THE RENAL AND METABOLIC MORPHO-FUNCTIONAL

PROFILE OF PATIENTS WITH ACUTE MIOCARDIAL

INFARCTION REVASCULARIZED BY PRIMARY

PERCUTANEOUS CORONARY ANGIOPLASTY

PHD THESIS SUMMARY

SCIENTIFIC COORDINATOR:

Prof. Dr. COVIC Adrian

PHD STUDENT:

BURLACU Alexandru

2017

i

CONTENTS

ABBREVIATIONS iii

GENERAL PART

CHAPTER 1. CHRONIC KIDNEY DISEASE 1

1.1. Definitions and classifications 1

1.2. Risk factors for chronic kidney disease 4

1.3. Modalities of evaluation of renal function 5

1.4. Chronic advanced kidney disease – “end-stage renal disease” 6

CHAPTER 2. ATHEROSCLEROTIC CORONARY ARTERY DISEASE 8

2.1. Generalities and classifications 8

2.2. Coronary atherosclerosis - localization of a systemic pathology 10

2.3. Heart Team Concept 12

2.4. Acute ST segment elevation myocardial infarction 13

2.4.1. Definition and prognosis in the short / long term 13

2.4.2. Treatment algorithms - the role of primary percutaneous coronary

intervention (PCI) 14

2.4.3. Current state of STEMI management in Romania - National Program

of Invasive Treatment of Acute Myocardial Infarction 15

CHAPTER 3. INTERRELATIONSHIPS – RENAL DYSFUNCTION AND

CORONARY ARTERY DISEASE 17

3.1. Cardio-renal syndromes - definitions and classifications 17

3.2. Chronic kidney disease - a cardiovascular risk factor 18

3.3. Atherosclerotic coronary artery disease - an independent risk factor for the

decline in renal function 21

CHAPTER 4. ACUTE KIDNEY INJURY – CONTRAST MEDIA INDUCED

22

4.1. Definitions, generalities and classifications 22

4.2. Epidemiology and pathophysiological mechanisms 24

4.3. Complications of acute kidney injury 25

4.4. Acute renal failure in patients with acute coronary syndrome 26

CHAPTER 5. RENAL ARTERY STENOSIS 27

5.1. Definition and classification 27

5.2. Consequences of renal artery stenosis 27

5.3. Established methods and modern diagnostic methods 29

5.4. Controversy regarding the treatment of renal artery stenosis 31

5.5. Pathogenic features: risk groups and screening 34

CHAPTER 6. ARTERIAL STIFFNESS 36

6.1. General and surrogate markers 36

ii

6.2. Dynamics of structural and functional modifications of the stiffened

arterial wall 36

6.3. Clinical implications and influence of vascular stiffness on cardiovascular

prognosis 38

6.4. Therapeutic features 39

CHAPTER 7. MULTI-SITE ATEROSCLEROTIC ARTERIAL DISEASE 41

7.1. Definition and utility 41

7.2. Prognostic and screening in different clinical scenarios 42

7.3. Coronary atherosclerosis and other peripheral determinations (carotid,

renal or lower limbs) - management problems 43

PERSONAL PART

CHAPTER 8. MOTIVATION, GENERAL OBJECTIVES AND STRUCTURE

OF DOCTORAL RESEARCH 45

CHAPTER 9. RENAL ARTERY STENOSIS IN STEMI PATIENTS INCLUDED

IN NATIONAL PRIMARY PERCUTANEOUS REVASCULARIZATION

PROGRAM: PREVALENCE AND CORRELATIONS 48

9.1. Introduction 48

9.2. Matherial and methods 49

9.2.1. The research protocol, the investigated population and the location of

the study 49

9.2.2. Ethical considerations 50

9.2.3. REN-ACS registry 51

9.2.4. Angiographic evaluation of renal and coronary arteries 56

9.2.5. Biological analyzes and cardiac ultrasound 64

9.2.6. Analysis of body composition 65

9.2.7. Measurements for the evaluation of arterial stiffness 66

9.2.8. Statistic analysis 68

9.2.9. CRUSADE score - method of assessing haemorrhagic risk 69

9.3. Results 69

9.3.1. Baseline features 69

9.3.2. Comparative view on patient group RAS + versus patient group RAS-

79

9.4. Discussions 85

9.4.1. Discussions on the general results of the REN-ACS registry 85

9.4.2. Discussions on RAS in REN-ACS 87

9.4.3. Discussions on ischemic and haemorrhagic risks in CKD and ACS

patients: a critical analysis of the Guidelines of the European Society of Cardiology

