HEART FAILURE ( based on Harrison's Textbook of Medicine ) .pdf

This presentation is about heart failure.

The definition , phenotypes and etiology , stages , pathophysiology , evaluation of a patient with heart failure and the differential diagnoses are described in this.

1. HEART FAILURE

2. Contents
●Definition
●Phenotypes & causes
●Stages of heart failure
●Pathophysiology
●Evaluation of a patient with heart failure
●Differential diagnoses of heart failure

3. Definition
Heart failure (HF) is a common final pathway for most chronic cardiovascular diseases
including hypertension, coronary artery disease, and valvular heart disease.
The American College of Cardiology Foundation/American Heart Association
(ACCF/AHA) and Heart Failure Society of America (HFSA) guidelines define HF as a
complex clinical syndrome that results from any structural or functional
impairment of ventricular filling or ejection of blood leading to cardinal
manifestations of dyspnea, fatigue, and fluid retention.
The European Society of Cardiology’s (ESC) definition emphasizes typical symptoms
(e.g., breathlessness, ankle swelling, and fatigue) and signs (e.g., elevated jugular
venous pressure, pulmonary crackles, and peripheral edema) caused by a
structural and/or functional cardiac abnormality, resulting in a reduced cardiac
output and/or elevated intracardiac pressures at rest or during stress.

4. Chronic heart failure describes patients with longstanding (e.g., months to years)
symptoms and/or signs of HF typically treated with medical and device therapy.
Acute heart failure, previously termed acute decompensated HF, refers to the
rapid onset or worsening of symptoms of HF.
Most episodes of acute HF result from worsening of chronic HF, but ~20% are due
to new-onset HF that can occur in the setting of acute coronary syndrome, acute
valvular dysfunction, hypertensive urgency, or postcardiotomy syndrome.
Similarly, acute pulmonary edema in HF describes a clinical scenario in which a
patient presents with rapidly worsening signs and symptoms of pulmonary congestion,
typically due to severe elevation of left heart filling pressure.

6. Phenotypes and Causes
HF with Reduced Versus Preserved Ejection Fraction
Epidemiologic studies have shown that approximately one-half of patients who
develop HF have reduced left ventricular ejection fraction (EF; ≤40%) while the other
half have near-normal or preserved EF (≥50%).
Because most patients with HF (regardless of EF) have abnormalities in both systolic
and diastolic function, the older terms of systolic heart failure and diastolic heart
failure have fallen out of favor.
Classifying patients based on their EF (HF with reduced EF [HFrEF] vs HF with
preserved EF [HFpEF]) is important due to differences in demographics,
comorbidities, and response to therapies .
The diagnosis of HFpEF is often more challenging due to the need to rule out non
cardiac causes of shortness of breath and/or fluid retention.

9. Heart Failure with Mildly Reduced EF (HFmrEF)
Patients with HF and an EF between 40 and 50% represent an intermediate group that
are often treated for risk factors and comorbidities and with guideline-directed medical
therapy similar to patients with HFrEF.
They are felt to have primarily mild systolic dysfunction, but with features of diastolic
dysfunction.
They may also include either patients with reduced EF who experience improvement
in their EF or those with initially preserved EF who suffer a mild decline in their
systolic performance.
Unlike the ACCF/AHA and HFSA guidelines, the ESC guideline has identified
HFmrEF as a separate group in order to stimulate research into underlying
characteristics, pathophysiology, and treatment.

11. HF with Recovered EF
A subgroup of patients who are diagnosed with HFrEF and treated with guideline-directed
therapy have rapid or gradual improvement in EF to the normal range and are referred to as
having HF with recovered EF (HFrecEF).
Predictors of HFrecEF include younger age, shorter duration of HF, nonischemic etiology,
smaller ventricular volumes, and absence of myocardial fibrosis.
Specific clinical examples include fulminant myocarditis, stress cardiomyopathy, peripartum
cardiomyopathy, and tachycardia-induced cardiomyopathy, as well as reversible toxin
exposures such as chemotherapy, immunotherapy, or alcohol.
Despite recovery of EF, patients may remain symptomatic due to persistent abnormalities in
diastolic function or exercise-induced pulmonary hypertension.
For patients who become asymptomatic, withdrawal of therapy can lead to recurrence of HF
symptoms and decrease in EF. In general, prognosis of patients with HFrecEF is superior to
that of patients with either HFrEF or HFpEF.

