Heart Failure

HF is associated with high mortality and morbidity.

There are approximately 6 million patients currently affected by heart failure.

It is the second most common cause of hospitalization among adults.

End stage heart failure kills more than 300,000 Americans each year.

Affects approximately 64 million people worldwide.

Its  prevalence is increasing in many middle and low income countries.

The average in-hospital mortality for heart failure is 3%, and unplanned readmissions within 30 days of discharge occur in more than 20% of patients.

Approximately 80% of all heart failure admissions occur in individuals over the age of 80.

Overall prevalence 6.5 million people in US with 1,000,000 new cases each year.

Accounts for more than 1 million primary, and 2 million secondary hospitalizations in the US per year.

Lifetime risk of 20-45% between ages 45 and 95 years.

2.7% of patients with heart failure have type two myocardial infarction.

The 30 day risk of readmission and 30 day mortality associated with heart failure have not decreased substantially over time.

Patients with heart failure with type two myocardial infarction have higher in hospital mortality and resource utilization.

Patients with heart failure with type two myocardial infarction have higher rates of 30 day all cause readmission.

Patients with type two myocardial infarction assocociated HF are more likely to be males with a distinct profile of underlying comorbidities.

Estimated annual cost of $31 billion in the US.

Associated with about a 50% mortality at five years after diagnosis.

About 50% of patients have heart failure with reduced ejection fraction (HFrEF).

As the population ages the overall prevalence of patients with heart failure and a preserved ejection fraction is increasing.

Heart failure with preservedejection fraction is associated with substantial functional and quality of life impairments that are at least equivalent to those of patients with heart failure and a reduced ejection fraction.

Exertional intolerance is a cardinal manifestation of heart failure with reduced left ventricular ejection fraction.

The disease burden has increasingly shifted from high income countries to low and middle income countries due to population growth, aging, and increased prevalence of heart failure risk factors.

Acute decompensated heart failure accounts for more than 1 million hospitalizations in the US each year.

When developed, heart failure results in a one-year mortality rate of 7.2% and a one year hospitalization rate of 31.9% in patients with chronic heart failure, and patients hospitalized for acute heart failure, these rates increased to 17.4% and 43.9%.

Rates of short term unplanned re-hospitalization and death associated with acute decompensated heart failure or high, 21% and 12%, respectively.

Patients with heart failure with reduced ejection fraction from low and middle income countries experience a higher one-year mortality rate in those in high income countries despite being almost one decade younger.

1 in 4 middle aged adults will develop HF if they survive to 85 years.

Contributes to 1 in 9 deaths.

After being hospitalized for heart failure, approximately one in four patients are readmitted within 30 days of discharge.

22-37.4% of the one and a half-2,000,000 persons living in a skilled nursing facility have heart failure.

As a result of insufficient cardiac output to provide adequate blood flow to meet metabolic and circulatory demands.

A syndrome of exercise intolerance that results from an abnormal elevation in left ventricular filling pressure.

Develops because of systolic or diastolic cardiac function, and its causes are heterogeneous.

Frequently associated with increased left atrial pressure and left atrial chamber size.

Causes neurohormonal pathways to be up regulated, including sympathetic nervous system, renin-angiotensin-aldosterone system, and vasopressin axis.

Temporarily mean arterial lay pressure and cardiac output increase to adequate levels for tissue perfusion, however chronic neurohormonal activation leads to salt and water retention and worsening of cardiac failure.

Among patients having elective non-cardiac surgery, heart failure with or without symptoms is significantly associated with 90 day postoperative mortality (Lerman BJ).

Organizing heart failure into either reduced or preserved left ventricular systolic function allows the ability to understand underlying mechanisms of disease, prognosis, and response to certain treatments.

HFrEF is defined as the presence of signs and symptoms of heart failure with the left ventricular ejection fraction of 40% or less.

Heart failure with preserved ejection fraction-HFpEF is defined as clinical signs and symptoms of heart failure with LVEF 50% or greater.