92

9.5. Conclusions 110

iii

CHAPTER 10. SYNTAX AND CLINICAL SYNTAX SCORES IN ACUTE

MIOCARDIAL INFARCTION PATIENTS WITH PRIMARY PCI:

CORRELATIONS AND PREDICTION OF RENAL ARTERY STENOSIS 111

10.1. Introduction 111

10.2. Materials and Methods 114

10.2.1. Study population, inclusion criteria and measurements 114

10.2.2. Stents types 114

10.2.3. SYNTAX score: calculation method 117

10.2.4. SYNTAX derived scores 126

10.2.5. Clinical SYNTAX score computation 127

10.2.6. Statistical analysis 128

10.3. Results 129

10.3.1. Descriptive statistics by SYNTAX score 130

10.3.2. Descriptive statistics by Clinical SYNTAX score 134

10.3.3. Correlative analyzes for the SYNTAX score and Clinical SYNTAX

score 137

10.3.4. Clinical SYNTAX score vs. SYNTAX score – as RAS + predictors

138

10.4. Discussions 139

10.5. Conclusions 141

CHAPTER 11. MAIN CONCLUSIONS 142

CHAPTER 12. ORIGINALITY AND PERSPECTIVES OF THESIS 143

REFERENCES 144

ANNEXES 168

Anex 1: Informed consent 168

The PhD thesis includes:

• The General part consists of 7 chapters totaling 45 pages

• The Personal part consists of 5 chapters totaling 100 pages

• Bibliographic references containing 448 bibliographical references

• Attachment section

• Iconography consisting of 77 tables and 66 figures

• List of articles published during the doctoral program: 3 ISI articles as first

author and 1 ISI article as second author.

The abstract selectively reproduces the iconography and bibliography in the text,

observing the numbering and the content of the thesis in extenso. The present

bibliographic references are identical to those existing in the PhD thesis.

Keywords, MeSH list: coronary artery disease, chronic kidney disease, renal artery

stenosis, acute miocardial infarction, SYNTAX score, arterial stiffness, dehidration,

prediction models, Guidelines, bleeding risk, thrombotic risk.

1

MOTIVATION, GENERAL OBJECTIVES AND STRUCTURE

OF DOCTORAL RESEARCH

Our doctoral research mainly focuses on a complex analysis of

kidney-to-heart inter-relationships on several levels (kidney: structure,

function, renal artery, coronary epicardial arteries, myocardial systolic

function) in a particular clinical-metabolic context with acute myocardial

infarction, assessment of vascular rigidity, hydration composition)

(Figure 8.1).

The reasons why some study protocols have been developed and

numerous resources have been invested stem from the fundamental

premise that the number of patients with acute myocardial infarction or

with chronic kidney disease or both is extremely high. Both pathologies

frequently coexist and are generating numerous cardiovascular and renal

terminal complications, with extremely high morbidity and mortality.

To date, an increased volume of clinical trials and a very large

scientific community involved in the above mentioned pathology show

the major interest in both diseases and the financial resources invested

(both in research and in the implementation of new medications and

protocols). Newer measures and more effective protocols can simplify

the identification of those complex patients for whom complex and

expensive therapeutic resources are already invested. For example,

simple prediction of RAS presence in AMI patients may lead to the

development of screening protocols at the same time as the acute

coronary procedure.

