Left Ventricular Function

Presentation on echocardiographic assessment of LV function

More on assessment of LV function in the subsections of the Normal echocardiography section (Apical views, Parasternal Long Axis, Parasternal Short Axis).

More information in the section related to inotropic support. 

Neonatal Left Ventricle (LV): Properties and Determinants of Function

Key Properties of the Neonatal LV

• Structural Immaturity

  • The neonatal LV has relatively less developed myocardial fibers compared to adults, with fewer contractile elements and prominent trabeculations.

  • The structure is geared towards accommodating the perinatal circulatory transition, with features such as higher wall compliance and a relatively larger cavity volume for its body size.

• Immature Calcium Handling

  • Neonatal cardiomyocytes feature an underdeveloped sarcoplasmic reticulum and reduced T-tubule density, leading to less efficient calcium release and reuptake, and a greater reliance on transsarcolemmal calcium influx.

• Transitional Circulatory Changes

  • At birth, there is a rapid shift from fetal parallel circulation (placental and ductal) to serial circulation through the LV supporting systemic flow as the ductus arteriosus closes.

  • The LV becomes the main chamber for systemic output, and its preload and afterload conditions change sharply with lung aeration and cord clamping.

• Functional Characteristics

  • Neonatal LV systolic and diastolic function are less mature, with lower compliance and less capacity to increase stroke volume under stress compared to older children and adults.

  • The ejection fraction and fractional shortening may be slightly lower compared to later life, particularly in preterm infants.

• Dynamic Adaptation

  • The LV adapts quickly in the initial days after birth, showing rapid changes in end-diastolic volume, stroke volume, and output as loading conditions evolve.

Determinants of Neonatal LV Function

• Preload

  • Initially dependent on umbilical venous return; after birth, pulmonary venous return from increased pulmonary blood flow becomes the main source of preload as the lungs expand and functional left-to-right shunting begins through the ductus arteriosus.

  • Changes in preload are key to LV performance in the immediate postnatal period.

• Afterload

  • Determined by systemic vascular resistance, which rises after birth due to cord clamping and loss of the low-resistance placental circuit.

  • The neonatal LV is less able to cope with a sudden increase in afterload, which can impair output if transition is not smooth.

• Contractility

  • Inherently lower than in older age groups, due to histological and biochemical immaturity (e.g., differences in myosin isoforms, calcium handling).

  • Susceptible to stressors such as hypoxia, sepsis, or metabolic disturbances.

• Heart Rate

  • Cardiac output in neonates relies heavily on heart rate rather than stroke volume, since their heart is operating near the top of the Frank-Starling curve (limited capacity to increase stroke volume).

• Other Factors

  • Ventilation and oxygenation status (lung aeration reduces pulmonary vascular resistance, enhancing preload).

  • Patency of shunts (ductus arteriosus and foramen ovale).

  • Myocardial metabolism and substrate availability.

Key Structural Features of the Neonatal Left Ventricle (LV) Influencing Its Function

• Myofiber Immaturity

  • Neonatal myocardial fibers are less organized and less densely packed than in older children or adults.

  • Contractile elements (myofibrils) are fewer, and there is increased prominence of non-contractile (interstitial) tissue, resulting in less contractile force and efficiency.

  • Titin is a giant, elastic protein found in striated muscle, including the myocardium. It plays a critical role in diastolic function by contributing to the passive stiffness and elastic recoil of the cardiac muscle during relaxation. Molecular weight: ~3,000–4,000 kDa — the largest known human protein. Location: Spans half the length of a sarcomere, from the Z-disc to the M-line. 

    1. Acts as a molecular spring that: 

       1. Maintains sarcomere structural integrity. 

       2. Restores sarcomere length after contraction. 

       3. Modulates passive tension during diastole.

• Higher Wall Compliance

  • The LV wall is more compliant (less stiff) in neonates, allowing for easier filling at low pressures but limiting the chamber’s ability to increase pressure during contraction.

  • This higher compliance means the ventricle is susceptible to volume overload but less able to compensate for increased afterload.

• Larger Relative Cavity Size

  • The LV cavity is relatively larger compared to wall thickness in neonates, enabling accommodation of higher preload but at the expense of contractile power.

• Prominent Trabeculations

  • Neonatal LVs feature more prominent endocardial trabeculae (muscular ridges inside the chamber), a remnant of fetal cardiac development.