Prevalence to increase 25% by 2030.

Almost 22% of elderly with heart failure are admitted to the hospital in the month after discharge.

Approximately 2% of Americans have heart failure and 35% cardiovascular deaths directly related to heart failure.

Causes about 300,000 deaths annually in the United States.

Lifetime risk about 20-45% among various groups.

Prevalence in Medicare patients has an annual age -adjusted incidence rate of 29 cases per 1000 person-years.

Costs approximately $32 billion annually.

80% of her heart failure costs are due to hospitalizations and readmissions.

For individuals older than 65 years of age, is the most common diagnosis at hospital discharge in the primary cause of readmission within 60 days of leaving the hospital.

About 20% of Medicare patients discharged from the hospital, where re-hospitalized within 30 daysand that number rose to 34% within 90 days with the majority of these hospitalizations for heart failure.

The risk of heart failure increases sharply with increasing age, with rates doubling every 10 years among older adults.

Estimated that 1 in every 5 adults aged 40 years of age will develop heart failure during their remaining lifetime (Lloyd-Jones).

Primarily a disease of the elderly, with prevalence increasing from 0.9% in patients age 55-64 years to 17.4% in individuals over the age of 85 years.

The five year risk of heart failure among 40-year-old white people is only 0.1-0.2%.

Annual incidence approximately 10 per 1000 patients 65 years and older, with men and women affected equally.

Women are more likely to develop HF at an older age than men.

The etiology of heart failure in women is less likely be ischemic and more likely to occur in the setting of preserved left ejection fraction.


Heart failure affects 10% of adults aged 65 years and older, and more women than men in absolute numbers.


Heart failure occurs at an older age and with less ischemic causes in women than in men. 


Hypertension and diabetes predispose older women to heart failure to a greater extent than men. 


Heart failure with preserved ejection fraction, a form of heart failure with normal systolic function, is twice as prevalent in women as in men. 


Heart failure with reduced ejection fraction affects more men than women. 

Decrease muscle sympathetic nerve activity is the hallmark, and it is an independent marker of mortality.

Sympathetic hyperactivity Is a major contributing factor to skeletal muscle wasting in heart failure.

Muscle wasting is associated with a negative response to drug treatment, poor quality of life, and mortality.

Women have a higher survival rate with HF then men, but readmission rates are similar for men and women.

Approximately 20% of patients newly diagnosed die within one year.

In hospital mortality and 60-90 day mortality for heart failure are 8% and 13%, respectively.

Active smoking in a population of patients with HF is associated with more than 40% increase in mortality compared to patients with HF who have never smoked.

Death, myocardial infarction, recurrent hospitalization for patients with HF is significantly greater in current smokers, or those who no longer smoke, with a relative risk 1.39 (Suskin N et al).

Smoking cessation in HF patients accruse benefits rapidly, so that within two years of quitting smoking risk improves to the level of those who have never smoked.

Up to 50% of patients may go unrecognized.

Acute heart failure syndromes (AHFS) defined as new-onset or recurrent or worsening signs and symptoms of HF necessitating urgent or emergency management.

Acute heart failure has obvious triggering events such as physical activity and other stress-inducing behaviors prior to clinical deterioration, in about 50% of patients.

Acute heart failure syndrome patients experienced significant improvement during hospitalizations, the postdischarge re-hospitalizations great and mortality within 60-90 days remains as high as 30% and 15%, respectively (Gheorghiade M et al).

Three phases of acute heart failure syndromes proposed: 1, urgent treatment and stabilization, often in the emergency department, 2 in-hospital management, 3 postdischarge vulnerable period (Gheor M et al).

Mortality after onset ranges from 20-50%.

A prominent abnormality in HF is defective handling of calcium ions by the cardiomyocytes.

Almost 1/3 of all heart failure patients suffer from hypocalcemia and an associated poor prognosis.

