Cardiac Hypertrophy

Managing a newborn with Hypertrophic Obstructive Cardiomyopathy (HOCM) and hemodynamic instability is a high-stakes balancing act. Unlike typical neonatal shock, the goal here is not to increase contractility, but rather to reduce obstruction and optimize diastolic filling, leading to improved systemic output. In HOCM, one of the issues is Systolic Anterior Motion (SAM) of the mitral valve, where the valve is sucked into the narrowed Left Ventricular Outflow Tract (LVOT) during systole, causing a dynamic obstruction. Another concern is the decreased left ventricular compliance, leading to raised LV end-diastolic pressure and possibly post-capillary pulmonary hypertension (this can present with significant pulmonary edema, and left to right restrictive inter-atrial shunting - depending on presence/size of the defect). These patients may present with pulmonary venous congestion. 

Strategies

• Preload Management

• Goal: Keep the ventricle "full" to stent the LVOT open.

• Purpose: Increasing the end-diastolic volume physically pushes the septum and mitral valve apart, reducing the degree of obstruction.

• Advantage: Most "physiologic" way to reduce the gradient without using drugs.

• Watch for: Over-distension leading to pulmonary edema, though these patients usually require higher-than-normal filling pressures (CVP 8–12 mmHg). 

• Judicious use of fluid bolus and maintenance fluid. While it is reasonable to avoid dehydration, excessive fluid administration can be detrimental as well. Some of these infants are infants of diabetic mother and are already on a supra-physiological total fluid intake due to the high glucose intake required to maintain normoglycemia. 

• Vasopressors (Increasing Systemic Afterload)

  • Agents: Phenylephrine, Vasopressin (sometimes norepinephrine = although it may have the undesirable side effect of increasing chronotropy and, as such, less favoured)

• Purpose: To increase Systemic Vascular Resistance (SVR). A higher afterload "back-pressures" the LVOT, helping to keep it open. It also delays LVOT opening which allows to increase modestly the filling time.

• Advantage: Phenylephrine is a pure alpha-agonist; it slows the heart rate (reflexively) and increases afterload without increasing contractility. Vasopressin is excellent for hypotension without affecting the heart rate or inotropy. Vasopressin may increase the risk of hyponatremia (theoretically), that can be present especially in infants of diabetic mother exposed to high total fluid intake due to glucose issues. 

• Watch for: Excessive vasoconstriction leading to decreased organ perfusion or gut ischemia.

• Beta-Blockers

  • Agents: Esmolol (acute/titratable), Propranolol (maintenance).

  • Purpose: To decrease heart rate (increasing diastolic filling time). However, they may have some inherent negative inotropy properties. While this can reduce the "venturi effect" that causes SAM, it can also lead to altered ventricular function (especially if there is concomittant RV dysfunction in the context of high PVR status). 

  • Advantage: Esmolol is short-acting and can be turned off quickly if the baby decompensates.

  • Watch for: Bradycardia and hypotension. Beta-blockers are contraindicated if there is overt low-output heart failure without significant LVOT obstruction. It is also agents that can induce bronchospasm. 

• Ventilation and Sedation

  • Purpose: To reduce the work of breathing and metabolic demand.

  • Strategy: Maintain high-normal CO2 to avoid tachycardia. Positive Pressure Ventilation (PPV) should be used carefully, as high mean airway pressures can decrease preload (venous return), which worsens HOCM.

  • Sedation and anelgesia (especially with agents like dexmedetomidine) should be considered to reduce metabolic demand and heart rate, avoid increase adrenergic stimulation such as with crying. Release of catecholamines will increase contractility, worsening the obstruction, and increase heart rate (decreases filling time)

• What to Avoid: Inotropes

  • Agents: Epinephrine, Dobutamine, Dopamine (and even Norepinephrine if you have access to other vasopressors without chronotropic effect). 

• The Rationale: These should generally be avoided or used with extreme caution because of their increasing heart rate capacity.

• The Danger: Increasing contractility (positive inotropy) or heart rate (positive chronotropy) worsens the LVOT obstruction and SAM, creating a "spiral" where the harder the heart pumps, the less blood actually leaves the ventricle.

