimation of HF nurse capacity within a telemedical center [29].
The drug class of SGLT-2-inhibitors were not included as antidiabetic nor HF ther-
apy because patients were included into the registry in parallel to the publication of the
EMPA-REG-OUTCOME trial [30] and prior to the updated guideline recommendation
for antidiabetic treatment, 2018 [31]. More recently, the EMBRACE-HF randomized trial
demonstrated that, in HFrEF patients with an implanted PA pressure sensor, Empagliflozin
was associated with rapid reductions in PA pressures that were amplified over time and
appeared to be independent of loop diuretic management [32]. However, this was not
associated with improved quality of life.
Finally, our results show that a significant reduction in PAP values could be achieved,
despite the fact that we could not increase evidence-based HF medication in individually
optimized NYHA class III elderly HF patients. The reduction in PAP was not directly
correlated with diuretic or other medication dosage, suggesting that the decline in PAP
values may be due to better adherence to HF care.
5. Limitations
The present single center registry comprises only 24 patients with hemodynamic
telemonitoring, with analyses of the changes of evidence-based HF medication during
the 12 months of follow-up. The limited patient number is most likely responsible for
Life 2022, 12, 766 10 of 12
our inability to identify a clear patient profile associated with a positive response to
hemodynamic-guided heart failure therapy. However, the study represents a careful
individual analysis of advanced HF patients being treated in a university outpatient setting.
Author Contributions: Conceptualization, B.A.; methodology, B.A.; software, GraphPad Prism
software (version 9.0) for MS Windows (GraphPad Software, San Diego, CA, USA); formal analysis,
B.R.; investigation, S.F., B.A., E.J.H. and N.E.; resources, LOEWE Center for Cell and Therapy
Frankfurt funded by Hessisches Ministerium für Wissenschaft und Kunst, funding reference number
III L 4-518/17.004 (2010) and the Deutsche Forschungsgemeinschaft DFG SFB 1213, Project B09;
data curation, B.A., E.J.H. and N.E.; writing—original draft preparation, E.J.H.; writing—review and
editing, B.A. and E.J.H.; visualization, B.A.; supervision, B.A. and C.W.H.; project administration, B.A.;
funding acquisition, B.A. All authors have read and agreed to the published version of the manuscript.
Funding: The study was supported by LOEWE Center for Cell and Gene Therapy Frankfurt funded
by Hessisches Ministerium für Wissenschaft und Kunst, funding reference number III L 4-518/17.004
(2010): 50.000 € Deutsche Forschungsgemeinschaft DFG SFB 1213, Project B09: 5.000€.
Institutional Review Board Statement: The study was conducted according to the guidelines of the
Declaration of Helsinki, and approved by the Ethics Committee of Goethe University, Frankfurt,
Germany, (protocol number 253/16; 22 June 2016).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study. Written informed consent has been obtained from the patients to publish this paper.
Data Availability Statement: The data are combined together and analyzed within the single center
registry (NCT03020043) and can be obtained by written request.
Acknowledgments: We thank Kathleen Mantzsch and Meaza Tekeste, as well as the catheterization
laboratory team, for excellent study support.
Conflicts of Interest: B.A. reports having received consulting fees and an unrestricted research
grant from St. Jude Medical, now Abbott, and lecture fees from Abbott, AstraZeneca, Bayer,
BoehringerIngelheim, Chronolife, Medtronic, Novartis, Pfizer, and Vifor.
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