Substance abuse is common among patients with heart failure: methamphetamine abuse, alcohol abuse, opioid abuse and cocaine are associated with hospital encounters and readmission for heart failure.

Action potential in the heart increases the level of intracellular calcium by two mechanisms, firstly, extracellular calcium enters the cell through L-type calcium channels increasing intracellular calcium concentration, which leads to type 2 ryanodine receptor opening and release of calcium from the sarcoplasmic reticulum.

Secondly, reversal of these changes occurs during cardiac relaxation i.e. diastole, with the removal of calcium to the extracellular space with the extrusion of calcium through the sodium-calcium exchanger and re-uptake of calcium into the sarcoplasmic reticulum through ryanodine receptor 2 closing and the through activation of isoform 2a of sarcoendoplasmic reticulum calcium ATPase (SERCA2a).

Usually associated with left ventricular dysfunction.

Patients with left ventricular ejection fraction of 40% or less are considered to have heart failure with reduced ejection fraction or systolic heart failure.

In patients with left ventricular ejection fraction of 50% or greater and symptoms of heart failure are considered to have heart failure with preserved ejection fraction or diastolic heart failure, and there is little evidence that drug treatment improves clinical outcome in these patients.

When faults exist in the above mechanisms abnormalities in systole and diastole exist leading to HF and increased risk of cardiac ventricular arrhythmias.

Annual mortality rates varies from 15% for unselected patients, to as high as 50% in patients with New York heart Association (NYHA) class IV heart failure, or who have symptoms even at rest.

Sudden cardiac death occurs 6-9 times the rate of the general population.

Heart failure affects men and women in near-equal numbers, but not all treatments are effective in improving outcomes in men have also proven effective in women.

Patients with CHF with more signs of congestion-jugular venous distention, Edema, lung rales, and S3 gallops are at higher risk of cardiovascular death or heart failure hospitalization independent of symptoms, natriuretic peptides, and validated risk scores.

Approximately 80% of men and 70% of women younger than 65 years die within 8 years of diagnosis.

Deficiency in anabolic hormones is associated with increased morbidity and mortality in male patients with heart failure.

Low circulating testosterone levels affects around 20-30% of male patients with heart failure, related to higher neurohormonal activation, skeletal muscle wasting, and lower functional capacity.

In the US, blacks have a higher prevalence of heart failure than individuals of other races, and they present with symptoms at younger ages.

The higher incidence among blacks is related to the risk of hypertension, a genetic predisposition to cardiomyopathy, and exposures to toxins including drugs and alcohol.

Arterial hypertension is the most common cause predisposing to HF, and Is independent of the occurrence of coronary artery disease.

The incidence of HF in hypertension is as frequent as that of stroke.

Antihypertensive treatments reduce the incidence of heart failure.

Patient with heart failure have decreased renal perfusion, which activates the sympathetic and renin-angiotensin-aldosterone system (RAAS) and leads to the vicious cycle of water and salt retention despite the fluid overload.

The natriuretic System is impaired early and heart failure along with inappropriate levels of vasopressin together causing for the salt retention.

Evidence for recommending dietary sodium restriction in patients with heart failure is sub optimal, and there is no consensus on the optimal level of sodium intake.

Scientific evidence fails to demonstrate the value of a very low sodium diet, a high sodium diet however is not in the patient’s best interest.

The above problems provide a basis for a low sodium diet in all patients with heart failure.

A meta-analysis indicates that iron therapy can reduce heart failure hospitalization, increase cardiac function, improve quality-of-life, decreased serum levels of BNP and CRP in patients with heart failure (ZhouX).

Patients with heart failure both of preserved and reduced ejection fraction have altered structure and function of the gastrointestinal mucosa as a consequence of micro circulatory disturbances with a leaky intestinal barrier, and augmented bacterial biofilm all of which may contribute to chronic inflammation and malnutrition.

