UNIVERSITY OF MEDICINE AND PHARMACY “VICTOR BABES” OF TIMISOARA FACULTY OF GENERAL MEDICINE Department of Internal Medicine V Discipline of Medical… [616546]

UNIVERSITY OF MEDICINE AND PHARMACY
“VICTOR BABES” OF TIMISOARA
FACULTY OF GENERAL MEDICINE
Department of Internal Medicine V
Discipline of Medical Semiology
RABIA KHOURY

M.D DEGREE THESIS
Scientific coordinator
Șef de Lucrare Dr. Andor Minodora

ara Timiso
2019

I
UNIVERSITY OF MEDICINE AND PHARMACY
“VICTOR BABES” OF TIMISOARA
FACULTY OF GENERAL MEDICINE
Department of Internal Medicine V
Discipline of Medical Semiology

RABIA KHOURY

M.D DEGREE THESIS
Clinical Changes in Heart Failure with Preserved Ejection
Fraction
Scientific coordinator
Șef de Lucrare Dr. Andor Minodora

Timisoara
2019

II
TABLE OF CONTENTS
GENERAL PART
List of abbrev iation ………………………….. ………………………….. ………………………….. …………….. IV
Acknowledgement ………………………….. ………………………….. ………………………….. ……………….. VI
1. Introduction . ………………………….. ………………………….. ………………………….. ………………………. 7
1.1. Heart Failure ………………………….. ………………………….. ………………………….. …………………… 8
1.2. Epidemiology ………………………….. ………………………….. ………………………….. …………………. 8
1.3. HFrEF vs. HF pEF ………………………….. ………………………….. ………………………….. …………… 9
1.4. Comorbidities and Risk Factors ………………………….. ………………………….. …………………. 10
1.5. Pathophysiology of H FpEF ………………………….. ………………………….. ……………………….. 11
1.5.1 . Diastolic Dysfunction ………………………….. ………………………….. …………………………. 11
1.5.2 . Systolic Dysfunction ………………………….. ………………………….. ………………………….. . 12
1.5.3 . Pulmonary HTN ………………………….. ………………………….. ………………………….. …….. 12
1.5.4 . Cardiovascular Reserve dysfunction ………………………….. ………………………….. …… 13
1.5.5 . Ventricular -arterial coupling ………………………….. ………………………….. ………………. 14
1.6. Clinical Presentation ………………………….. ………………………….. ………………………….. ……… 14
1.6.1 . Signs and Sy mptoms ………………………….. ………………………….. ………………………….. 14
1.6.2 . HF Classifications ………………………….. ………………………….. ………………………….. …. 15
1.6.3 . Diagnosis ………………………….. ………………………….. ………………………….. ………………. 16
1.6.4 . Tests ………………………….. ………………………….. ………………………….. ……………………… 16
1.6.5 Complications ………………………….. ………………………….. ………………………….. ………… 18
1.7. Treatment and Management ………………………….. ………………………….. ………………………. 19
1.7.1 . Non-Pharmacologi cal therapy ………………………….. ………………………….. …………….. 19
1.7.2 . Pharmacological therapy ………………………….. ………………………….. …………………….. 20

III
CHAPTER 2
2. SPECIAL PA RT ………………………….. ………………………….. ………………………….. ……………… 21
2.1. Introduction and Aim of the Study ………………………….. ………………………….. …………….. 21
2.2. Material and Methods ………………………….. ………………………….. ………………………….. ……. 22
2.3. Result s ………………………….. ………………………….. ………………………….. ………………………….. 23
2.4. Discussion ………………………….. ………………………….. ………………………….. …………………….. 43
2.5 Conclusion ………………………….. ………………………….. ………………………….. …………………….. 45
References ………………………….. ………………………….. ………………………….. ………………………….. . 46

IV
ABBREVIATIONS LIST
HR – heart failure
LVEF – left ventricular ejection fraction
HFpEF – heart failure prese rved ejection -fraction
HFrEF – heart failure reduced ejection – fraction
EF – ejection fraction
EDV – end -diastolic volume
ESV – end systolic volume
COPD – chronic obstructive pulmonary disease
HTN – hypertension
AF- atrial fibrillation
ROS – reactive oxyg en species
NO – nitric oxide
CC- cardiac cachexia
PKG – protein kinase G
ECM – extra cellular matrix
MMPs – matrix metalloproteinase
TIMPs – tissue inhibitors of metalloproteinase
SR – sarcoplasmic reticulum
CO – cardiac output
PH – pulmonary hypertensio n
PAP – pulmonary artery pressure
LA – left atrium
HR – heart rate

V
V-A – ventricular arterial
Ea – arterial elastance
Ees – ventricular elastance
BNP – B-type natriuretic peptide
NT-pro BNP – N-terminal pro -B type natriuretic peptide
BBs – beta-blockers
ACE -I – angiotensin covering enzyme
ARBs – angiotensin receptor blockers

VI

ACKNOWLEDGMENT
In this part of my scientific work, I want to take the opportunity and say a few words
about my coordinator Dr. Minodora Andor. Already in the third year, we met the first
time, since she was teaching my colleges and me in medical semiotics. At that time I
had no idea what specialization I am interested in and where I want to work later.
Dr.Minodora Andor explained and teach us not only semiotics but also in ca rdiology.
The passion she had while talking about cardiologic cases made me think about the
direction first. Later in cardiology, it caught me completely and I decided to do my
thesis with cardiac topics since I want to apply for a job in this direction in my country
later too.
Thank you, Dr. Minodora Andor, for your help and pushing me in the right direction.
I would like to take the opportunity also to thank Prof. Dr. Diana Lungea nu honestly for
helping and supporting me with my data analyzing. Prof. Dr. Diana Lungeanu explained
and solved all my questions patiently.

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GENERAL PART
1. INTRODUCTION
Heart failure (HF) is an epidemiological situation, which keeps expanding, including a
leading reason for mor bidity coupled w ith mortality and higher healthcare costs. More
than 5 million patients are facing HF in the USA . (1)
HF prevalence keeps developing and growing as the main cause of progressive elderly
and life prospect prolongation . The majority, above 66 years, female gender frequently
affected by Hf due to hypertension and present more severe symptoms , compared to the
male gender. HF is a highly regarded cause that lead s to hospitalization for old such as
adult persons . (1)
HF is the case, whenever the muscle of the heart is injured and damaged , therefore will
not pump effectively and becomes weak er. After this damage occurs to the heart ’s muscle,
it is could not be recover. There are two diffe rent pathological forms of left -sided HF:
1) Among 50% if the patients that present symptoms/ signs of HF are found to reach
almost a normal left ventricular ejection -fraction (>50%) , which represent a unique
clinical syndrome, generally known as, HF with preserved ejection -fraction (HFpEF) . (2)
2) 50% of the HF pat ients might have a lowering of left ventricular EF ( < 40%), and it is
known as HF with reduced ejection -fraction. (2)
HFpEF comprises a heterogeneous of diseases, which are unified by the existence of
LVEF greater than 50%, confirmation of impaired diastol ic performance commonly with
a rais ed natriuretic -peptide. Despite, HFpEF is continuously starting to become the major
form of HF, disease modifying treatment solutions for the patients keep to be limited and
insignificant . It affected essentially elderly which is the important risk factor, female
gender with highest comorbidities profile. High blood pressure, ischemic coronary
diseases, atrial fibrillation, and diabetes are the most noticed widespread comorbidities in
HFpEF patients. (1)