In the argumentation of the doctoral motivation we took into

account that:

over 30% of patients with acute myocardial infarction have a chronic

renal dysfunction;

Chronic renal impairment influences the progression and short-term

prognosis of STEMI patients as well as the recurrence of coronary

events by one year;

medication given to patients with acute myocardial infarction is

sensitive (remittance) to renal function, and the latter is often severely

affected by AMI management (eg concomitant use may severely

2

aggravate renal dysfunction or the administration of inhibitors of

angiotensin converting enzyme may increase the degree of pre-

existing renal dysfunction);

the main cause of mortality in kidney patients is cardiovascular (of

which myocardial infarction is an important percentage);

the percentage of RAS in patients with CAD (non-acute) is important

(one in five chronic CAD patients also has significant RAS;

the RAS prevalence is still unknown in patients with AMI;

RAS predictors in patients with AMI are not evaluated in order to

develop a screening protocol simultaneously with the

coronarography time;

these patients with ACS have no morpho-functional characterization

of the kidney (kidney arteries, kidney size, glomerular filtration rate);

there is no data on the metabolic profile of patients with AMI and

RAS (serum lipids, glycemia);

no vascular rigidity measurements were performed in patients with

renal and coronary multi-site atherosclerotic lesions (especially in

patients with acute coronary syndromes);

there is no hydration status data in coronary patients (in acute

myocardial infarction) with or without RAS;

there are no data on the usefulness and correlations between

complexity scores of coronary lesions (SYNTAX, Clinical

SYNTAX) and other peripheral determinations (RAS);

there is no uniform assessment of hemorrhagic and ischemic risk in

ACS in renal patients;

management recommendations (stratification of ischemic and

hemorrhagic risk) in ESC guidelines in renal patients suffering from

acute coronary events are scattered and often devoid of evidence;

there are numerous "sensitive areas" in the context of ESC treatment

guidelines for patients with advanced CKD and coronary artery

disease (because randomized trials have excluded patients with renal

dysfunction in principle).

Our doctoral research aims to investigate and clarify the above-

mentioned aspects by going on three intersecting directions (Figure 8.2):

3

1. A prospective non-randomized unicentric study, in which:

we enrolled a group of consecutive patients with acute myocardial

infarction;

we evaluated the presence of renal artery stenosis by renal

angiography simultaneously with the cardiac catheterization

procedure;

we have set up a register based on the European CARDS standards;

we have entered data on enrolled patients (demographics, co-

morbidities, blood tests, echocardiographic parameters);

we measured and recorded vascular rigidity parameters;

we measured and recorded hydric status and body composition by

bioimpedance;

we subsequently analyzed correlations between the presence of RAS

and the other characteristics of patients with AMI;

we have developed a multivariate RAS prediction model based on

previously identified variables;

we followed the development of a screening protocol based on the

results of the prediction models.

2. A post-hoc analysis of the population enrolled in the first study, in

which:

we stratified the patients included in the registry according to

SYNTAX and Clinical SYNTAX coronary complexity scores;

we analyzed the registry in order to identify the variables correlated

with the two scores;

we evaluated the predictive potential of the two scores for RAS.

3. A literature review of hemorrhagic and ischemic risks, in which:

we have identified the clinical, therapeutic and prognostic features of

patients with acute coronary syndromes and CKD;

we analyzed the guidelines in the latest ESC guides on the

management of these patients;

we identified and evaluated the main "sensitive areas" existing in

these Guidelines;

4

we suggested possible directions in the management of renal patients

with ACS.

Figure 8.1. Main approaches in doctoral research.

5

Figure 8.2. Directions in doctoral research.

6

RENAL ARTERY STENOSIS IN STEMI PATIENTS INCLUDED

IN NATIONAL PRIMARY PERCUTANEOUS

REVASCULARIZATION PROGRAM: PREVALENCE AND

CORRELATIONS

Materials and Methods

In our cohort, prospective, randomized, non-randomized (REN-

ACS) study, 250 consecutive patients with ST segment elevation acute

myocardial infarction were enrolled who were eligible for inclusion in

the National Percutaneous Treatment Program of Acute Myocardial

Infarction.

Of the 250 consecutive patients referred to primary angioplasty,

37 subjects were excluded from the study, with only 213 patients

performing coronary angiography and renal angiography. Subsequently,

a total of 181 people met the full inclusion criteria (32 patients were

excluded for incomplete data reasons).

This study was conducted between October 2014 and March 2015

at the "Prof. Dr. G.I.M. Georgescu "- Iaşi.