This lack of mucosal integrity, with local and systemic inflammation and dysfunction of transport proteins could help worsen heart failure and its symptoms.

CA125 is a marker of congestion in patients with acute heart failure.

Compared to usual care, CA 125-guided therapy is associated with marked reduction in the endpoint of one-year death  or acute heart failure-related readmission in acute heart failure.

A CA 125 guided diuretic strategy improves glomerular filtration rate and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction ( Nunez J).


Iron deficiency is clinically a relevant comorbidity inup to 50% of patients with heart failure and is associated with the severity of the disease.

Anti-hypertensive treatments with calcium channel blockers are less effective than renin-angiotensin system inhibitors in reducing HF development.

Chronic kidney disease is a strong predictor and black men are disproportionately effected by declining kidney function in young adulthood.

Cytokines TNF and IL-6 are increased with HF and associated with worse survival.

CARDIA study revealed that in the young blacks in whom heart failure subsequently developed were more likely than those in whom it did not develop to have systolic dysfunction, LVH in young adulthood, 10 years prior to the onset of clinical heart failure.

Acute heart failure syndrome patients may present insidiously or acutely with symptoms ranging from mild dyspnea to extremis with acute pulmonary edema or cardiogenic shock.

Severity of presentation with acute heart failure syndromes does not correlate well with long-term prognosis, such that patients presenting with pulmonary edema due to severe hypertension and normal systolic function may have an It excellent prognosis, and patients with moderate dyspnea and severe left ventricular dysfunction may have high mortality.

Acute CHF patients with renal impairment treated with low dose dopamine or low dose nesiritide did not improve congestion or renal function (The ROSE Acute Heart Failure Randomized Trial).

Dyspnea, the most common symptom of acute heart failure syndrome, is evaluated by clinical history and five or seven Likert scale, and supplemented by evidence of jugular venous distention, peripheral edema, rales, and x-ray evidence of pulmonary congestion (Gheorghiade M et al).

Most patients with acute heart failure syndrome and dyspnea respond to intravenous diuretics, while some patients require intravenous vasodilators such as nitroglycerin, and rarely invasive mechanical ventilation and mechanical support would ensure a lead balloon pump are needed.

In the management of acute heart failure syndromes intravenous inotropic agents except digoxin, and should be avoided if possible.

Acute disease associated with dyspnea caused by increased pulmonary capillary wedge pressure, frequently associated with decreased stroke volume, cardiac index and increased vascular resistance.

Leading cause of hospitalization in individuals over the age of 65 years, with more than 3.6 million admissions with heart failure as the primary or secondary discharge diagnosis each year.

Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and Beta-adrenoreceptor antagonists reduce the mortality and morbidity of this process.

Regular exercise training in patients with systolic heart failure is safe and produced nonsignificant reduction in the primary end point of all cause mortality or all cause hospitalization and in key secondary clinical end points (HF-ACTION).

In a study 5115 black and white individuals of both sexes from ages 18 through 30 at baseline, followed over 20 years- 27 participants developed heart failure: all patients but one was black-incidence of heart failure before age 50 is substantially more common among blacks than whites and hypertension, obesity and systolic dysfunction present before age 35 years of age are important antecedents (CARDIA).

CARDIA study indicated that heart failure developed before the age of 50 years in one of 100 Black men and black women, our rate 20 times the incidence and whites.

The incidence of heart failure in blacks is up to two times as high as in whites in the elderly population.

Each increase 10 mm Hg of diastolic blood pressure in blacks in their 20s, doubled the likelihood that heart failure would develop when they were in their 40s (CARDIA)

Obesity contributes to the risk either directly or through the Association of increased blood pressure and the development of type II diabetes.

Heart failure and type two diabetes are linked.

When heart failure develops in patients with type two diabetes it is complicated by markedly higher rates of mortality.

There is a graded increase in the risk of heart failure as BMI increases: for every 1 kg per meter squared increase in BMI the risk of heart failure increases 5% in men and 7% in women (Kenchaiah S et al).