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1.1. Heart Fail ure
In the most recent obtainable guidelines of European Society of Cardiology, HF was
described as a pathological -condition , in which the heart is too fatigued to generate
enough cardiac output , to supply tissue and organs demands, as consequences of the
functional and structural abnormalities of filling the ventricles and ejection of the blood.
Limited cardiac output and or elevated intra -cardiac pressure during stress or at rest might
occur. (2)(3)
Indications of HF most often lean on the existence of r aised left and/or right -heart
pressure during the filling phase, however , the phrase congestive HF is not ideal used,
since many pat ients do not present congestion . (2) (3)

1.2. Epidemiology of Heart Failure

Globally, 37.7 million patients are suffering from HF, which keeps on increasing
worldwide. Annually, in the US th ere are 650,000 new diagnosed cases . Between 1979
and 2004, the quantities of patients that hospitalized tripled, taking a giant leap from 1.27
to 3.86 million cases. In these days, there are 6 million Americans and 15 million
Europeans living with HF. HF prevalence is proportionally related to aging, patients older
than 65 are the ones mostly affected by this condition . In developed countries, the
prevalence of this condition is about 1%-2% of the adults, and increases to 10% for
patients above 70 years . At any age, HFpEF is widely common in females, compared with
HFrEF, which is more common in males. Clinical trials all over the word shown that the
HFpEF prevalence is higher in the US and Canada in comparison to Western Europe and
Russia . Based on Olmsted county cohort data, which was, collected (1986 -2010), the
HFpEF incidence rate increased from 39% to 56.9%. Hospital readmission rate of patients
with HFpEF is higher than HFrE F, due to the late appearance of symptomatology leading
to late diagnosis and limited treatment options available. (4)

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1.3. Heart failure with reduced vs. preserved ejection fraction
Ejection fraction (EF) referred to the blood amount that ejected out ve ntricles by each
heartbeat proportional to end -diastolic volume. It calculated by dividing the stroke
volume (the difference between EDV and ESV) by end -diastolic volume (end -diastolic
filling) it could be simply determined through echocardiography. (5)
Clinically, EF used to determine the contraction function of the LV and is considered as
a significant prognostic factor. HF patients divided into 3 sub-groups regarding their
LVEF -measurements,
1. HF, reduced ejection -fraction (LVEF<40%),
2. HF, preserved ejection -fraction (LVEF>50%)
3. HF, mid-range ejection -fraction (LVEF 40 -49%).
At any EF abnormality, the similarity of signs/ symptoms in all heart failure patients is
present across the EF range including, neuro -hormonal activation, exercise intoleranc e,
abnormal filling dynamics in LV, diastolic pressure elevation in LV, systolic and diastolic
dysfunction. Currently, HFpEF, as well as, HFrEF are two unique clinical parameters
according to the clear various risk factors, etiologies, and demographic char acteristics.
Patients with HFpEF characterized by 3 main issues (A) age above 65 , (B) female genders
(C) comorbidity, as average there are at least four co -morbidities associated with HFpEF
in each patient, such as obesity, hypertension, COPD, renal insuff iciency. HFrEF , become
related to ischemic heart disease and male gender. HFpEF and HFrEF are new terms that
prioritize more over than "systolic" and "diastolic" heart failure. According to the
researches , that have been done HFrEF, patients may develop di astolic dysfunction.
HFpEF may show marginally reduction of systolic function, and that was improved
through using more sensitive techniques (myocardial strain imaging). (5)

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1.4. Comorbidities and Risk factors of HFpEF
Any existing circumstance that c ontributes to trigger a changing in LV (functionally,
structurally) may lead or progress the risk of forming HF. Notwithstanding that HF
etiologies could vary between HFpEF and HFrEF, there does exist a definite similarity in
etiologies for both HF groups. (6)
Round about 50% of HF patients, represent HFpEF. HFpEF noticed mainly by two
important issues1. Aging 2. Co-morbidities profile.
Hypertension (HTN), elderly and female gender are the most important factors in
patients diagnosed with HFpEF. As per the data obtained from different epidemiological
studies, coronary artery disease exists in 25% -68% of HFpEF patients rendering it a
serious condition in this category. Another major complication it comes along with is the
higher weakening of the LV function leading to an increase in mortality rate. Atrial
fibrillation (AF): the AF presence is elevating with age , and longevity. AF in HFpEF
patients related to LV diastolic and systolic functions, severe neurohumoral response,
activity intolerance and LA hypertr ophy and poor function. HTN, 75% -85% HF patients,
had hypertension earlier in their life. HTN influence inflammation , in turn , it can cause
several structural /functional abnormalities and endothelial dysfunction. (6)
Non-cardiac comorbidities present an i mportant role that cannot be excluded in HFpEF
occurrences such as :
 Obesity
 Diabetes mellitus
 Renal dysfunction
 Sleep apnea
 COPD .
 Systemic inflammatory disease.
Multiple additional factors, which consider as high risk to develop HF, which:
 Post-myoca rdial infarction
 Valvular diseases such regurgitation of aorta and mitral valves
 Cardiomyopathy (hypertrophic, restrictive)

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 Excessive uncontrolled use of medicines such, calcium channel -blockers or beta –
blockers
 Ventricular arrhythmias .
 Pulmonary hypert ension. (6)

1.5. Pathophysiology of HFpEF
1.5.1. Diastolic dysfunction
Diastolic dysfunction is caused by increased stiffness of myocardium and abnormal
relaxation of LV . Extracellular -matrix (ECM) and cardiomyocyte are 2 main
compartments that have a maj or role in diast olic stiffness . The current paradigm suggests
that myocardial remodeling and dysfunction s into HFpEF are a result of the following
events: comor bidities trigger a systemic pro -inflammatory state, which induce s coronary
micro -vascular endoth elial cells to generate reactive oxygen species (ROS). The latter
limit s the bioavailability of NO in turn, gives rise to reduce the action of protein s kinase
G-(PKG) which results i n cardiomyocytes hypertrophy . The consequence s thereof are
concentric LV r emodeling and cardio myocytes stiffening due to hypo phosphorylation of
Titin, which is a highly elastic protein that acts as spring. Stiff cardiomyocytes and
deposition of collagen by myofibroblasts promote diastolic LV dysfunction, the major
deficit in ca rdiac failure in HFpEF [1]. ECM stiffness identified by collagen regulating
and cross -linking of collagen . Collagen type 1 increases in HFpEF, simply by increased
synthesis, and decreased degradation, secondary to down -regulation of MMPs and TIMPs
up-regul ation . MMPs are responsible for decreasing stiffness, when they are
downregulated there is increasing in LV stiffness. This condition could found in
hypertensive and aortic stenosis patients . During diastole, actin -myosin detachments are
related to decrea sed calcium level in cytosol . Phospholamban is phosphorylated through
PKA, which stimul ate calcium reuptake into SR ; parallel with sodium/calcium exchanger ,
as a result , LV relaxation occurs. Decreasing in phospholambans activity , will cause
prolonged actio n potential, therefor diastolic dysfunction occurs. (7)