  • These trabeculations impact chamber compliance, contraction patterns, and intracavitary flow.

• Incomplete Structural Maturation

  • The LV lacks the fully developed laminar (layered) structure seen in adult myocardium, leading to differences in contraction mechanics and functional reserve.

• Underdeveloped Supporting Structures

  • The extracellular matrix and connective tissue scaffolding are immature, reducing ventricular stiffness and resilience against pressure loads.

• Stroke work increased oxygen consumption. Coronary perfusion is essential for appropriate delivery of perfusion to the myocardium. Coronary perfusion is during diastolic portion of the cardiac cycle which may be impacted by diastolic steal, low diastolic pressure, increased right atrial pressure (coronary sinus drains in the right atrium), increased heart rate (which decreases diastolic time).

• Calcium Handling Apparatus

  • Structurally, the sarcoplasmic reticulum and T-tubule system are underdeveloped, impacting calcium cycling and, therefore, contractility and relaxation.

These features make the neonatal LV particularly reliant on heart rate (rather than contractility or stroke volume) for maintaining cardiac output and limit its adaptive response to stressors such as increased afterload or volume. The chamber’s compliance and immaturity in both the myocyte structure and extracellular framework are fundamental determinants of its unique function in early postnatal life.

Neonatal Myocardium: Calcium Handling and Maturation

1. Immature Calcium Homeostasis
Neonatal cardiomyocytes exhibit structural and functional immaturity compared to adult myocytes, particularly in calcium cycling mechanisms:

• Underdeveloped sarcoplasmic reticulum (SR) and sparse T-tubule network result in:

  • Reduced efficiency of calcium release and reuptake from the SR.

  • Increased dependence on transsarcolemmal calcium influx through L-type Ca²⁺ channels during each action potential.

2. Calcium Entry and Removal Mechanisms

• Calcium Influx: Primarily occurs via L-type calcium channels (ICa,L) during membrane depolarization.

• Calcium-Induced Calcium Release (CICR): Still mediated by ryanodine receptors (RyR) on the SR, but less robust than in mature cardiomyocytes.

• Calcium Extrusion:

  • Heavily reliant on the Na⁺/Ca²⁺ exchanger (NCX) and sarcolemmal Ca²⁺-ATPase.

  • The SR Ca²⁺-ATPase (SERCA2a) is present but functionally immature, limiting SR calcium reuptake.

Classification of left ventricular systolic function

Evaluation of Left Ventricular Function

• Ejection Fraction: The percentage of blood ejected from end-diastole to end-systole.

  • Methods: Can be calculated in apical four-chamber or two-chamber views, most often using the modified Simpson's biplane method for a comprehensive view.

  • 3D Echocardiography: The most comprehensive and best form of EF measurement, allowing precise volumetric measurements (end-diastolic, end-systolic volumes).

  • Normal Range: Typically 55% and upward, though many clinicians believe infants and neonates should have a higher EF.

• Shortening Fraction: The original method for measuring LV strength and quality.

• Newer Evaluations:

  • Speckle Tracking and Strain Measurement (Global Longitudinal Strain): Deformation tracking that has advanced significantly. It provides a parabellometric map showing regionality (e.g., septum vs. lateral wall, apex vs. base) and an overall global sense of heart motion. Normal values are typically between -18 and -30.

  • Tissue Doppler at the Mitral Valve: Offers insights into diastolic and systolic function.

  • Myocardial Performance Index (MPI) or Tei Index.

  • Myocardial Regurgitation DPDT Max: A marker of how fast blood moves backward across the mitral valve; slower movement suggests less contractility.

  • Reliability in Neonates: A caveat for many newer evaluations is that while investigated in healthy children, their reliability and normative values in neonates are still being studied.

Tissot C, Singh Y, Sekarski N. Echocardiographic Evaluation of Ventricular Function-For the Neonatologist and Pediatric Intensivist. Front Pediatr. 2018 Apr 4;6:79. doi: 10.3389/fped.2018.00079. PMID: 29670871; PMCID: PMC5893826.

This article classifies left ventricular function based on LV-EF in pediatric:

• Normal LV systolic function (EF ≥ 55%), 

• Mild LV systolic dysfunction (EF 41–55%), 

• Moderate LV systolic dysfunction (EF 31–40%),

• Severe LV systolic dysfunction (EF ≤ 30%)

• LV-EF is based on estimation of End Diastolic and End Systolic volumes of the LV. These may be estimated using various methods (link to outside great article): Simpson's Biplane Method, Simpson's Disc method only applied to one of the apical views, 5/6 Area-Length Bullet Method, 3D echocardiography using Speckle-Tracking Echocardiography, 2D estimation using Speckle-Tracking Echocardiography, Teichholz formula from linear dimensions (discouraged).