The research protocol was registered with NCT02388139 on

ClinicalTrials.gov, the most well-known American institution supported

by the National Library of Medicine (NLM) and the National Institutes

of Health (NIH).

All patients were admitted for percutaneous emergency coronary

intervention (through the National Percutaneous Treatment Program of

Acute Myocardial Infarction) and were treated (medically and

interventionally) in accordance with standard European protocols (1).

Coronary angiography was performed by a major arterial femoral

approach less than 12 hours after the onset of angina pectoris in AMI.

The detailed coronarographic aspect (by segments), the type of implanted

stent, the specific periprocedural complications, the TIMI flow at the end

(Figure 9.2) were noted.

Concomitantly, renal diagnostic angiography was performed in

the same procedure. Independent measurements were made by two

operators based on a predefined scale, measuring the size of the kidneys

(after the records during the procedure).

7

Laboratory blood tests (standard set - blood count, biochemistry,

lipid profile) were recorded and noted in the database.

Based on the clinical examination and the interview defined

previously (2) (adapted to the European CARDS data recording

standards), information was obtained on:

medical history - data relevant to coronary artery disease and

RASc - previous interventions, chronic kidney disease, chronic

heart failure, peripheral arterial disease;

cardiovascular risk factors - age, weight, height, abdominal

perimeter, body mass index, smoking, sedentary disease, diabetes

mellitus, hypertension, dyslipidemia;

Killip-Forrester classification of post-infarct cardiac

insufficiency;

According to the management protocol of patients with AMI,

cardiac ultrasound was performed before angiography (measurement and

recording of the left ventricular ejection fraction) immediately after the

patient's admission to the Coronary Intensive Care Unit.

Twenty-four hours after percutaneous intervention the parameters

derived from electrical bioimpedance and arterial stiffness were

evaluated and recorded.

The Research Ethics Committee of the University of Medicine

and Pharmacy "Gr. T. Popa "University of Iasi approved the study

protocol. This protocol was based on international ethical principles of

scientific research, to which Romania also joined (3). All patients were

invited to sign an informed consent (approved by the Ethics Commission

- Annex 1).

To perform body composition analysis, we used Portable Body

Composition Monitoring (BCM®, Fresenius Medical Care, Germany).

The results were recorded in two minutes on a dedicated card and then

transferred to our REN-ACS database through the Fluid Management

Tool® software.

We used the SphygmoCor® device (AtCor, Australia) to acquire

carotid-femoral and carotid-radial PWV and aortic augmentation index.

8

Figure 9.2. Flow-chart in REN-ACS

Results

Renal atherosclerotic lesions (both significant and insignificant)

were found in 81 patients (45% of the total): 59 of them had unilateral

determinations (representing 32.6%) and 22 patients showed bilateral

injuries (equivalent to 12.2%) (Figure 9.17). The distribution of patients

in the batch according to eGFR at admission is shown in Figure 9.21.

9

Figure 9.17. Renal atherosclerotic damage

Figure 9.21. Number of patients with STEMI stratified after renal function at

presentation (total group of 181 patients).

The mean CRUSADE score for estimating hemorrhagic risk in

the infarction was 25.9 ± 11.7 standard deviation. Table 9.13 shows that

the mean CRUSADE score in bi- or tri-coronary patients is significantly

higher than in single-coronary patients. Similarly, by dividing the GFR

100; 55%

51; 28%

18; 10%

12; 7%

30; 17%

Afectarea aterosclerotică artere renale

Fără Leziuni fără semnificație SAR+ Bărbați SAR+ Femei

60 95 23 1 20

20

40

60

80

100

Funcție normală

BRC 2 BRC 3 BRC 4 BRC 5

RFG (după CKD-Epi)

10

on the two subgroups mentioned, there is a strong statistical significance

of decreased renal function in multi-coronaries.

Table 9.13. Distribution of the CRUSADE hemorrhagic risk score depending

on the number of affected coronary arteries.