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1.5.2. Systolic dysfunction
HFpEF was beforehand termed , regarding the old terminology as an "HF with normal
systolic function". Through the use of Tissue Doppler (TDI) , systolic dysfunction and
abnormalities discovered in HFpEF suffers , even with a presence of normal EF. More
specifically, EF measures ventricular -arterial coupling, rather than LV contractility alone.
In normal and hypertensive persons regardless of HF, myocardial contraction raise s,
while EF decreases in patients with HFpEF. In HFpEF, the severity of contractile
dysfunction strongly linked to worse prognosis and elevation in mortality. Disability to
elevate EF due to β -adrenergic stimulation or exercise is associated with passive stiffness,
which in turn affects the contractility and causes abnormality in s ystolic reserve. In
HFpEF, End -systolic elastance (Ees) highly elevated, which consider as the golden
standard way of measuring the contractility of ventricles. Ventricular passi ve stiffness,
concentric hypertrophy increas e influence Ees, therefor Ees affected and increased by
geometrical chamber changes in HFpEF. This elevation in HFpEF indicates that
myocardial contractility at maximal effort. In HFrEF, the systolic abnormality is more
severe than HFpEF, but recent researchers have found that, any minor limitations in
contractility could lead to bad prognosis during exercise stress. Failure to promote
contractility is usually involved with reduced cardiac output (CO) reserves, mo re serious
indications of exercise intolerance appear, as well as a drop in aerobic capacity. (7)(8)

1.5.3. Pulmonary Hypertension
As reported by community -based studies 80% of HFpEF patients present pulmonary
hypertension (PH). PH is high to be relat ed to left -sided heart failure. Which is one of the
most common causes that lead (at rest) to an abnormally increased mean pulmonary artery
pressure (mPAP) greater than 25 mm/Hg, and pulmonary capillary wedge greater or equal
15. Afterload increases in LV, caused by, relaxation Impairment and stiffness of
myocardium. LV with impaired filling becomes noncompliant, which in turn leads to
increase left atrial contraction force , because of increased afterload. In response to this
condition compensatory mechanis m are activated and LA hypertrophy might occur.
Because of retrograde circulatory, pulmonary edema exists. With longer standing, right
ventricular heart failure occurs, due to increased PAP caused by left atrial venous

13
pressure. Currently, PH consider s a common feature of HFpEF. Nowadays , PH consider s
as a therapeutically target in HFpEF patients that develop pulmonary hypertension . (9)

1.5.4. Cardiovascular reserve dysfunction and chronotropic
incompetence
HF patients complain of symptoms mostly during p hysical activity, rather than at rest.
Through physical effort, cardiac output (CO) improves via an incorporated enhancement
in venous return, HR, peripheral vasodilation, and contractility. Abnormalities in each
one of these aspects of regular exercise recognized in HFpEF. (10)
Regular diastolic reserve with physical activity permits the ventricle to fill more essential
preload volume level, without causing a rise in filling pressure. Aged -heart recompense
its chronotropic reserve and contractility reducti on via enhancement of preload reserve.
Including diastolic abnormality and diastolic reserve impairment in HFpEF, the heart will
not be able to improve an increase in preload level during physical activity even with
increased filling pressure. This conditi on related to chamber stiffness and insufficiency
of relaxation. (10)
During activity in HFpEF, the systolic reserve is aggravated and reduced with decrease
contractility, EF and systolic velocities in course of physical exercise. Stress exercise
reveals t he failure to lower ESV, insufficiency in systolic function coupled with limited
improvement of EDV, which in turn will limit stroke volume. Systolic and diastolic
reserve dysfunctions in HFpEF are associated with, beta-adrenergic signaling
impairment, abn ormal calcium handling and ischemia of myocardium. (10)
Chronotropic incompetence found in patients with HFpEF. During exercise, beta –
adrenergic stimulation is limited and decreased stemming from elevated catecholamine's
in plasma and autonomic dysfunction . Which it is secondary to the sensitivity of baro –
reflex reduction. In these patients with HFpEF, heart rate recovery is prolonged after
exercise and abnormal at maximum activity. With these patients, exercising ability
interlinked with CO alternation , HR, and vascular resistance. (10)

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1.5.5. Ventricular -arterial coupling
Cardiovascular functionality oriented mainly to the relationship between LV together
with arterial sys tem, which currently termed as Ventricular -Arterial coupling (V -A
coupling). V -A coupling deformity associated with the stiffening of the arterial system
and LV. This abnormality frequently detected in elderly, diabetic and hypertensive cases
in HFpEF. V -A coupling, under regular physiological performance the blood rejected
from LV into a circulation system with minimal and limited change in blood pressure and
lesser energy. (11)
Each arterial elastance (Ea) and ventricular elastance (Ees) are tightly coupled to obtain
the ideal capability, with typical ratio Ea/Ees (0.5 -1.0). In HFpEF p atients, both o f Ea and
Ees are increased compa red to healthy people, a ratio of 0 /5 in the se patients infers that
the system is currently taking out its maximal performance. In HFrEF, the ratio is fivefold
greater, as a cause of afterload mismatch. At any elevation in afterload and/or preload can
harmfully increase the blood pressure level, due to ventricular arterial stiffening, which
can lead to diastolic relaxation impairment, which in turn, during stress will cause filling
pressure to increase. At any alternation ventricular elastance, it will give rise to various
blood pressure changes without to have a large impact on SV; yet, it increases the oxygen
consumption. Diverse studies pointed out the meaning of V A -coupling irregularity in
terms of exercise , in HFpEF where an inability to increase contractility and decrease
afterload. (11)

1.6. Clinical presentation
1.6.1. Signs and symptoms
Clinically, there are wide range s of symptoms and signs that may heart failure represent.
The cardinal symptoms are:
1. Worsening dyspnea .
2. Fatigue .
3. Dyspnea at rest .
4. Reduced physical activity .
5. Nocturnal cough.