• Norepinephrine: While it has alpha effects, its beta-1 activity can worsen the gradient. Only use if SVR is dangerously low and phenylephrine/vasopressin is insufficient.

• Milrinone: 

  • In the context of severe HOCM with hemodynamic instability, milrinone is generally avoided and should be approached with caution. Milrinone is an "inodilator"—it increases contractility (inotropy) and decreases systemic vascular resistance (vasodilation). In a HOCM patient, both of these actions  are less desirable. Strengthening the ventricular squeeze increases the velocity of blood through the narrow LVOT. This creates a stronger Venturi effect, which pulls the mitral valve into the septum (SAM), worsening the obstruction. Dropping the systemic blood pressure by reduction of SVR and LV afterload can reduce the "back-pressure" that helps keep the LVOT open (and make the LVOT open earler limiting filling time). A lower afterload allows the ventricle to empty more forcefully and completely, which makes the obstruction more severe. 

  • Milrinone is also a lusitropic agent that improves relaxation - which is the only potential benefit in this physiology. However, this benefit is almost always outweighed by the risks of increased SAM and hypotension. Despite the risks, Milrinone is sometimes considered in very specific, complex neonatal cases (such as an infant of a diabetic mother with HOCM and concurrent PPHN). If used, it is almost always paired with a Beta-blocker (like Esmolol) to counteract the increased contractility and heart rate, as well as with a vasopressor (vasopressin or phenylephrine) while still getting the benefits of relaxation (diastolic lusitropy).

• PGE

  • In the context of severe HOCM, Prostaglandin E1 (PGE1) is not typically a first-line therapy because HOCM is an intramyocardial structural disease, not a classic "ductal-dependent" lesion. However, in a newborn with hemodynamic collapse, its role is nuanced and depends entirely on the secondary consequences of the hypertrophied muscle. If the hypertrophy is so massive that it causes Critical Left Ventricular Outflow Tract (LVOT) Obstruction, the baby may present exactly like a "Left-Sided Obstructive Lesion" (e.g., Critical Aortic Stenosis). PGE1 can be used to maintain systemic perfusion via the Ductus Arteriosus (Right-to-Left shunting). If the LV cannot pump blood past the obstruction to the body, a patent ductus allows the Right Ventricle (RV) to take over systemic circulation. 

  • The "RV Pop-off": In cases where HOCM is associated with severe Pulmonary Hypertension (PPHN), keeping the ductus open acts as a "pressure-relief valve" for the RV, preventing right-sided heart failure. 

  • If the LVOT is significantly obstructed by the septum and SAM, the baby will die of cardiogenic shock without a ductus to provide systemic blood flow. 

  • As such, it can buy time to start Esmolol, vasopressor therapy and/or volume resuscitation. 

  • The Risks: Vasodilation - PGE1 is a potent systemic vasodilator. As discussed with Milrinone, dropping SVR is not desirable in HOCM. If the ductus is open but the SVR drops too low, it can worsen the LVOT obstruction and "steal" blood away from the coronary arteries. Like all neonates on PGE1, there is a high risk of apnea requiring intubation. You can also get hypotension from the drug's direct effect, which then triggers tachycardia—and tachycardia is the enemy of HOCM filling

• Pulmonary Vasodilators (iNO)

• Use with extreme caution, or not at all.

• Purpose: To treat concomittant pulmonary hypertension.

• The Risk: Inhaled Nitric Oxide (iNO) reduces Right Ventricular (RV) afterload. This can increase venous return to the left atrium, which is good, but it can also decrease the "splinting" effect the RV has on the septum, potentially worsening LVOT obstruction. It will promote left to right shunting at the ductal level, while many of these patients need some degree of right to left shunting if there is insufficient systemic flow due to the dynamic LVOT obstruction and reduction in LVO.

• Verdict: Generally avoided unless there is documented, severe PPHN that is the primary driver of instability. If the PFO is left to right, it informs that the LA pressure is higher than the RA pressure, and as such iNO should be avoided. 

• ECMO (The Last Resort)

  • Purpose: To provide total circulatory support when medical management fails to relieve the LVOT gradient or maintain perfusion.

  • VA-ECMO Unloads the heart and ensures end-organ perfusion.