Tissot et al. also provides normal and abnormal values based on shortening fraction (SF). SF (same as fractional shortening - FS) can be obtained from the M-Mode at the tip of the mitral valve in the parasternal long or short axis view. The LV end diastolic and end systolic diameters can also be obtained from the B-Mode obtained in the same view. The use of this measurement is discouraged by the recent guidelines of the American Society of Echocardiography. Often SF less than 25% is used as a marker of frank dysfunction. 

• Normal values in pediatric: 28 and 46%. 

• Normal LV systolic function (SF 26–45%), 

• Mild LV systolic dysfunction (SF 20–25%), 

• Moderate LV systolic dysfunction (SF 15–19%), 

• Severe LV systolic dysfunction (SF ≤14%).

Caveat about shortening fraction: relies on 2 point in the LV and many guidelines recommend against its use in comprehensive evaluation of the LV considering the tendency to have dyskenesis of the LV that may not be homogenous, as well as the septal flattening often found in the context of high PVR due to the transitional period of the newborn. The American Society of Echocardiography mentions: "Fractional Shortening (use is discouraged)" - complete article here.

As per the American College of Cardiology (ACC), mostly geared at adult functional classification but applied often in pediatric: 

• Hyperdynamic left ventricle = LV-Ejection Fraction (EF) greater than 70% 

• Normal LV systolic function -= LVEF 50% to 70% (midpoint 60%) 

• Mild LV systolic dysfunction = LV-EF 40% to 49% (midpoint 45%) 

• Moderate LV systolic dysfunction = LV-EF 30% to 39% (midpoint 35%) 

• Severe LV systolic dysfunction = LV-EF less than 30%.

As per the American College of Cardiology, in adults, there is the context of heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF).

"Heart failure (HF) encompasses a broad range of left ventricular (LV) function. New treatment guidelines address the entire spectrum of HF. The classification of HF is as follows: 

• HFrEF (HF with reduced ejection fraction [EF]): LVEF ≤40%; 

• HFimpEF (HF with improved EF): Previous LVEF ≤40% and follow-up measurement of LVEF >40%; 

• HFmrEF (HF with mildly reduced EF): LVEF 41-49%; 

• HFpEF (HF with preserved EF): LVEF ≥50%."

Other methods to evaluate LV systolic function include: 

• Deformation analysis using speckle-tracking echocardiography

• dp/dT of the mitral insufficiency jet (particularly useful in the context of distorted LV architecture - such as in single LV physiology)

• Estimation of LV stroke distance by LVOT velocity time integral (VTI), or cardiac output (using LVOT-VTI, HR and LVOT diameter)

• Systolic velocities at the lateral and septal wall by tissue Doppler imaging.

• Fractional area change of the LV from the Apical view (similar to the RV-FAC, but applied to the LV (particularly useful in the context of distorted LV architecture - such as in single LV physiology).

Mechanisms of Cardiac Failure 

A critical aspect of neonatal heart failure lies in the dramatic shifts from fetal to extrauterine circulation:

• Fetal Aorta: Experiences very low resistance, with the placenta being the lowest resistance point in the circuit.

• Cardiac Output Distribution: 40% of combined ventricular cardiac output goes to the placenta.

• RV Dominance: The RV is the dominant ventricle in fetal life, handling about two-thirds of the total cardiac output. The LV is comparatively "lazy".

• Post-Birth Changes: Immediately after delivery and umbilical cord clamping, there's a rapid increase in systemic vascular resistance (SVR) and, ideally, a drop in pulmonary vascular resistance (PVR). Circulation becomes "in series," meaning the entire blood volume of cardiac output flows through both ventric. Total cardiac output also increases.

• Pressure-Volume Changes: The LV experiences a dramatic increase in volume and pressure within 1-24 hours after birth, while the RV sees a reverse trend with lower volume and pressure, reflecting lower PVR. The atria experience fewer alterations, though the left atrium undergoes more of a volume load than a pressure load.