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Signs such as:
1. Third heart sound ( gallop) .
2. Peripheral edema .
3. Elevated pressure of jugular venous .
4. Pulmonary crackles.
5. Hepatomegaly.
The signs most likely related to sodium / fluid retention, it enhanced by diuretic treatment.
The signs could not note in patients, that they are already under diuretic treatment. The
presence of HF can't be simply diagnosed through the signs and symptoms only because
the similar sympt oms also noticed in other diseases such as, anemia, pulmonary diseases,
obesity. Patient's history, must be always taken, to check out if the patients have a high
risk to develop HF. (1) (2)
1.6.2. Heart Failure Classification
The New York Heart Associat ion (NYHA ) functional -classification and the
American college of cardiology/ American heart association (ACC/AHA) are two widely
used methods for classifying HF patients.
1) NYHA classification depends mainly on the presence of symptoms severity due to
exerci se performance. It contain s 4-categories, class -I symptoms doesn’t appear
during physical -activity, class -II during normal activity symptoms might appear,
class -III symptoms of HF exist even with small activity, IV unable to adapt small
activity , discomfor t even with rest .
2) ACC/AHA staging highlights the HF progression and development, it contain s 4
stages. Stage ''A'' risk factors are present , without heart structure modifications or any
symptoms appearing. Stage ''B'' structural heart abnormality, symptom s and signs of
heart failure are absent. Stage C structural heart abnormality, with HF symptoms and
signs (current or prior). Stage ''D'' refractory HF needing spe cific interventions (end –
stage disease). (1)

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1.6.3. Diagnosis of HFpEF
The diagnosis of HFpEF is actually more difficult to be done, which includes a
number of steps (1), and it depending on exclusions of possible non-cardiac causes of the
demonstrated symptoms, l ike anemia or chronic pulmonary -diseases (2). Most recent
worldwide guidelines of HF highly recommended the following consideration to give the
diagnosis of HFpEF:
1) Symptoms/ signs , that are typical for heart failure .
2) Presence of left ventricular EF , over 50 %.
3) Specific structural heart abnormalities (Left atrium enlargement, Left ventricle
hypertrophy).

1.6.4. Tests
1. Biomarkers
The two commonest types are
1) B-type natriuretic -peptide (BNP )
2) N-terminal pro -B type natriuretic -peptide (NT -proBNP).
They produced by myocytes as a result of expanding forces on the heart chambers.
Remarkably, natriuretic peptides quantities raise d beside s worsening NYHA , and more
elevated , generally in HFrEF than HFpEF . BNP formation depen ds mainly on End –
diastolic wall -stress (EDWS). In HF pEF, patients have a smaller LV -lumen and thickened
LV walls ( concentric hypertrophy) . The EDWS in HFpEF is lesser than HFrEF, resulting
in, generating smaller stimulation for BNP formation.
2. Electrocardiogram
Various irregularities detected on ECG, like arrhythmias (atrial fibrillation, ventricular
extra -systole, ventricular tachycardia ), old MI, and indication of LV h ypertrophy. ECG
should perform for all patients in suspicion of HF. In the cases of normal ECG together
with the normal plasma level of BNP and NT -proBNP, HF is definitely u nexpected. (12)

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3. Echocardiography
Echocardiography holds a central part in every indicative method of HFpEF , and it is
regarded as one of the common beneficial tests , as to the point that external examination,
x-ray, and ECG will not provide enough details to differentiate among diastolic and
systolic HF . (12)
Echocardiography determine s the etiology, evaluate the severity of eccentric /concentric
remodeling, and delivers specifics of the LV performance, diastolic irregularities and EF
values. Identifying of LV diastolic disorders has long done most regularly with Echo –
Doppler linked with raised natriuretic peptides level. The diagnosis, concerning diastolic
dysfunction, can be establish ed through a number of echo -Doppler findings. During
diastole, blood movem ent via mitral valve hinges on the pressure gradient. This pressure
is at a maximum level right after mitral opening (E -wave). Subsequently, the pressure
gradient lowered, which represents a diastasis. In turn, atrial contracts resulting in a newly
created trigged pressure to push the maximum blood into ventricles (A -wave). (12)(13)
E/A ratio refers to the first indication for evaluating diastolic performance, any
abnormality in diastolic dysfunction could alter the pressure gradient which in turn will
cause a drop in E wave, the contraction of the atria will be stronger, which is demonstrated
with rising A -wave. (12)(13)
In valuing diastolic dysfunction, there is other essential Echo determination. The ESC
recommendation for establishing the HFpEF diagnosi s through E/e’ ratio when E/e’ is
over 15 . When E/e’ ratio less than 8 the diagnosis should be excluded, between 8 and 15
biomarkers values (BNP> 200pg/mL or NT -pro BNP>220pg/mL) should be taken in
consideration. E ’ presents frequently the early diastolic (lateral, septal) lengthening in
mitral annulus peak velocity. (12)
Additional useful echocardiographic – parameters in presence of HFpEF:
1. Index over 34 mL/m2 of LA -volume.
2. LV mas index over 115 g/m² ( males) and over 95 g/m² (females) .
3. E’ septal less than nine cm/s and lateral less than nine cm/s .

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1.6.5. Complications
1. Arrhythmias
Atrial fibrillation : in about a 3rd of patients, AF exists with long -term of HF. AF either
characterize as a trigger or even may result of HF. The extension of AF with expeditious
ventricular response could hasten HF , remarkably, in people with the pre -existing
dysfunction in the ventricles. (13)
AF happens with excessive LV abnormalities , following MI and it is leading to a negative
prognosis. Moreover, patients with HF and AF ha ve reached extremely the highest
possibility of thromboembolic complications along with stroke. (13)
Ventricular arrhythmias are frequent and typical in HF last stages. Continued ventricular
tachycardia is present in around 15% of the cases. In extremely p rogressed HF, patients
need mainly cardiac transplantation. When ventricular tachycardia is continuous, that
implies expanded prospect for repeated ventricular arrhythmias and cardiac death . (13)
2. Thromboembolism and Stroke
HF affects the stroke, includ ing thromboembolism, beside s general anticipations, the
yearlong rate is increasing by almost 3%. Features that triggering the higher
thromboembolic risk in cases with HF contain reduced CO, (blood stasis, in expanded
heart chambers), irregularities in loc alized wall movement, and interlinked AF . (13)
HF patients, concurrently with persistent venous insufficiency could remain motionless,
which adds to their raised possibility of thrombosis, like pulmonary embolism and deep –
vein thrombosis. (13)
3. Cardiac Cachexia
It is a disorder caused by HF, its presence shows higher mortality and unique from
essential factors such, EF and age. It describes an influential predictive aspect of
extremely poor prognosis. Cardiac Cachexia (CC), which is an incidental unexpe cted
reduction in body -weight (more than 7% of body -weight in half a year). The clinical
effects of CC are impacted by, weight reduction and systemic inflammation, which occur
with CC progression. (14)