13. Pathophysiology of heart failure

14. HF is a progressive disease
HFrEF is a progressive disease that typically involves an index event followed by
months to years of structural and functional cardiovascular remodeling.
The primary event may be sudden in onset, such as an acute myocardial infarction;
more gradual, as occurs in the setting of chronic pressure or volume overload;
inherited, as seen with genetic cardiomyopathies; or congenital disease.
Despite an initial reduction in cardiac performance, patients may be asymptomatic or
mildly symptomatic for prolonged periods due to the activation of compensatory
mechanisms that ultimately contribute to disease progression.

15. Ventricular remodelling
As demonstrated in both animal and human studies, different patterns of ventricular
remodeling occur in response to excess cardiac workload.
Concentric hypertrophy, in which increased mass is out of proportion to chamber
volume, effectively reduces wall stress under conditions of pressure overload (e.g.,
hypertension, aortic stenosis).
By contrast, an increase in cavity size or volume (eccentric hypertrophy) occurs in
volume overload conditions (e.g., aortic regurgitation, mitral regurgitation)
In both forms of remodeling, an increase in ventricular mass is accompanied at the
cellular level by myocyte hypertrophy and interstitial fibrosis, at the protein level by
alteration in calcium-handling and cytoskeletal function, and at the molecular level by
reexpression of fetal genes.

16. In addition to cell loss from necrosis,
myocytes that are unable to adapt to
remodeling stimuli may be triggered
to undergo apoptosis or programmed
cell death.
Further impairment in pump
function and increased wall stress in
the face of systemic vasoconstriction
and loss of neurohormonal
adaptation can lead to afterload
mismatch. These events feedback on
remodeling stimuli, setting up a cycle
of deleterious processes resulting in
clinical HF.

18. Neurohormonal activation
Activation of the sympathetic nervous system (SNS) and
renin-angiotensin-aldosterone system (RAAS) plays a critical role in the
development and progression of HF.
Initially, neurohormonal activation leads to increases in heart rate, blood pressure, and
cardiac contractility and retention of sodium and water to augment preload and
maintain cardiac output at rest and during exercise. Over time, these unchecked
compensatory responses lead to excessive vasoconstriction and volume retention,
electrolyte and renal abnormalities, baroreceptor dysfunction, direct myocardial
toxicity, and cardiac arrhythmias.
At the tissue level, neurohormonal activation contributes to remodeling of the heart,
blood vessels (atherosclerosis), kidneys, and other organs and the development of
symptomatic HF.

20. Activation of neurohormonal systems in heart failure.

Decreased cardiac output in heart failure (HF) results in an “unloading” of high-pressure
baroreceptors (circles) in the left ventricle, carotid sinus, and aortic arch, which in turn causes
reduced parasympathetic tone. This decrease in afferent inhibition results in a generalized increase
in efferent sympathetic tone and nonosmotic release of arginine vasopressin from the pituitary.

Vasopressin is a powerful vasoconstrictor that also leads to reabsorption of free water by the
kidney. Afferent signals to the central nervous system also activate sympathetic innervation of the
heart, kidney, peripheral vasculature, and skeletal muscles. Sympathetic stimulation of the kidney
leads to the release of renin, with a resultant increase in circulating levels of angiotensin II and
aldosterone.

The activation of the renin-angiotensin aldosterone system promotes salt and water retention,
peripheral vasoconstriction, myocyte hypertrophy, cell death, and myocardial fibrosis.

Although these neurohormonal mechanisms facilitate short-term adaptation by maintaining blood
pressure, they also result in end-organ changes in the heart and circulation.

21. Vasodilatory hormones
While RAAS and SNS activation contributes to disease progression in HF, a number of
counterregulatory hormones are upregulated and exert beneficial effects on the heart,
kidney, and vasculature.
These include the natriuretic peptides (atrial natriuretic peptide [ANP] and B-type
natriuretic peptide [BNP]), prostaglandins (prostaglandin E1 [PGE1 ] and prostacyclin
[PGI2 ]), bradykinin, adrenomedullin, and nitric oxide.
ANP and BNP are stored and released primarily from the atria and ventricles,
respectively, in response to increased stretch or pressure. Beneficial actions are
mediated through stimulation of guanylate cyclase and include systemic and
pulmonary vasodilation, increased sodium and water excretion, inhibition of renin and
aldosterone, and baroreceptor modulation.