Total group

(n=181)

Unicoronary

(n=79)

Bi- or tri-

coronary

(n=102)

P value

CRUSADE

score

25,9 ± 11,7 23,8 ± 10,6 27,5 ± 12,2 0,03

eGFR 79,5 ± 20,0 84,8 ± 18,2 75,4 ± 20,5 0,001

Table 9.16 describes PWV-cf and PWV-cr averages based on the

number of coronary arteries involved. It is noted that in the multi-

coronary patients, the carotid-femoral pulse wave velocity is significantly

higher than in the unicoronary patients.

Table 9.16. Pulse wave velocities (carotid-femoral and carotid-radial) in

unicoronarian and multi-coronary patients.

Total group

(n=181)

Unicoronary

(n=79)

Bi- or tri- coronary

(n=102) P

PWV-cf 9,39 ± 2,54 8,94 ± 2,0 9,73 ± 2,8 0,04

PWV-cr 7,00 ± 1,15 7,1 ± 1,1 6,93 ± 1,2 0,41

Results of body composition records by BCM depending on the

presence or absence of CKD (GFR less than 90 mL / min / m2). It is noted

that TBW, ECW and ICW values are significantly lower (dehydration)

in patients with renal dysfunction than those with normal renal function.

RAS + (defined as significant stenosis - over 50% - renal artery)

was identified in 30 patients, representing 16.6% of the study group.

The univariate logistic regression analysis evaluated the

association of each of the variables with the presence of RAS + (Table

9.28).

In multivariate models, variables that remained independently

associated with RAS+ were the antecedents of PCI, GFR, multivascular

BCI, TBW or ECW (Table 9.29 and 9.30).

11

Table 9.28. Univariate RAS+ associations.

Parameters Odds Ratio 95% CI

Sex

(1=Male, 2=Female) 2,294 1,006-5,231

Age, yrs 1,039 1,003-1,078

PCI (0=Nu, 1=Da) 11,462 1,996-65,808

CAD (0=Nu, 1=Da) 2,404 1,008-5,731

GFR 0,971 0,952-0,989

Fibrinogen 1,003 1,000-1,005

No of diseased vessels

(0=1 vas, 1=≥2 vase) 3,374 1,448-9,678

PWV-cf 1,202 1,039-1,391

TBW 0,915 0,861-0,973

ECW 0,822 0,703-0,961

ICW 0,882 0,805-0,966

Table 9.29. Multivariate associations of RAS (model with TBW).

Parameters Odds Ratio 95% CI

PCI (0=Nu, 1=Da) 8,590 1,319-55,928

GFR 0,978 0,958-0,999

Number of diseased vessels

(0 = 1 vas, 1 = ≥2 vase) 3,113 1,127-8,593

TBW 0,933 0,875-0,995

Table 9.30. Multivariate associations of RAS (model with ECW).

Parametri Odds Ratio 95% CI

PCI (0=Nu, 1=Da) 8,097 1,178-55,646

GFR 0,974 0,954-0,995

No of diseased vessels

(0 = 1 vas, 1 = ≥2 vase) 3,143 1,143-8,646

ECW 0,845 0,716-0,997

Both models showed accuracy (84.5%), specificity (98.7%),

sensitivity (13.3%), and identical positive (66.7%) and negative (83.4%)

predictive values.

12

Discussions

In the literature, only a few trials and a single systematic review

(4) discussing the incidence of RAS in stable coronary artery disease,

while there is no study evaluating a cohort of patients with AMI. In fact,

all previous studies excluded this category of patients. The systematic

evaluation of existing literature has identified eight studies in which renal

screening angiography was performed in patients with stable coronary

artery disease in elective settings.

Our results show consistent values for the prevalence of RAS in

AMI (16.6%) than those reported for recognized risk groups (suspicion

of renovascular hypertension (4, 5) - 14.1%, hypertension and diabetes

mellitus (6) – 17,1%, chronic coronary disease (4, 7, 8) – 9,1% to 10,8%).

Our doctoral research is the first published trial evaluating the

arterial stiffness (via PWV) and the hydric status (via BCM) in

consecutive AMI patients.

Our results suggest that increased blood rigidity is associated with

an increased prevalence of RAS in the AMI patients group. We believe

that in-depth research is needed to refine the predictive power of the

interactive relationship between increased arterial stiffness and the RAS

+ phenotype.