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4. Kidney dysfunction
Decreased kidney capacity well n oticed between HF patients, particular because the
complexity of HF besides numerous disorders coupled to HF (like DM). Investigations
submit that in cases with Hf and decreased kidney performance multiplies the risks
towards heart complications, which inc lude hospitalizations and even death. (15)

1.7. Treatment and M anagement
All clinical trials failed to achieve efficiency in order to reduce mortality and morbidity
cases in HFpEF. Present -day guidelines for HFpEF handling and management , highly
recommend ed A. treatment and classification of main etiological factor that involved in
HFpEF development, B. comorbidities treatment, which will worsen and complicate the
HF, C. Symptoms control and prevention of Bradycardia and tachycardia, balance HR to
metaboli c requirements. (16)(17)
Indeed, the best possible control of these considerations including non – pharmacological
and pharmacological treatment options. (17) (16)
1.7.1. Non-pharmacologic therapy
There are several common non -pharmacological therap ies shoul d be added during HFpEF
patients handling. It consist s of important aspects and steps such as patients education,
lifestyle and diet attention, excessive weight prevention, exercising, limited sodium
intake (less than 1 g/day), blood pressure follow up, we ight daily monitoring, high fluid
intake avoidance but well balanced to kidneys performance. However, if the patient is
under diuretic treatment and fluid restriction it could lower glomerular filtration rate
(GFR) and cause acute kidney damage. Few amount s of peripheral edema identified ideal
volume intake in these patients. Numerous studies have included exercise in HFpEF
patients that may enhance exercise tolerance; however , it may be varying from patient to
another. (18)(19)

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1.7.2. Pharmacological ther apy
The treatments of HFpE F focus mostly on comorbidities, risk factors and symptoms and
signs reduction. Extremely limited results research studies are obtainable. Hypertension
is the first line target that must be treated. AHA/A CC guidelines verify the u se of:
1. Beta-blockers (BBs)
Which enhance and prolong the diastolic filling time, minimizing myocardial ischemia,
atrial fibrillation and blood pressure controlling. (18)
2. Angiotensin covering enzyme -inhibitors (ACE -I)
Have venous and arterial vasod ilation effect. Fibrosis and ventricular hypertrophy
increase due to angiotensin II, both of them, which are contributing factors for HFpEF.
In addition to vascular remodeling and vasoconstriction. The achievable point for
treatment of HFpEF by angio tensin II production inhibition, it must be given in all cases
with atherosclerotic and diabetic cases. ACE -I use may lead in some patients to
hypotension, hyperkalemia, angioedema and renal failure. It needs to be provided with
minimal dosage at the starting of the treatment to steer clear any kind of unexpected
complications . (19) (20) (21)
3. Angiotensin receptor -blocker (ARBs )
In case contraindications as well as allergic sensitivity for ACE -I, ARBs will be an
alternative . ARBs, alike ACE -I, assist blunt the da maging implications of Angiotensin,
in spite of this ARBs exert its effect additionally by blocking the connection between
Angiotensin II and its receptor. Similar to ACE -I, starting with lower dose of ARBs and
monitoring blood pressure, renal function and sodium potassium levels to prevent any
treatment complications such as renal failure, hypotension , decrease in sodium serum
level and hyperkalemia. In prese nce of contraindications or ACE -I, and ARBs
intolerance . (19) (20)
4. Hydralazine and Isosorbide dini trate
They a re additional vasodilatations p referred as alternative therapy, Volume level over –
load regulated mainly with diuretics (thiazide or furosemide), which must be used to drop
and reduce the severity of signs and symptoms related to pulmonary hype rtension such
as edema and breathlessness. (20) (21)
Anticoagulation therapy to decrease the possibility of thromboembolism and AF.
Amiodarone can be given to patients with persistent or proximal AF; in turn, amiodarone
will reduce the presence of AF . (21)

21
2. SPECIAL PART
2.1. Introduction and Aim of the study
The diseases that concomitantly present in a syndrome just as HF could aggravate
management and also can adverse skeptical outcomes.
An additional study, of the Med -Services Center, confirmed that ne ar 55% of affected
persons indicating five long -term comorbidities. But regarding ESC was found that 74%
of HF patients have 1 associated comorbidity, the most found comorbidities were
Anemia, Diabetes, and CKD.
Overall, over 25% of HF individuals provide, renal disorders and pulmonary as comorbid,
that is involving mainly in expanded morbidity moreover mortality in total HF
community.
EF measurements in existence of HF is subdividing the syndrome into 2 pathological
groups, which differ from each other in pathophysiology and etiology. Taking 50% of EF
value as a limit to differ between them. Preserved EF is greater than 50% and reduced EF
is less than 40%. Recently guidelines established a new subgroup with mid -range (40 -50
EF).
Data about the findings of H FrEF vs. HFpEF diversified in numerous populations,
however, details imply HFpEF affiliated to substantial morbidity/mortality, meets or
equals that of HFrEF. Surprisingly, one present report revealed that, while the same BNP
rages were matched cross EF va lues, the probability for adverse consequence’s was the
same as in HFrEF and HFpEF.
The complete prevalence of clinic admittance is equal among the two groups, yet HFpEF
individuals possess greater events of non -HF admissions. HFrEF individuals include an
increased HF event that causes to hospital admissions.
Despite, some trials looked at the differential connection between, "comorbidities"
concurrently with the impact in HFpEF suffers.
In our study, we aim to assess the prevalence of the commonest six co morbidities ( DM,
CKD, COPD/Asthma, liver diseases, Anemia and obesity) in a group of 61 patient
admitted in ASCAR, Hospital during, 2015 -2019 and correlate the comorbidities and
their association with, etiology, EF, prognosis (assessed by readmissions in hospital)
together beside Aging.

22
2.2. Material and Methods .
Our research is a retrospective study, which evolved 61 patients diagnosed with HFpEf.
The study included both genders, with different ages who admitted to ASCAR Hospital
between the years April 2015 – April 2019.
The patients came to the hospital with decompensated HF and represented with different
symptoms, mostly with dyspnea, palpitation and fatigue. Depending on presented
symptoms among each patient, it was needed to hospitalize them, and to p rovide them
further investigations and care. BP and ECG were comp leted for every single patient
throughout the hospitalization period.
The investigations included Echocardiography in order to obtain the EF, valvulopathies,
and hypertrophy in each patient. Also determining E/A ratio which is the most specific
parameter in order to diagnose diastolic insufficiencies.
Some comorbidities were verified by the blood analysis, such as glucose level in the
presence of DM, Anemia depending on hemoglobin levels (unde r 12 mg/dl). BMI was
calculated to classify the obesities stages.
Spirometer was produced for each of the patients in the presence of respiratory diseases,
such as COPD, and Asthma because those 2 pathological states could complicate the
handling of HFpEF.
Liver steatosis was discovered by abdominal Echography, which confirmed the liver
modifications. CKD by measuring the GFR formula depending at creatinine level in the
blood.
Comorbidities that detected in every patient, encountered in worsen the predicti on
including leading to readmission to the hospital. Hospitalizations days were gathered
according to hospitals information. Toward each case was given an NYHA class in
sequence to account the presence of the symptoms. After gathering all this information
by each patient individually, statistical analysis (Excel) and SPSS were accomplished in
order to find the correlation between the comorbidities and their effects on each patient’s
health .