22. Bradykinin and natriuretic peptides are inactivated by neprilysin, a membrane by
peptidase, which explains in part the beneficial clinical impact of angiotensin
receptor–neprilysin inhibition in HF .
Natriuretic peptide levels can be used to assist in the diagnosis and risk stratification of
patients with HF.

23. Endothelin, Inflammatory Cytokines, and Oxidative
Stress
Endothelin is a potent vasoconstrictor peptide with growth-promoting effects that may play an
important role in pulmonary hypertension and right ventricular failure. Endothelin is released
from a variety of vascular and inflammatory cells within the pulmonary circulation and
myocardium in response to increased pressure and has direct deleterious effects on the heart,
leading to myocyte hypertrophy and interstitial fibrosis.
Unlike RAAS and SNS inhibition, however, endothelin blockade has not been shown to slow
the progression of clinical HF but is beneficial for treatment of pulmonary arterial hypertension
.
Other factors that have the potential to cause or contribute to ventricular remodeling in HF
include inflammatory cytokines such as tumor necrosis factor (TNF) α and interleukin (IL) 1β
and reactive oxygen species such as superoxide. Potential sources of these biologically active
substances are the liver and gastrointestinal tract. The role of anti-inflammatory and antioxidant
therapies remains unproven.

24. Dyssynchrony and Electrical instability
In up to one-third of patients with HF, disease progression is associated with prolongation of
the QRS interval. Electrical dyssynchrony in the form of left bundle branch block (LBBB) or
intraventricular conduction delay results in abnormal ventricular contraction.
Correction of electrical dyssynchrony with left or biventricular pacing can improve
contractile function, decrease mitral regurgitation, and reverse ventricular remodeling.
In patients with symptomatic HFrEF and LBBB on guideline-directed medical therapy,
cardiac resynchronization therapy is indicated to reduce morbidity and mortality.
Other forms of electrical instability, including atrial fibrillation with inadequate rate control
and frequent premature ventricular complexes, can also contribute to worsening HF.
In addition to the direct impact of tachycardia and irregular rhythm on disease progression,
the link between these arrhythmias and cardiac remodeling (atrial and ventricular) involves
increased wall stress, neurohormonal activation, and inflammation.

25. Secondary mitral regurgitation
A large number of patients with HFrEF demonstrate evidence of mitral regurgitation.
This occurs due to a distortion in the mitral valve apparatus and includes the effects of various
pathophysiologic mechanisms including reduced contractile force, which leads to decreased
coaptation of the leaflets, a spherical shape of the ventricle that influences length and function
of the chordal-papillary muscle structure, increased dimension of the mitral annulus (and
inability of the annulus to contract during systole) with reduced leaflet alignment, and
dilation of the posterior wall of the left atrium, which distorts the posterior leaflet of the valve.
This worsening in regurgitant volume contributes to progression in HF and adversely
influences prognosis.
Ensuring that this vicious cycle is interrupted is now a therapeutic target in HF.
Some success has been noted by treating the mitral valve using transcatheter techniques when
patients are carefully selected after exposure to optimal medical therapy when residual and
significant secondary mitral regurgitation persists

26. CARDIORENAL SYNDROME
The heart and kidney interaction increases circulating volume, worsens symptoms
of HF, and results in disease progression, referred to as the cardiorenal syndrome.
Traditionally, this relationship was deemed to be a consequence of an impairment in
forward flow (cardiac output) leading to a decrease in renal arterial perfusion, worsening
renal function, and neurohormonal activation with release of arginine vasopressin,
resulting in water and sodium retention.
However, evidence has emerged that renal dysfunction may not be adequately explained
simply by arterial underfilling and a decline in cardiac output.
Systemic venous congestion in HF with increased backward pressure may be
operative in determining the development of the cardiorenal syndrome, and relief of
venous congestion is associated with significant improvement in renal function in HF.
Increased intraabdominal pressure, as noted in right-sided HF, and a rise in abdominal
congestion are correlated with renal dysfunction in worsening HF.