Obesity has profound effects on systolic and diastolic function.

Obesity is a major risk factor for heart failure, particularly for heart failure with preserved ejection fraction.

Obesity paradox, refers to the suggestion that obese patients with heart failure have a better prognosis than leaner patients (Lavie CJ et al, Arthram SM et al).

Individuals with an elevated BMI, compared to individuals without an elevated BMI and heart failure,have a reduction in cardiovascular and all cause mortality during a 2.7 year follow-up (Oreopoulos A et al).

In an in-hospital mortality study of 108,927 patients would be compensated heart failure, a higher BMI was associated with a lower mortality: a 10% lower mortality was noted for every five unit increase in BMI (Fonarow GC et al).

In the CARDIA study increased body mass index was an early independent risk factor for heart failure with diabetes an confounding or more likely mediating this association.

Chronic kidney disease is a strong predictor and black men are disproportionately effected by declining kidney function in young adulthood.

CARDIA study revealed that in the young blacks in whom heart failure subsequently developed were more likely than those in whom it did not develop to have systolic dysfunction, LVH in young adulthood, 10 years prior to the onset of clinical heart failure.

HIghly sensitive cardiac troponin T assay is detected in almost all patients with heart failure or ischemic heart disease.

In a longitudinal study of 4221 community dwelling adults age 65 years or older without prior heart failure using a highly sensitive cardiac troponin T assay at baseline and repeated after 2-3 years changes were significantly associated with the incident heart failure and cardiovascular deaths (de Filippi CR et al).

The standard of care consists of decongestion with intravenous diuretics and hemodynamic support with vasodilators and inotropes, which has remained largely unchanged during the past 45 years.

Patients with heart failure with reduced ejection fraction and should take both an angiotensin-converting enzyme inhibitor and the beta blocker, and if volume overloaded, a diuretic as well.

In the above setting an angiotensin receptor blocker is recommended for patients who cannot tolerate an ACE inhibitor.

The addition of an aldosterone antagonist can reduce mortality and hospitalization in patients with symptomatic heart failure or with left ventricle dysfunction after a myocardial infarction.

The addition of hydralazine and isosorbide dinitrate to standard treatment reduces mortality and symptoms in black patients with NYHA class 3-4 heart failure was reduced ejection fraction.

Digoxin can decrease symptoms and lower the rate of hospitalization for heart failure patients but does not reduce mortality.

In the Digitalis Investigative Group trial digoxin reduce the risk of hospitalization for all causes and heart failure in patients who were ambulatory with chronic heart failure with left ventricular ejection fraction of 45% or less.

Among hospitalized patients with heart failure with reduced ejection fraction digoxin was associated with the lower risk of hospital readmission but not all-cause mortality. (Quaker SC).

For the management of NYHA class III heart failure home transmission of pulmonary artery pressures within implanted pressure sensor significantly provides long-term benefit in lowering hospital admission rates for heart failure CHAMPION Trial).

The iniation of sacubitril-valsartran therapy has led to a greater reduction in the NT-pro BNP concentration than in the enlapril therapy.

Empagliflozinuse among patients with heart failure had a lower risk of cardiovascular death or hospitalization than in the placebo group, regardless of the presence or absence of diabetes. (Packer M).

In a randomized trial that included 5647 patients with heart failure, randomized quality improvement intervention compared with usual care had a rate of re-hospitalization that was not statistically significant (DeVoreA).

Evidence exists that the gut microbiome affects the development of cardiovascular disease, and heart failure in particular.

Elevated levels of phenylacetylglutamine (PAG), a byproduct created when microbes in the gut break down dietary protein, is linked to increased heart failure risk and severity. 

Studies show linked increased PAG levels to a higher risk of myocardial infarction (MI), stroke, and death.

A microbiome that is predisposed towards making PAG is at higher risk of cardiovascular disease, especially heart failure.


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