CHF secondary to systolic dysfunction is the result of an impaired inotropic state.

Heart failure with reduced ejection fraction (HFrEF), affects more than an estimated 3 million people in the US.

About 50% of heart failure hospitalizations are for heart failure with reduced ejection fraction come with the balance caused by heart failure with mid range or preserved ejection fraction.

Causes include idiopathic dilated cardiomyopathy, or myocardial infarctions that damage the muscle.

The major causes of systolic heart failure are coronary artery disease, hypertension, cardiomyopathy, valvulopathies and myocarditis.

Predictors of incident HFrEF include older age, male sex, higher heart rate, hypertension, coronary artery disease, previous myocardial infarction, diabetes, and valvular heart disease.

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.

Men are more likely to have heart failure with a reduced ejection fraction than women.

SHF is predictable by 2-D echocardiogram with a reduction of left ventricular ejection fraction.

Reduction in left ventricular ejection fraction is associated with alteration in the intracardiac geometry and hemodynamics.

Patients are examined for markers of congestion and reduced peripheral perfusion.

Because of compensatory regulation in lymphatic drainage, patients with chronic HFrEF at lack lung rales or peripheral edema even when pulmonary capillary wedge pressure is elevated.

In patients with left ventricular ejection fraction of 40% or lower, trials have demonstrated the benefits of inhibitors of the renin-angiotensin system, sympathetic nervous system, aldosterone, and neprilysin reducing the risk of cardiovascular death and hospitalization for heart failure.

Patients with heart failure and a LVEF of 40-50% have similar clinical features as those with a LVEF lower than 40%.

Increasing contractility by stimulation with drugs has consistently failed to improve outcomes and often resulted in increased mortality.

Drugs that have a negative affect on contractility such as angiotensin converting enzyme inhibitors and data adrenergic receptor blockers have been shown to improve outcomes.

The harmful effect of inotropic agents is related to the mechanism of action, the stimulation of contractility through modulation of myocardial cyclic AMP resulting in increased mortality risk due to provocation of ventricular arrhythmias and acceleration of worsening ventricular dysfunction, despite favorable hemodynamic effects.

Positive inotropic agents,cardiac myosin activators, increase the coupling between myocardial actin and myosin without increasing myocardial oxygen consumption prolonging systolic ejection time.

CHARM-Preserved trial evaluated the effects of an angiotensin receptor blocker candesartan in patients with heart failure and LVEF higher than 40%: compared with placebo candesartan reduced the risk of cardiovascular death or hospitalization for heart failure in patients with LVEF for 40-49%, but not in patients with LVEF higher than 50% or higher.

Systolic HF contributes to a hypercoaguable state because of reduced cardiac output, peripheral edema, reduced exercise, increased platelet activitity, and increased coagulation factors.

Typical symptoms of HFrEF include dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and ankle swelling.

Coronary micro vascular inflammation leads to high diastolic left ventricular stiffness and heart failure with preserved ejection fraction by suppressing unfolded protein response in cardiomyocytes owing to the expression of inducible nitric oxide synthetase.

This suppression hinderss adequate cellular degradation of the stabilize proteins and can lead to their interstitial accumulation.

Microvascular inflammation is accompanied by increased adhesion molecules on the luminal surface of the cells and they snag circulating monocytes which then differentiate into macrophages as they infiltrate the microvascular and secrete transforming growth factor beta.

Micro vascular inflammation uncouples endothelial nitric oxide synthase, leading to lower levels of nitric oxide and higher levels of reactive oxygen species, which are toxic.

The lower levels of nitric oxide in cardiomyocytes lead to diminished phosphorylation of Titin and cardiomyocyte elasticity.

Elevated plasma levels of pro inflammatory cytokines boost expression of inducible nitric oxide synthase in cardiac myocytes resulting in reduced activity of proteins that control the unfolded protein response.

Titins effect on reactive oxygen species reduces myocyte distensibility.

Transforming growth factor bets turns fibroblasts into myofibroblasts that deposit collagen with high tensile strength.

Other symptoms of right heart failure may be present that include abdominal bloating, right upper quadrant discomfort, and early satiety.

Bendopnea, shortness of breath when leaning forward, is also suggestive of heart failure.

Reduced EF increases risk of formation of left ventricular thrombus.

Systolic HF associated with increased risk of stroke of 1.2-1.8% per year, and systemic embolism 1.5-2.7% per year.

With SHF the lifelong ellipsoid shape of the left ventricle is distorted by a greater increase in the short axis than the long axis resulting in an increase of sphericity defined as the ratio of the left ventricle short axis diameter to the left ventricular long axis length.

Control of hypertension and minimizing ischemia are important goals.

The addition of a mineralcorticoid receptor antagonist (Spironolactone) to patients with heart failure and left ventricular ejection fraction of 35% who are already onan ACE inhibitor or angiotensin receptor blocker and the beta blocker who meet renal eligibility criteria for therapy should receive such treatment.

Medical therapy treatments for heart failure with reduced ejection fraction consist of beta blockers, renin-angiotensin system blockers with neprilysin inhibitors, mineralocorticoid receptor antagonists and SGLT2 inhibitors, in addition to diuretics: which reduce mortality among patients with HFREF by estimated 63% versus placebo.

Most calcium channel blockers, excluding amlopidine, are associated with no benefit at best and increased mortality at worst in patients with heart failure with reduced ejection fracture.

Th addition of a sodium glucose code transporter2 (SGLT 2) Inhibitors reduce risk by a further 2.3%

In older patients with heart failure with reduced ejection fraction eligible for mineralocorticoid receptor antagonist therapy, the use of Spirinolactone was associated with an 8-13% lower risk of all cause mortality, heart failure, hospital readmission,.

ACE inhibitors and Angiotensin Receptor Blocking agents appear to be indicated for both systolic and diastolic heart failure.

ACE inhibitors are recommended in all patients with heart failure with reduced ejection fraction (HFreEF) to reduce morbidity and mortality.

TOPCAT Trial evaluating the effects of Spironolactone with LVEF of 45% or higher: the drug reduced the risk of cardiovascular death in hospitalization for heart failure but was beneficial only to patients with LVEF lower than 50%.

PARAGON-HF trial evaluated Sacubitril-valsatran in patients with heart failure and LVEF a 45% or higher: The hazard ratio for patients with LVEF at 57% or lower was 0.78.

Digoxin might be considered in systolic dysfunction, mainly now when there is atrial fibrillation.

Among individuals with heart failure with reduced ejection fraction, atrial fibrillation coexist in greater than 50% of patients and is associated with increased mobility and mortality.

((Vericiguat)) In patients with heart failure reduces the incidence of death from cardiovascular causes or hospitalization for heart failure.

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).

Among patients with severe ischemic left ventricular systolic dysfunction who receive optimal medical therapy, PCI revascularization does not result in a lower incidence of death from any cause or hospitalization for heart failure.

In the above trial patients with severe left ventricular systolic dysfunction, extensive coronary disease, and dysfunctional but viable myocardium who received optimal medical therapy, addition of revascularization by PCI did not result in lower incidence of death from any cause or hospitalization for heart failure, incremental improvement in left ventricular ejection fraction, or a sustained difference in quality of life and a median of 3.4 years.

In the Surgical Treatment for Ischemic Heart Failure trial the incidence of death from any cause at five years was similar in a group undergoing CABG and a group assigned to receive medical therapy alone: survival benefit emerged over time with patient undergoing revascularization with CABG more likely to be alive after 10 years and those receiving medical therapy alone.

Cardiac resynchronization therapy improves functional capacity, quality of life, and survival in patients with heart failure and reduced ejection fraction.

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