One of the strongest predictors of RAS + in our study was the

decline in renal function. Patients in the RAS + trial group had a

significantly lower glomerular filtration rate than those in the RAS-

group, reflecting a more severe and wider coronary disease(9) (9),

correlating with a higher risk of major cardiac events even after an AMI

(10). The decrease in glomerular filtration rate may be due to the

development of RAS, namely chronic ischemic nephropathy following

atheromatous stenosis and / or the coexistence of multiple risk factors.

Furthermore, the CRUSADE score was significantly higher in the

RAS + study group. This means that patients with STEMI and RAS +

have a significantly higher risk of bleeding than patients without RAS.

thus leading to even greater risk of major cardiac events (11).

The present PhD research is the first to suggest the importance of

bioimpedance and water status assessment in conjunction with RAS

13

coexistence in AMI patients by using a more objective measurement

procedure (12) and reproducible (13).

Following the steps (initially we performed the univariate

analysis) and the results obtained from our statistical analysis

(multivariate analysis), we recommend a screening algorithm consisting

of performing renal angiography concurrently with the primary

percutaneous revascularization intervention in specific patient groups

with AMI, which presents a history of percutaneous revascularization

interventions, multivascular coronary disease, low glomerular filtration

rate and high dehydration. The predictive multivariate model has a good

specificity and low sensitivity, and the evaluation technique for RAS

diagnosis is simple and non-aggressive.

Figure 9.32. Predictive multivariate model proposed (following REN-ACS statistical

analysis).

Current therapies are confronted with uncertainties about dosage

and safety over long-term benefits. There is divergent information on the

outcome of the intervention procedures. Generally, patients with CKD

remain poorly represented in major clinical trials, and when included,

they are often inadequately investigated. The guidelines do not currently

recommend the implementation of simple and cost-effective measures

RAS în STEMI

APP PCI

RFG ↓

TBW / ECW ↓

Multi-coronarieni

14

that could be protective measures for these patients, such as creatinine

clearance clearance or eGFR recommendations.

We believe that the lack of clinical trials must not discourage the

common sense of clinical practice, and that clearer decision-making

algorithms with better ends are feasible and necessary. Furthermore, in

our opinion urgent randomized robust studies are urgently needed to

explore and cover the large gaps in the information framework covering

this patient population. They also require specific assessment procedures,

and we believe that it is imperative to design a strategy with specific

measures translated by effectively reducing the incidence of

haemorrhages.

SYNTAX AND CLINICAL SYNTAX SCORES IN ACUTE

MIOCARDIAL INFARCTION PATIENTS WITH PRIMARY PCI:

CORRELATIONS AND PREDICTION OF RENAL ARTERY

STENOSIS

Materials and Methods

The research group of this post-hoc registry analysis is part of the

previous REN-ACS study.

The SYNTAX score (SS) is a tool for calculating the severity of

coronary atherosclerotic disease. It's based on a complex computational

algorithm that uses 11 elements of severity (14). Currently, the

calculation is done online at www.syntaxscore.com. If the initial score

was developed for patients with left coronary artery lesion or severe

tricoronary lesions to guide the revascularization method (between

percutaneous coronary angioplasty and aortic coronary bypass surgery),

further studies have shown that it can be used as a predictor of major

cardiovascular events and in the acute context (acute coronary

syndromes) or in patients with single or bi-coronary lesions.

The SYNTAX Clinical Score was calculated retrospectively for

each patient in the REN-ACS after the SS calculation (described in

CHAPTER 10.2.3). The formula used was CSS = [SS] × [modified

ACEF score] (15).

Results

15

The calculations behind the current analysis were based on SS

and CSS assessments. Thus, SYNTAX scores varied between 1 and 46.5

with a mean ± standard offset of 16.95 ± 8.45 and a median of 17.5.

Clinical SYNTAX scores were in the range of 1.22 and 255.15 with a

mean ± standard offset of 39.3 ± 41.3 and a median of 28.