28. Reference :

Verma D, Firoz A, Garlapati S, et al.
(August 17, 2021) Emerging Treatments
of Cardiorenal Syndrome: An Update on
Pathophysiology and Management.
Cureus 13(8): e17240.
doi:10.7759/cureus.17240

31. The interaction is not only confined to the renal component of the abdominal compartment
but also involves the liver and spleen.
The splanchnic veins serve as a blood reservoir and actively function in regulation of
cardiac preload during changes in volume status, regulated by transmural pressure changes
or mechanisms of systemic sympathetic activation.
The liver and spleen participate in determining volume regulation in HF in addition to several
additional interactive pathways.
Splanchnic congestion results in portal vein distension and activation of the hepatorenal
reflex as well as the splenorenal reflex, which induces renal vasoconstriction.
Thus, decongestion in HF by diuretic therapy or mechanical means such as ultrafiltration
reduces volume, but also facilitates a decrease in pressure within the abdominal compartment,
and this combination of therapeutic effect may serve to improve renal function in HF.

32. Reference : Goffredo G, Barone R, Di Terlizzi V, Correale M, Brunetti ND, Iacoviello M. Biomarkers in Cardiorenal
Syndrome. J Clin Med. 2021 Jul 31;10(15):3433. doi: 10.3390/jcm10153433. PMID: 34362216; PMCID: PMC8348334.

33. Reference : Goffredo G, Barone R, Di Terlizzi V, Correale M, Brunetti ND, Iacoviello M. Biomarkers in Cardiorenal
Syndrome. J Clin Med. 2021 Jul 31;10(15):3433. doi: 10.3390/jcm10153433. PMID: 34362216; PMCID: PMC8348334.

34. Gut congestion , microbiome and inflammation
The circulating levels of proinflammatory cytokines are elevated in a number of
cardiovascular disease states, including HF, and have been associated with disease
progression.
While the primary source of inflammation is unknown, emerging evidence suggests
that an alteration in gut microbial composition and loss of microbial diversity may
play an important role.
The potential role of gut congestion and also altered gut microbial composition may
propagate the chronic state of inflammation and immune system dysregulation,
eventually leading to progression of HFrEF.

35. Lipopolysaccharide (LPS) is a gram-negative bacterial cell wall product whose levels are
increased in patients with HF and increased intestinal permeability during periods of
congestion, and reduced with diuretic treatment.
LPS is a strong stimulator of the immune system and can lead to dysregulated systemic
inflammation via macrophage activation. Resulting increases in cytokines such as TNF-α,
IL-1, and IL-6 in these pathways can cause progressive loss of cardiac function and also
contribute to cardiac cachexia.
A mechanistic link has been shown between gut microbe–dependent generation of
trimethylamine N-oxide derived from specific dietary nutrients such as choline and carnitine
and poor outcomes in patients with both acute and chronic HF.
Microbe-generated uremic toxins, such as indoxyl sulfate, may play an important role in the
development of HF, particularly in interaction with renal insufficiency.
Thus, bowel ischemia and/or congestion depending on HF severity may be associated with
morphologic and functional alterations in the intestines and result in bacterial endotoxemia
and a proinflammatory state.

36. EVALUATION OF A PATIENT WITH HEART
FAILURE

38. Initial assessment of patients presenting with heart failure.

The initial evaluation starts with a thorough history and physical examination, focusing on detection of
comorbidities including hypertension, diabetes, and dyslipidemia. In addition, identification of valvular heart
disease, vascular disease, history of mediastinal radiation, or exposure to cardiotoxins (e.g.,
chemotherapy, alcohol, or illicit drugs) may help determine underlying cause. A family history of sudden
death, heart failure, arrhythmias, or cardiomyopathy is also useful.

Routine laboratory evaluation should also be performed. Chest x-ray is useful to detect cardiomegaly and
fluid overload and to rule out pulmonary disease. A 12-lead electrocardiogram should be performed to
detect abnormalities of cardiac rhythm and conduction, left ventricular hypertrophy, and evidence of
myocardial ischemia or infarction. Two-dimensional echocardiography with Doppler imaging is indicated to
assess cardiovascular structure and function and detect abnormalities of the myocardium, heart valves, or
pericardium. Further imaging and laboratory studies aimed at identifying a specific cause of
cardiomyopathy depend on information obtained from the history and physical examination.

In all patients, risk stratification should be performed to assess severity of illness, guide therapy, and
provide prognosis to patient and family.

CMR, cardiac magnetic resonance imaging; CT, computed tomography; NYHA, New York Heart
Association; PET, positron emission tomography

39. NYHA class does not correlate well with other objective measures of cardiac structure (e.g., left
ventricular size, EF) or function (e.g., peak oxygen consumption).

42. REFERENCE
1.Harrison’s Principles of Internal Medicine 21st
edition

2.2022 AHA/ACC/HFSA Guideline for the
Management of Heart Failure