Cardiac output is calculated as stroke volume × heart rate. Key components of stroke volume include:

• Preload: The volume of blood returning to the heart, representing the stretch or distensibility of the ventricle. For the LV, this is the right ventricular cardiac output. Factors affecting preload include volume status, obstruction (pulmonary issues, congenital heart disease), and veno-dilation/contraction.

• Afterload: The resistance the ventricle must overcome to eject blood. For the LV, this is systemic vascular resistance. Obstructions like coarctation of the aorta or aortic stenosis significantly increase LV afterload.

• Inotropy: The intrinsic contractility of the myocardium, primarily controlled by the autonomic nervous system.

The Frank-Starling curve illustrates the relationship between preload and contractile force.

• Optimal Function: The ideal position is in the middle two-thirds of the curve, where thick and thin filaments have optimal overlap to generate strong contractile force.

• Fetal Position: As a fetus, the heart operates on the lower left side of the curve, meaning thick and thin filaments are overly overlapping, limiting contractile potential.

• Post-Birth Transition: With cord clamping and hemodynamic shifts, the heart progresses towards optimal sarcomeric length, allowing for higher contractile force.

Cardiac failure can manifest through four primary mechanisms, often interpretable using Frank-Starling curves. 

1. Impaired Contractility: 

   • Characterized by a flattening of the systolic pressure-volume curve (decreased slope). 

   • Leads to ventricular dilation (increased end-diastolic volume) and a reduced ejection fraction. 

   • Examples include dilated cardiomyopathies or ventricles failing due to prolonged high afterload. 

2. Increased Afterload: 

   • The systolic pressure-volume curve shifts upwards.

   • The ventricle has to work against higher pressure, leading to an increase in end-systolic volume (more residual blood) and potentially dilation. 

   • Examples include coarctation of the aorta with closing duct or severe systemic hypertension.

3. Impaired Compliance (Diastolic Dysfunction): 

   • The diastolic pressure-volume curve shifts upwards and to the left. 

   • For a given volume, the ventricle generates a much higher filling pressure. 

   • The heart is typically not dilated, and the ejection fraction remains normal. 

   • Examples include restrictive cardiomyopathies or, in congenital contexts, a stiff RV after repair of Tetralogy of Fallot, leading to signs of right heart failure like hepatomegaly.

4. Altered Preload: 

   • The pressure-volume loop shifts to the right due to an increase in cardiac volume during diastole. 

   • The heart dilates in diastole and empties correctly, potentially increasing ejection fraction initially.

   • This is typical of shunting lesions (e.g., large left-to-right shunts) that increase volume load on a chamber.

Factors Affecting the Left Ventricle at Birth

• Increased SVR: Requires increased myocardial contractility to overcome this new afterload.

• Increased LV Preload and Stroke Volume: Due to the newly established LV-dominant circulation.

• Myocardial Cell Development: Fetal cardiomyocytes undergo hyperplasia (cell proliferation), transitioning to hypertrophy (increase in cell size) after delivery. Myocardial cells can grow 30-fold in the first few months.

• Limited Contractility Augmentation: Neonates primarily augment cardiac output through heart rate, as their intrinsic ability to increase stroke volume via inotropy is limited. This intrinsic inotropic effect develops with hypertrophy. While medications can help, intrinsic ability is limited during this hypertrophic transition.

• Maladaptive Remodeling: Overcompensation can lead to LV hypertrophy and maladaptive remodeling.

Preterm Infants

Preterm and extremely preterm infants face additional challenges:

• Structurally Different Myocardium: Their myocardium is structurally different from term infants or toddlers.

• Myocardial Fiber Orientation: Cardiac development changes throughout gestation, and torsional contraction (like wringing a dish towel) doesn't fully develop until closer to 20+ weeks. This sets preterm infants up for greater propensity towards heart failure due to improper fiber orientation.

Causes of LV Dysfunction in Newborns

Causes are categorized into transient and refractory types.

1. Transient Causes: While generally transient, their severity can lead to persistence:

• Neonatal Asphyxia and Infection: Most common, sharing a similar pathophysiological mechanism driven by acidosis, which reduces myocardial contractility. Asphyxia adds complexity with hypoxia, leading to pulmonary arterial vasoconstriction, pulmonary hypertension, and reduced pulmonary blood flow, further decreasing LV preload and output.

• Poor Transition: If the shifts in hemodynamics at birth are not managed well, it can lead to temporary ventricular dysfunction.