The study group was divided by SS into tertiles as follows: tertile

1 SS ≤ 11 (n = 59). Tertile 2 SS 11.1 = 19.9 (n = 61 patients), tertile 3 SS

≥ 20 (n = 61). After the descriptive and correlative analysis of SS, the

patient group was divided by tertiles CSS: tertile 1 CSS ≤ 19.2 (n = 60

patients), tertile 2 CSS 19.3 - 38.8 (n = 61 patients) and tertile 3 CSS ≥

38.9 (n = 60 patients).

The results of coronary angiography and renal angiography are

shown in Table 10.11. Both multi-coronary patients and those with RAS

+ are significantly more numerous in the upper tertile of the SS.

Table 10.11. Results of coronary angiography and renal angiography after the SS.

Variabile

Tertile 1

SS ≤ 11

(n = 59)

Tertile 2

SS 11,1–

19,9 (n =

61)

Tertile 3

SS ≥ 20

(n = 61)

p1

(I–II)

p2

(II-

III)

p3

(I-III)

Bi- or tri-

coronary, n (%)

15 (25,4) 40 (65,5) 47 (77) 0,001 0,16 0,001

RAS+, n (%) 5 (8,5) 8 (13,1) 17 (27,8) 0,41 0,043 0,006

The stratification of renal angiography results after CSS (Figure

10.22) showed that the prevalence of RAS + was higher in the upper

third.

The SS-related independent variables were: FEVS <40%, RAS +,

ICC history and multivascular BCI (Table 10.20).

16

Figure 10.22. RAS by CSS tertiles (p 1 = 0.77, p 2 = 0.003 and p 3 = 0.001).

Similarly, CSS-related independent variables in the multivariate

linear regression analysis were: RAS +, PWV-cf, BCI history,

multivascular CAD, total serum cholesterol and TBW (by ICW, but not

ECW) (Table 10.21).

Table 10.20. Independent variables associated with SS in multivariate analysis.

Variable B value CI 95% P Value

RAS+ 3,31 0,40 – 6,23 0,026

CHD 3,53 0,80 – 6,27 0,012

LVEF lower 40% 3,33 1,2 – 5,46 0,002

Multivessel 6,21 3,99 – 8,42 0,001

Table 10.21. Independent variables associated with CSS in multivariate analysis.

Variable B value CI 95% P value

RAS+ 26,46 12,43 – 40,48 0,001

CAD 17,69 6,48 – 28,9 0,002

Multivessel 16,75 6,45 – 27,04 0,002

PWV – cf 3,18 1,14 – 5,21 0,002

TBW -0,81 -1,46 – -0,153 0,016

Total colesterol -0,12 -0,22 – -0,018 0,022

5 619

0%

20%

40%

60%

80%

100%

Terțila I a CSS Terțila II a CSS Terțila III a CSS

Stenoza de arteră renală

SAR+ Fără SAR

17

We performed the ROC curves (and AUC for each) for both SS

and CSS. The objective was to evaluate the predictive accuracy of the

two RAS + scores. Both curves are shown in Figure 10.23. The area

under the curve for SS was 0.69 (CI 95% 0.58 - 0.79) and for CSS was

0.74 (CI 95% 0.63 - 0.84) (p <0, 05 for both analyzes, DeLong method).

Figura 10.23. Comparația între AUC pentru ROC SS și CSS.

Discussions

Our approach is the first investigation to calculate and compare

SS and CSS in consecutive STEMI patients for pPCI. Moreover, the two

scores were first evaluated as RAS + predictors (at least until now, the

scores were only used for the assessment of cardiovascular prognosis).

Another novelty of the present study is that PWV and post-procedural

body bioimpedance (BCM) parameters are now analyzed in correlation

with the two SS and CSS scores.

Thus, we can clearly state that patients with RAS + have an

increased SYNTAX score, or in other words, a high SS score correlates

with multi-site atherosclerosis. This information is extremely useful (to

18

configure the risk prediction profile) and is available early to prevent

renal impairment in association with the presence of RAS (especially in

the context of the use of iECA with diuretics or dehydrated patients).

Concretely, if a STEMI patient is also computed with the

SYNTAX score after coronarography, anginal angiography of the renal

arteries (where the SS is very high) can also be considered. Moreover, at

least theoretically, one may consider a plan for early revascularization of

RAS (immediately after solving the coronary vasculitis).