23
2.3. RESULTS
Gender distribution

HFpEF affects much females, rather than m ales, implying gender to have a primary
feature in disease existence. Obviously, the risk features in HF are identical among both
genders, nerveless, there exist vary in their related distribution.
Our study contained 61 randomly patients, that evolved HFp EF. Regarding to the
available patient’s information’s, 19 of the patients are males and 42 are females, we can
almost say, that the proportion is almost 1:2. It noticed clearly in this graph that female
gender is mostly affected.

Figure 1. Gender distr ibution

41
19
051015202530354045
Female MaleGENDER

24
Age Distribution

Age, valued as a critical risk factor in HF development. In this chart was uncovered that
3% of the patients are inserted between 40 -49 years, 13% between 50 -59, 30% within 60 –
69, and 20% between 80 -89.
It is clearly remar ked that the majority of the HF suffers are older than 60. The main age
average is 67 regarding our collected data.

Figure 2.Age distribution

28182112
40-4950-5960-6970-7980-89
0 5 10 15 20 25Composition by age Group

25
Symptoms Proportions
Tiredness, particularly fatigue appears mainly, as a cause of limited blood entering into
the muscles tissues, resulting from the decreased working potential of the heart's muscle.
Which regarded one of crucial HF symptoms. Between our collected patient's data, 70%
in the presented cases had fatigue as a symptom.
Dyspnea was proved in per cent of 76% which is the highest among the patients caused
by irregular fluids accumulations in the lung. This established fluid contributes to
breathing difficulties.
Palpitation reveals an abnormal beating of the heart, in a proportion of 47%, which had
been caused by the acceleration of the heart to recompense the lack of pumping ability.
This may cause chest pain, dyspnea, and dizziness.
Edema, which is the lowest percentage in this category with nearly 13%. It could be the
lowest percentage because all the diagnosed HFpEF patients are mainly under diuretic
treatment. It wasn’t noticeable in a high percentage, which is given to avoid edema and
excessive blood accumulation as a cause of HF.

Figure number 3 . Symptoms distribution

Dyspnea
Fatigue
Palpitatoin
Edema0%10%20%30%40%50%60%70%80%76%
70%
47%
13%symptoms distribution (%)

26
Co-morbidities in perce nt

In more aged commonality, comorbidities are extremely current, which makes them
reporting to a higher non -HF level of admissions. These comorbidities, which we took in
our study were metabolic diseases, respiratory complications, renal and hematologica l
abnormalities.
In this chart, only 8% of the patients didn’t show any of the above mentioned
comorbidities comparing to 92% patients with represented comorbidities.

Figure 4 . Comorbidities in Percent among patients

8%
92%comorbidities percentage
without any comorbidities
one to four comorbidities

27
Co-morbidities in numbers

The comorbidities among all the collected d ata for the patients, represented in numbers,
how many comorbidities are found among the diagnosed HFpEF, which could lead to
worsening the prognosis and increasing the readmission rate.
In this graph was found that 12 patients have 3 co -morbidities, 23 patients suffer from 2
comorbidities, 15 patients developed 1 comorbidity, 6 of them recognized with 4
associated comorbidities which is the highest number regarding our data, and only 5
patients without any significa nt comorbidity.

Figure 5 . Number of comorbidities

51523
12
6
0 0
0 1 2 3 4 5 6patients numbers
Comorbidities NumbersComorbidities Numbers

28
CKD Proportion
Renal complications, may possibly exacerbate HFpEF by a variety of mechanisms such
as increased inflammation, anemia, sympathetic activation, and fluid increased retention.
Those mecha nisms are combining a new situation of more additional risks that may
strongly involve in increasing mortality and worsening HFpEF. In this graph, it can be
assumed that the severity of CKD ranged in between stage 3 21%, and stage 2 18%, and
with less occu rrences of stage 4(2%). 59% of the patients didn’t reveal any CKD.

Figure 6 . CKD proportion Among Patients

There is a significant worsening of chronic kidney disease with age .
59%
18%21%
2%
0%10%20%30%40%50%60%70%
no stage 2 stage 3 stage 4Chronic Kidney Disease Proportion Among Patients
Age group
Total less than 60
(n=10) 60-69
(n=18) 70-79
(n=21) equal or
over 80
(n=12)
Chronic Kidney
Disease (stages) 0 7 15 10 3 35
1 0 0 0 1 1
2 2 2 6 1 11
3 0 1 5 7 13
4 1 0 0 0 1
Ordinal values association: Gamma = 0.513 ± 0.150; T = 3.283; p = 0.001**
** p<0.01; highly statistical significance

29
Liver Steatosis
Liver steatosis was indicated for 31% of patients beside HFpE F, 67% noticed without any
liver modifications, and only 2% with liver cirrhosis. Liver steatosis is found mainly
within patients who are suffering from weight problems and metabolic diseases such as
DM.
Liver steatosis is connected to an important prospec t of heart disorders in particular,
“CAD” which it took into consideration in this study as one of the co -morbidities of
HFpEF.

Figure 7 . Liver steatosis, Cirrhosis

1, 2%
19, 31%
41, 67%Liver steatosis
liver cirrhosis
liver steatosis
no

30
Anemia proportion
Anemia is one of the comorbidities that affirmed in elderly peopl e with HF among our
collected data, which explains the relationship with more severe findings. Anemia may
be more prevailing in HFpEF cases, and therefore involved in raised hospitalizations with
over-all mortality.
This graph represents 26% of patients wi th anemia (Hb < 12 g/d l) and 74% didn’t this
disease.

Figure 8. Anemia proportion

Characteristics for age group: numerical variables
Age groups
Variable less
than 60
(n=10) 60-69
(n=18) 70-79
(n=21) equal or
over 80
(n=12) ANOVA
combined
p-value ANOVA
linearity
p-value Eta-
squared
Ejection
(a)fraction 0.57 ±
0.093 0.58 ±
0.074 0.58 ±
0.059 0.62 ±
0.077 0.442 0.147 0.046
(a)Hemoglobin 14.2 ±
1.67 13.2 ±
1.82 13.1 ±
1.9 12.3 ±
2.25 0.214 0.029* 0.089
(a) mean ± standard deviation
* p<0.05; statistical significance

It was notified that the hemoglobin statistically decreases with age, while toward the EF
there is not any statistically significant variation among the age groups.
26%
74%AnemiaAnemia
No
Anemia

31
COPD/ Asthma

HFpEF persons, sometimes have COPD or pulmonary issues like asthma, which is part
of maximizing symptoms. Furthermore, HF individuals are inclined to h ave COPD
detection. Likewise, even the reduction of COPD cases in HFpEF, many pulmonary
disorders that form severe symptoms and poor consequence. In the chart beneath, was
declared that 53% of the patients didn’t develop any Respiratory complications,
comp aring to 47% who had. Depending on spirometer and x -ray outcomes, 35% of Hf
patients developed COPD, 9% had asthma as respiratory condition, and the lowest
percentage was for pulmonary fibrosis with 3% of occurrence.