2. Refractory LV Dysfunction These are more likely to be persistent:

• Viral Myocarditis: The most common cause of fetal dilated cardiomyopathy, typically due to placenta-crossing agents like parvovirus, coxsackievirus, toxoplasma, HIV, and CMV.

• Metabolic Disorders: Less common, but include storage diseases, selenium deficiency, carnitine disorders, and mitochondrial disorders.

  • Metabolic Cardiomyopathy Workup: Involves genetics/metabolic team consults, plasma amino acids, urine organic acids, pyruvate levels, acylcarnitine profile, carnitine, and selenium levels.

• Maternal Autoimmune Diseases: Such as lupus or Sjögren's, which can cause mitochondrial inflammation and a myocarditis-like picture. These are more typically associated with arrhythmias or heart block.

• Genetic Causes: Particularly sarcomeric mutations (e.g., myosin-binding protein C, MYH7, Titin).

  • Left Ventricular Non-compaction: Can be isolated or associated with sarcomeric mutations, frequently seen in TAZ gene mutations like Barth syndrome.

• Fetal Arrhythmias: Tachyrhythmias (SVT, atrial flutter), bradycardias, long QT, or heart block (e.g., anti-SSA/SSB antibodies). While function should return to normal once controlled, severity and duration can lead to persistent LV dysfunction.

Treatment of Neonates with Heart Failure - Treatment approaches vary based on the acuity and persistence of dysfunction.

Acute Phase: Inotropic Medications

• Milrinone: A phosphodiesterase-3 inhibitor that increases cyclic AMP, causing a positive inotropic effect (increased myocardial contractility and stroke volume). It also has positive lusitropy effects (myocardial relaxation, improving preload) and causes vasodilation (decreased SVR and PVR). Typical dose: 0.5 mcg/kg/min (range 0.25-1.0 mcg/kg/min).

• Calcium Chloride: Particularly useful in infants and neonates because their sarcoplasmic reticulum is immature, making cardiac contraction more dependent on trans-sarcolemmal calcium influx via L-type voltage-gated channels. Increased serum calcium leads to increased myocardial contraction and improved stroke volume. It also increases SVR. 

  • Clinical Practice: Ionized calcium levels are typically monitored daily. Neonates tend to be "lenient" to calcium overload, with serious adverse events being rare. Clinicians may still give calcium as an inotropic agent even with normal or high-normal ionized calcium levels if there's a positive response. It can also be a good choice for improving blood pressure and cardiac output in hypotensive infants, even without overt LV heart failure.

• Epinephrine: A beta-1 (cardiac selective) and alpha-1 (vascular) agonist. It has positive inotropic (increased myocardial contractility, stroke volume) and chronotropic (increased heart rate, improved cardiac output) effects. However, it increases myocardial oxygen demand and workload. Typical inotropic doses: 0.02-0.05 mcg/kg/min (can go up to 0.08-0.1 mcg/kg/min before alpha-1 properties dominate).

• Potentially Harmful Vasoactives: Medications that strictly increase afterload, like norepinephrine and vasopressin, can decrease stroke volume and increase LV pressures, potentially worsening an already stressed ventricle. They should be used with caution and at minimal doses.

  • Vasopressin: While it can increase afterload, in states like septic shock with very low SVR, or pulmonary hypertension, normalizing blood pressure with vasopressin may not necessarily worsen LV afterload, unless blood pressure goes too high, or there's a direct myocardial effect independent of SBP. Some experience indicates that low diastolic pressure in LV dysfunction is not good for coronary arteries, and vasopressin can normalize this. Chronic vasopressin use (over 36-48 hours) can lead to fluid retention and hyponatremia, which can overload a failing LV. Thoughtful use is key.

• Dobutamine: Often used in NICU for mild heart dysfunction. It has chronotropic effects that can negatively impact diastolic function and coronary perfusion. While it can increase blood pressure, especially in premature patients with predominant alpha receptors, epinephrine is often favoured if the LV dysfunction is significant. It might be used as a quick option if only peripheral access is available.

Chronic Therapy

If patients stabilize on IV inotropes but haven't recovered function, transition to chronic oral therapy is considered, typically a multi-drug approach aimed at afterload reduction and sympathetic nervous system modulation.

• Afterload Reduction:

  • ACE Inhibitors: Enalapril.

  • Angiotensin Receptor Blockers (ARBs): Losartan, Valsartan.

• Beta-Blockers: To reduce heart rate and modulate the sympathetic nervous system.