Although this idea may seem utopian, there is evidence to suggest

that performing renal angioplasty at the same time as pPCI provides long-

term benefits (decreases mortality rates and cardiovascular events) (16).

Our study identified a close correlation between CSS score and

extensive atherosclerosis (RAS +, BCI history and multicoronary

disease), increased arterial stiffness (by PWV cf) and dehydration (low

TBW by ICW but not ECW) and low total cholesterol 10.24).

Figure 10.24. The independent variables correlated with SS and CSS respectively in

multivariate regression analysis.

This interesting observation suggests for the first time in literature

that an increased CSS score is associated with the presence of RAS,

increased vascular stiffness and dehydration.

If we look at the screening for RAS, negative interpretation of

low CSS values (under 44) can ensure that a patient does not have renal

SS

Bi/tri coronarieni

ICC clinică

RAS+

FEVS sub 40%

CSS

ATS extensiva

Colesterol total

Rigiditate arterială

Deshidratare

19

artery stenosis (negative predictive value is 92%). Moreover, CSS below

the threshold value can identify 85% of those who do not have RAS +.

On the other hand, the modest results in confirmation of the disease

(positive predictive value of 43%) impose the need for additional

investigations and tests. Therefore, developing a better predictor,

possibly by incorporating a bio-marker (17, 18) into the CSS, can

increase the sensitivity of the score from 60% to 80%, in addition to

preserving the current very good specificity (85%).

If, five to ten years ago, the indication of implantation of

pharmacologically active stents was reserved only for elective cases and

diabetic patients with small vessels or long lesions, the recommendation

in the ESC Guidelines is now the first intention of DES in infarction.

Only in non-compliant patients with contraindications of prolonged dual

agglutination or increased hemorrhagic risk is BMS preferred.

The fact that the distribution of DESs and BMSs in all SS tertiary

is uniform means that their choice was not based on the complexity of

the coronary artery disease (old criteria) but on the new guidelines in the

Guides.

The difference between the CSS score and the SS (insertion of the

clinical variables in addition to the anatomical ones) is also reflected in

the choice of the type of stent. Where CSS is increased (and as we have

seen the CRUSADE score is increased), a simple metallic stent (or

balloon angioplasty) was preferred at the expense of sub-use of DESs.

This observation is consistent with increased hemorrhagic risk and is a

strong argument for adherence to ESC recommendations.

MAIN CONCLUSIONS

Patients with RAS + and acute myocardial infarction have a particular

metabolic, endothelial and hydric profile specific to advanced and

extensive atherosclerosis (multi-site);

Multi-vascular coronary artery disease has been shown to be a strong

predictor for RAS, which is in line with the advancement in most

cases of multi-site arterial disease;

20

For the same reasons, vascular stiffness is more pronounced in

patients with RAS +;

All patients with STEMI were relatively dehydrated (mild subclinical

dehydration), which can be interpreted either as a consequence of the

particular hormonal and metabolic environment in AMI context or as

an independent and unknown risk factor;

Moreover, patients with RAS + and STEMI were significantly

dehydrated than those without RAS, dehydration may have origins

associated with RAS + induced renal dysfunction;

A low GFR in STEMI correlates with the presence of RAS +;

The predictive model of RAS + (which includes the history of PCI,

low GFR, multi-coronary damage and dehydration) has a very good

accuracy and specificity and can be integrated into screening

algorithms;

SYNTAX and Clinical SYNTAX Coronary Complexity scores can

also be used as a predictor of RAS (not only for prognostic

assessment);

Patients with STEMI and CKD have an increased risk of major

bleeding;

Current treatment algorithms include unclear dosages and safety over

long-term benefits. There is divergent information on the outcome of

the intervention procedures (it seems that patients with advanced

CKD have low benefits from PCI in terms of mortality and

complications);

Patients with CKD remain poorly represented in major clinical trials,

and when included, they are often inadequately investigated. The

guidelines do not currently recommend the implementation of simple

and cost-effective measures that could be protective measures for

these patients, such as, for example, obtaining emergency GFR (early

blood tests and updated calculation formulas that would allows early

adjustment of medication and early stratification of ischemic and

haemorrhagic risks);

21

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