Figure number 9. COPD/Asthma among p atients

35%
9%
3%
53%COPD/Asthma
COPD
Asthma
Pulmonary fibrosis
absence

32
Diabetes mellitus proportion

DM in HF, is directly dependent, individuals with DM get a greater risk of generating HF
and also patients with HFpEF are near risk of producing DM. The presence of DM in
between HfpEF cases is current, and it has influences on hospitalization rates.
Regarding to our collected cases, 28% of our patients have DM, 72% haven’t existent,
but the risk of DM is present.

Figure 10. Diabetes mellitus

28%72%
0%10%20%30%40%50%60%70%80%
DM NoDiabetes

33
Obesity proportion among patients

Globally, obesi ty took a widesp read proportion , which is one amongst the standard
metabolic -disorders in HfpEF. Obesity , consists of different harmful impacts on the heart,
mediated over volume alternations, systemic inflammations, and HTN elevated risk,
which expected to progress HfpEF condition.
The graph shows that almost 51% of the admitted patients reported as normal weight, and
49% with obesity. 35% of obese patients reported with obesity Grade 1, 9% with grade 2
(severe), and 5% with grade 3 obesity (morbid).

Figure 11. Obesity Grades.

51%
35%
9%
5%obesitynormal
weight
Grade 1
grade 2

34
Ischemic Heart Diseases

With this graph, CAD was contained in 33% of the patients, which it is one of the etiology
that evident in our gathered data, 30%having stable angina, 3% with unstable angina and
67% w ithout any CAD progression. CAD, caused by plaque in heart main arteries, this
plaque deals with a drop of the blood flow into the muscle.

Figure 1 2. Ischemic Heart Diseases.

67%
30%
3%
0%10%20%30%40%50%60%70%80%
No Stable Angina Unstable AnginaIschemic Heart Diseases

35
Hypertension Grades distribution

HTN , continues as one with the critical factor in HFpEF progression. C oncerning 61
patients in our study, was determined that each patient had elevation in blood tension,
with varying grades.
HTN comprises of 3 degrees depending on systolic (above 140 mmHg) and diastolic (>90
mmHg) pressure. During our investigations, notifi ed clearly that all no patient has normal
blood pressure by admission. 20% of the cases present grade with limited cardiovascular
risk, 56% which is the highest percentage between the patients, with a higher prospect of
cardiovascular complications, regard ed as stage 2, and stage 3 represent 24% of the
patients which is the worst stage of HTN, with an expanded risk of complications.

Figure number 13. Hypertension grades distribution

0%10%20%30%40%50%60%
Normal Grade 1 Grade 2 Grade 30%20%56%
24%Hypertension distribution (%)

36
Atrial Fibrillation

AF and HFpEF are age -dependent circumstances, w hich are expanding in incidence,
mostly coexist, and even show clinical related characteristics. There are highly developed
connections in HFpEF and AF, such basic risk factors and large currency of AF in causes
of HFpEF.
Studies failed to distinguish if A F or HFpEF occurred firstly, because AF may alters the
Echo -variables and BNP mistake detection.
In this graph, was noticed that 40% of the patients (HFpEF diagnosed) AF was present,
and 60% didn’t develop any arrhythmias but they still under high risk.

Figure 1 4. Atrial fibrillation

40%
60%Atrial Fibrillation
Atrial Fibrillation Not present

37
Pulmonary Hypertension

In the graph below, was noticed that 31% of HFpEF patients developed PH, and 79% of
patients haven’t. PH creates inflammation in the lined pulmonary artery cells. Those
alternations cause to narro wing the blood vessels and difficulty in blood movement.
Subsequently, the heart is inefficient to pump the blood completely through pulmonary
arteries toward, which maximizes the tension in arteries. PH has a straight reaction to
lessened relaxation also progressed inflexibility of LV, which is a factor for prognosis
worsening and mortality.

Figure 1 5. Pulmonary hypertension

Pulmonary
hypertension
31%
absence
69%Pulmonary Hypertension
Pulmonary hypertension absence

38
Diagnosed Valvulopathies
Echocardiography was previously used in order to confirm the existing diagnosed
valvulopathies, as w ell as to observe their progression.
The Graph below represents the valvulopathies that were presented among HfpEF
patients.
Mitral Insufficiency, which has the most dominant occurrences with percentage of 60%,
which is the highest compar ed to other valvul opathies. Aortic Insufficiency, which is
second most common valvular diseases in this category with occurrences of 38%, Aortic
Stenosis 13% and Tricuspid insufficiency 18% represent the lowest appearance according
to our collected data.

Figure 1 6. Diagn osed Valvulopathies

0%10%20%30%40%50%60%
aortic insufficiency Mitral insufficiency Aortic stenosis tricuspid
Insufficiency38%60%
13%18%Diagnosed Valvulopathies (%)

39
NYHA Classification
According to the data that had been collected from sixty -one patients, six patient has
reported the first class, thirty -five patient has shown the second class, seventeen patient
has detailed the third class, a nd three patient has reported the fourth class .
Due to sixty -one patients' information, we may conclude that both classes two and three
are the main patients -reported symptoms.
Figure 1 7. NYHA Classifications

Characteristics for age group: ordinal variab les
Age group
Total less than 60
(n=10) 60-69
(n=18) 70-79
(n=21) equal or
over 80
(n=12)
NYHA
classification 1 3 2 1 0 6
2 3 12 16 4 35
3 4 4 3 6 17
4 0 0 1 2 3
Ordinal values association: Gamma = 0 .362 ± .169; T = 2.004 ; p = 0 .045*
* p<0.05; statistical significance

We can observe that there is a significant association between the NYHA
degrees and the age groups ( HFpEF is worsening with age) . 10%57%
28%
5%
0%10%20%30%40%50%60%70%
1
The Percentage of PatientsNYHA Functional Classification of Heart Failure
Class1
Class2
Class3
Class4

40
Co-morbidities, Age correlation
This graph is demonstrating the comorbidities (in percentage ) among every patient's
group. The patients were sorted into 5 smaller groups determined by their age, to concern
the maximum comorbidities proportion among patient’s ages.
A. Group 1 which is the youngest group in this study, between ages 40 -49 gives the
peak percentage of 4 2% existed comorbidities.
B. Group 2 patients younger than 60 and older than 50 shown with almost similar
value, 40%.
C. Group 3: in a range of 60 -69 years patients with 37% of comorbidities.
D. Group 4: it noticed a lower percentage of comorbiditi es between ages 70 -79
detected with 31%.
E. Group 5: which is the eldest patients category in this investigation, with patients
between 80 -89 years, corresponds to the lowest comorbidities occurrence with
29%.