  • Metoprolol: Cardiac selective, reducing pulmonary issues in patients with BPD or asthma. It allows for independent modulation of afterload reduction and heart rate compared to Carvedilol (which has alpha properties).

• Diuretics: To manage volume status in progressive heart failure.

• Spironolactone: To modulate the renin-aldosterone system.

New Horizons in Medical Therapy

• Sacubitril/Valsartan (Entresto): An ARB combined with a neprilysin inhibitor, which blocks the degradation of natriuretic peptides, leading to increased diuresis, vasodilation, and inhibition of fibrosis. FDA approved down to age 1, used off-label in infants as young as 3-6 months with severe refractory LV dysfunction.

• SGLT2 Inhibitors: Originally diabetic drugs, they were found to improve heart failure outcomes in adults, likely by modulating kidney effects to improve diuresis and the renin-aldosterone cycle. Used in patients as young as 9 months, with potential for wider pediatric use.

• Myosin Activators (e.g., Omecamtiv mecarbil): Act at the actin-myosin site to increase cross-linkages and improve contractile force. Currently approved for adults with DCM, with pediatric trials underway. Not yet used in infants and neonates.

Transition from IV to Oral Therapies

A gradual approach is used:

1. Wean higher-dose milrinone to a lower, stable dose (e.g., 0.75 to 0.5 mcg/kg/min).

2. Slowly institute an ACE inhibitor or ARB over 5-7 days while on dual therapy.

3. Once a reasonable ACE inhibitor dose is reached without hypotension, gradually wean milrinone.

4. Monitor hemodynamics and echocardiography; if LV function regresses, increase milrinone and hold for two weeks before trying again.

5. Consider optimizing beta-blockers in the chronic phase.

6. Digoxin may be used as a last-effort if avoiding VAD or transplant.

• Levosimendan: A calcium sensitizing agent. Its use is limited but there is some European litterature..

Diastolic Dysfunction

This is an incredibly challenging and nebulous entity in pediatrics and neonatology, as adult criteria are often insufficient.

• Clinical Indicators: Left atrial dilation in the absence of mitral valve regurgitation is considered a sensitive marker, suggesting elevated LV end-diastolic pressure transmitting into the atrium.

• Treatment: Unfortunately, there are limited specific treatments. Milrinone has theoretical lucotropic properties that may help. Beta-blockers can be used to blunt heart rate and allow for more diastolic filling time, thereby improving cardiac output, but this is a "band-aid" approach not addressing underlying pathophysiology.

Mechanical Circulatory Support

If medications fail, mechanical circulatory support is considered.

• XCore Berlin Pump: The only FDA-approved device for small pediatric patients, typically requiring children to be larger than 5 kg and with a body surface area (BSA) less than 0.7. It's a pneumatically driven pulsatile pump with an inflow from the LV and outflow to the aorta. It comes in various sizes (10, 15, 25, 30, 50, 60 mL).

• Newer Devices: The Jarvik pump, while still in early stages of implementation, is much smaller (paperclip/battery size), can be used down to about 2 kg.

• Threshold for Support: Generally, mechanical circulatory support is considered if:

  • The patient is maxed out on IV inotropic support.

  • Two organ systems are involved (e.g., heart with feeding intolerance, renal dysfunction, or abnormal liver enzymes).

• Early Intervention: There's a growing inclination to place devices earlier, as outcomes (pre-transplant and post-transplant survivability) are better. Avoiding ECMO (highest risk for mortality post-transplant) by using VADs leads to higher success rates after transplant.

Heart Transplant

Heart transplant is the ultimate treatment for refractory heart failure.

• Infant Outcomes: Infants have the lowest risk for rejection due to their immature immune system, leading to relative organ tolerance. They also have the longest median graft survival (about 24 years) compared to other age groups (e.g., adolescents at 15-18 years).

• Prevalence: Infants constitute one of the largest groups of pediatric patients undergoing transplant.

• Changing Diagnoses: Historically, congenital heart disease (CHD) was the primary reason for infant heart transplant (80s-early 2000s). More recently (2005-2018 data), dilated cardiomyopathy accounts for 35% of cases, and "other" (myocarditis, incessant arrhythmias) 8%, representing almost a 50-50 split between CHD and persistent LV dysfunction from other causes.

Reference: "Refractory Left Ventricular Dysfunction in Neonates" - Youtube of NHRC by Dr. Gary Beasley. 2025. 

List of LV functional markers by Echocardiography

• M-Mode Echocardiography:

  • Fractional Shortening (FS)

  • Ejection Fraction (EF) by Teichholz

  • LV dimensions (LVIDd, LVIDs)

  • End systolic wall stress (see: Mean velocity of circumferential fiber shortening)

• Two-Dimensional Echocardiography (2D):

  • Global LV systolic function

  • Regional wall motion abnormalities - Often used in adult scoring systems.

    • Normal motion (score 1),  Hypokinesia (score 2), Akinesia (score 3), Dyskinesia (Score 4). The Wall Motion Score Index (WMSI) is calculated for the 17 segments of the left ventricle. The score is calculated by cumulating the number of points (a score for each segment) and dividing this by 17. When all segments move normally, the ratio is 1 (17 divided by 17). In adults, a WMSI >1.7 is indicative of heart failure.

    • Assessment of wall motion abnormalities during systole and diastole

  • LV volumes (end-diastolic and end-systolic)

  • LV mass

  • LV wall thickness

  • LV shape and geometry

• Doppler Echocardiography:

  • Pulsed-wave Doppler:

    • LV inflow velocities (E/A ratio, E wave deceleration time)

    • Tissue Doppler Imaging (TDI) velocities (S', E', A')

    • Index of Myocardial Performance (IMP / MPI / Tei Index): Combined measure of systolic and diastolic function - can also be calculated by TDI

  • Continuous-wave Doppler:

    • LV outflow tract velocities (velocity-time integral)

  • Color Doppler:

    • Assessment of regurgitant flow (mitral or aortic valve regurgitation)

• Tissue Doppler Imaging (TDI):

  • Systolic (S'), early diastolic (E'), and late diastolic (A') velocities of myocardial segments

  • TDI-derived indices (e.g., E/E' ratio for assessing LV filling pressure)

  • LV Dyssynchrony: Assessing temporal coordination of LV contraction (by TDI or strain imaging)

  • Index of Myocardial Performance (IMP / MPI / Tei Index): Combined measure of systolic and diastolic function

• Speckle Tracking Echocardiography (STE):

  • Global longitudinal strain (GLS)

  • Radial and circumferential strain

  • Segmental strain analysis

  • Strain rate imaging

  • Other deformational markers by STE

  • LV Twist and Torsion: Measures of LV rotational mechanics (more challenging than by 3D echocardiography due to temporal/loading changes during image acquisition)

  • LV Dyssynchrony: Assessing temporal coordination of LV contraction (by TDI or strain imaging)

• Myocardial Performance Indices (Tei Index):

  • Tei index (MPI) is a combined systolic and diastolic index of myocardial performance

• 3D Echocardiography:

  • 3D assessment of LV volumes, ejection fraction, and deformation (strain)

  • Better visualization of complex cardiac structures

  • LV Twist and Torsion: Measures of LV rotational mechanics

  • LV Dyssynchrony: Assessing temporal coordination of LV contraction (by TDI or strain imaging)

• LV Sphericity Index:

  • Evaluates LV shape and remodeling

• Endocardial Velocity Gradient (EVG):

  • Evaluates changes in LV contraction patterns

• Papillary Muscle Function:

  • Assessment of papillary muscle movement and mitral valve function

• Estimation of Stroke Work and Cardiac Output:

  • Calculations based on LV volumes and velocities - Article 1; Article 2.

Left ventricular Diastolic Function

See article here by ASE: Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography and for Heart Failure With Preserved Ejection Fraction Diagnosis: An Update From the American Society of Echocardiography Nagueh, Sherif F. et al. Journal of the American Society of Echocardiography, Volume 38, Issue 7, 537 - 569

LV dysfunction in a newborn with septic shock

Significant left ventricular dysfunction and significant tachycardia (heart rate 220 - in an attempt to maintain output in the context of significant systolic dysfunction) in a newborn with sepsis from a TnECHO performed by Dr Brahim Bensouda at Hôpital Maisonneuve-Rosemont from the TnECHO-Quebec Collaborative. Big thanks for sharing this example. Now in the LV Function section. 