Figure 1 8. Comorbidities, Age correlation, neg ative correlation.

42%40%37%
31%29%
0%5%10%15%20%25%30%35%40%45%
40-49 50-59 60-69 70-79 80-89
age rane Comorbidities age correlation

41
Hospitalizations Days/Age Correlation

The diagram below signifies the correlation between patients Age and the hospitalization
days among each patients group.
The patients were categorized into 5 groups, depending principally on pat ient’s age. The
days were counted in averages concerning the days that each patient stayed in the hospital.
Patients between ages:
1) 40-49 were hospitalized on an average of 5.5 days.
2) 50-59 of the patients had 6.6 averaged days of hospitalization.
3) 60-69 of t he patients stayed in the hospital on an average of 7 days.
4) 70-79 had 7.6 as averaged of hospitalized days.
And the last group which consists mainly of the oldest patients between years 80 -89 of
the highest average of hospitalizations days which was 9. It can be recognized that the
averages were rising beside increased patient’s ages.
Figure 1 9. Hospitalization days among patients Group

5.56.6257.17.6679
012345678910
40-49 50-59 60-69 70-79 80-89days number
ageHospitalisation days

42
Hospital Readmission due to Age
The graph reports hospital readmissions in the last 5 years for each patient. Depending on
the hospital's data, that were obtainable for each patient's readmission. The patient's sub –
arranged into age -ranges in order to maintain the highest readmission among each group.
After subgrouping the 61 patients into 5 central groups, and calculation the average for
each group readmission, it was noticed that the patients that were older than 60 years had
the maximum readmission average. The lowest readmission average was for the patients
between 40 -49 with average 1 readmission and 50 -59.
It can be a ssumed that this graph provides a positive correlation between aging and
readmission.

Figure 20. Hospital readmission due to Age group.

1
1.5
2.2
2.4
2.5
40-49 50-59 60-69 70-79 80-89HOSPITAL READMISSION DUE TO THE
AGE

43
2.4. Discussion Part
Heart -failure, with a preserved -EF, usually abbreviated to HFpEF, comprises
diverse heart con dition s which have in common the presence of left ventricular EF over
50%.
HFpEF remains in a rise in the developed countries, certainly resulting from the dominant
incidence of risk factors, like, aging , HTN, metabolic syndromes, female gender, obesity
and renal dysfunction.
Over 85% of the patients are mostly hypertensive with variety of HTN grades. HTN most
definitely is a substantial factor in this syndrome. HFpEF was categorized previously
under the term of “diastolic HF”. Nevertheless, current reports propose a much more
heterogeneity besides its pathophysiology. There are divers pathophysiological patterns
that all doubted in HFpEF, which are broadly notified in circumstances, whenever stress
occurs in the cardio -vascular system. According to the ev idence, HF is combined
syndrome affected by various etiologies. Furthermore ensued with non -cardiac risks that
might guide to worse condition in this study we set out to affirm the correlation within
older patients compared with younger -old patients (HF diag nosed) and the influences of
the comorbidities on each group. The various frequent cases at admission were, dyspnea
and tiredness. Prese ntly, three standards need to m eet to verify each determination:
1) Clinical indications
2) EF above 50%
3) Confirmation of cardi ac insufficiency
We classified the patients according to their age, into 5 subgroups. It was clearly noticed
according to our results that readmission for older people was much higher than patients
under 70.
It was observed even in presence of on e comorbi dity among patients older than 70, the
readmission was higher compared to the younger -old group while they have higher
comorbidities incidences. That improves our correlation that age is fully associated with
readmission and development of HFpEF. Life expe ctancy in our days is higher among
the population that lead to the presence of several diseases and syndromes that are
strongly linked to age.

44
In a study that has been done between 1984 and 2011 the patient's number of HFpEF is
dramatically increasing due to several aspects and less effective medications for treating
this kind of syndrome.
Female gender , is well spread noticed in our data with ratio of 2:1, hypertensive was
present in 100% of the patients that are facing HFpEF and valvulupaties 75% as main
well seen etiology and cause for developing HF, one comorbidity and age above 75 is the
central cause to readmit the patient to hospital, in higher rate according to the data that
we collected. Ischemia, insufficient myocardium oxygenation is seen in an el evated
percent of HFpEF individuals. This ischemia could be secondary to CAD or even due to
earlier explained alternations in the microvasculature.
Cellular deteriorations or cardiac -senescence arises within regular aging. Strictly appears
like the indicat ions of HFpEF. Predominantly , lack of cardiac reserve, lessened vascular
compliance, as well as a diastolic disorder are indicative of the two processes. It is often
mentioned that HFpEF basically corresponds to the acceleration of regular signs of aging.
Specifications for the medical diagnosis of the diastolic disorder and diastolic cardiac
failure continue to be imprecise. This makes it critical to perform accurate clinical trials
of therapy choices for HFpEF.
The co -existence for diastolic moreover syst olic failure is generally present, which could
intensify the clinical condition if the patients represent including no n-ischemic and
cardiac etiologies of HF.
The progress concerning to HFpEF, furthermore its clinical development remains poorly
explained i n opposition to HFrEF. Notwithstanding that, cases with HFrEF and HFpEF
seem to hold alike outcomes in courses of hospitalization including death , causes
regarding mortality within patients, alter mainly, Still, between patients in more severe
HF (NYHA II -IV)
Cardiovascular mortality, including heart attacks also sudden cardiac death, implied the
dominant purpose toward population -based investigations .
Until presently, it was estimated that the patients with “diastolic abnormalities” even with
the appearan ce of pulmonary edema held a greatly better prognosis that HFrEF patients.
Yet in 2006, 2 studies were published in the “New England” journal of medicine,
performed a suggestion, that the prognosis for both syndromes is similar.

45
2.5. Conclusion

1) Age and C omorbidities profile are strongly associated with the presence of
HFpEF.
2) The non-cardiac comorbidities must be well treated and highly controlled in
younger ages, otherwise , the prognosis will be dark among those patients with
HFpEF .
3) Female gender is more affected in HFpEF when it compared with the male gender
with proportion 2:1 .
4) Hypertension is the most dominant etiology in -between HFpEF patients, which
was noticed among all the patients with a variety of stages.
5) Hospital readmission is strongly correlate d to age, which is higher among older
HFpEF patients, mainly above age 60 with at least one associated comorbidity
such as, anemia, chronic kidney disease , and diabetes mellitus.

46
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