The heart rate of 220 bpm (tachycardia) can be appreciated as a compensatory mechanism to maintain cardiac output in the context of significant left ventricular (LV) systolic dysfunction. The LV appears well-filled, and the left atrium (LA) is appropriately sized, suggesting adequate preload. This highlights the importance of thoroughly evaluating cardiac function in neonatal sepsis before selecting a specific treatment approach. While many neonates with sepsis will develop "warm shock" characterized by decreased systemic vascular resistance (SVR), others may exhibit an element of cardiac dysfunction. Additionally, a drop in SVR can sometimes "mask" underlying LV dysfunction, as the reduced afterload makes it less strenuous for the LV to eject blood, giving the appearance of normal function. If a vasopressor is introduced and the clinical condition does not improve, it is essential to reassess LV function. These patients may have LV systolic compromise exacerbated by the increase in SVR, necessitating adjustments to their management plan.

LV dysfunction in neonatal Permanent Junctional Reciprocating Tachycardia

Infant who had episodes of protracted arrhythmias secondary to PJRT with residual LV dysfunction in A5C, A2C and A4C.

LV dysfunction in a term newborn with HIE on therapeutic hypothermia

Premature newborn with asphyxia, RDS and hypoxic respiratory failure

Parasternal short axis demonstrating some degree of LV performance anomaly (moderate to severe). The flow through the aortic valve is almost completely filtered at a Nyquist of 68 cm/second, indicating that the systolic dysfunction impairs flow velocity generation in the outflow tract (possibly with secondary decreased output). 

Sweep in parasternal short axis indicates that the apex seems to be more affected than the papillary area and base. 

Degree of biventricular dysfunction with a depressed TAPSE. 

Unobstructed LV outflow tract. This patient also has some mild MR and TR, indicating some suffering of the underlying ventricle during the asphyxiated event (papillary muscle subendocardial ischemia)

Bidirectional PDA from isosystemic pulmonary pressure (PVR) and possibly decreased LV output from LV dysfunction. 

Altered TDI profile, with S' depressed for both ventricles. 

LV dysfunction in the context of Congenital Diaphragmatic Hernia

Abnormal strain (deformation) using speckle tracking echocardiography for the LV. 

Case of biventricular dysfunction in the context of HIE

Echocardiography on day 1 - "normal" BP (mean BP 45)

RV FAC is decreased at 19%

LV focuse view. Colour shows that there is some mild mitral insufficiency, possibly from subendocardial ischemia to the papillary muscles (proxy that this LV has suffered an event of perinatal asphyxia).  

LV lateral wall and septal wall with depressed systolic peak velocities by tissue doppler imaging. 

Depressed EF by Simpson's in A4C (33%)

No obvious coarctation with appropriate aortic caliber and laminar flow. A restrictive PDA may be observed (bidirectional in nature, although not fully appreciated from these clips). 

Echocardiography after Epinephrine IV

Echocardiography on day 2 - after addition of Milrinone IV

Improved LV and RV function on the A4C

Lung ultrasound - showcasing some degree of free fluid around the heart. 

Neonatal Heart Failure and Cardiomyopathy by Dr Alami

Presented at the McGill Neonatal Conference 2022

In above example, the PHT is 200 msec. The peak diastolic velocity gradient is 26 mmHg. If the diastolic BP in the Aorta is around 35, it informs you that the diastolic LV pressure is around 35-26 mmHg (9 mmHg) at the beginning of diastole, and 35-13=22 mmHg at end of diastole.

In aortic regurgitation (AR), pressure half-time (PHT) is an echocardiographic Doppler parameter that provides an indirect estimate of the severity of regurgitation.

• Pressure Half-Time (PHT): the time (in milliseconds) it takes for the pressure gradient between the aorta and the left ventricle to decrease by half during diastole.

• Measured using continuous wave Doppler of the AR jet in the apical 5-chamber or long-axis view.
  
  

>500 ms: Mild AR

200–500 ms: Moderate AR

<200 ms: Severe AR (suggests rapid pressure equalization)

• In severe AR, blood rapidly flows back into the LV → the aortic and LV pressures equalize quickly → shorter PHT.

• In milder AR, the flow is slower and pressure equalizes more gradually, resulting in a longer PHT.

• PHT is load-dependent and affected by:

  1. LV diastolic compliance

  2. Aortic pressure

  3. Heart rate
     
     

• Not reliable in:

  • Acute AR (pressures equalize rapidly due to noncompliant LV)

  • Aortic stenosis or high afterload states
    
    

• Should always be interpreted in context with other parameters (vena contracta, jet width, flow reversal in descending aorta, regurgitant volume/fraction, etc.)