Case Review Dynamic Assessment of the Fontan Part I: New Horizons in Medical...

In any circulation, blood flow per unit time is dependent upon the drop in pressure across the vascular bed and the vascular resistance (Ohm's law).

Biventricular circulation is characterized by low right ventricular pressure, low pulmonary arterial pressure, and low pulmonary vascular resistance.

During exercise in biventricular circulation, cardiac output can increase to approximately 5 times baseline cardiac output.

The pulmonary vascular resistance falls characteristically during exercise in biventricular circulation, allowing for substantial augmentation of pulmonary blood flow.

In the Fontan circuit, the pulmonary vascular resistance is typically both fixed and elevated.

In Fontan circulation, baseline cardiac output is typically near normal but a bit reduced, 70 to 80%.

Central venous pressure in Fontan patients is chronically elevated because there is no ventricle to do the work of the subpulmonary blood flow.

With exercise in Fontan patients, cardiac output increases quite a bit more limited than in the two ventricle population, characterized by increased central venous pressure and increased pulmonary vascular resistance.

At rest with zero exercise, cardiac output in typical or good Fontan patients is 70 to 80% of a normal biventricular patient, and identifying differences between these two populations may be subtle.

With augmentation of cardiac output or with stress or exercise, the difference between the Fontan patient and the biventricular patient becomes substantially increased.

The limitations of cardiac output in the Fontan circulation can be distilled down to pulmonary vascular resistance, diastolic function of the ventricle, and systolic function of the ventricle.

Systolic function is typically preserved in Fontan patients, at least preserved until very late in the clinical presentation with difficulties.

Most or all variables in Fontan circulation may be pretty typical or near normal at rest, thus to understand limitations, one must evaluate these variables in a dynamic or stressed state.

In a series of Fontan patients who underwent supine exercise with invasive hemodynamics, pulmonary vascular resistance was elevated at rest and with exercise, the pulmonary vascular resistance was quite static and did not decrease as expected with maximal exercise.

In patients with biventricular circulation, pulmonary vascular resistance begins lower and falls with exercise.

The Pediatric Heart Network Fuel trial is a randomized trial of 400 Fontan patients, with 200 receiving udenafil (a PDE5 inhibitor) and 200 receiving placebo, evaluating exercise capacity after 6 months of therapy.

In a study comparing Fontan patients with normal diastolic function versus those with diastolic dysfunction by echocardiography, patients with diastolic dysfunction had reduced peak VO2 and peak work with both supine and upright exercise.

Echocardiographic measures of diastolic function have not been validated in a Fontan population.

Invasive assessment of end-diastolic pressure in symptomatic Fontan patients is frequently unrevealing in the resting state because patients are often preload starved from being NPO, lying supine, and not undergoing stress.

In a protocol of rapid volume expansion (ventricular stress testing) in 46 Fontan patients, ventricular filling pressure (end-diastolic pressure) was significantly increased after exposure to volume, while transpulmonary gradient, pulmonary vascular resistance, and cardiac index were not significantly affected.

About 35% of Fontan patients demonstrated occult diastolic dysfunction, defined as a post volume challenge end-diastolic pressure of greater than or equal to 15 millimeters of mercury.

In univariate analysis, higher baseline end-diastolic pressure, longer duration of Fontan circulation, and lower baseline cardiac index were associated with higher fluid challenge end-diastolic pressure.

Longer duration of Fontan circulation was associated with a greater change in filling pressure during volume challenge.

In multivariable analysis, baseline end-diastolic pressure was the only finding associated with the final end-diastolic pressure after volume challenge.

The volume challenge protocol has been shared with a number of other large congenital heart centers and has now been performed in over 100 patients.

Fontan patients can have the presence of mechanical dyssynchrony without electrical dyssynchrony, which contributes to overall ventricular dysfunction, both systolic and diastolic.

Acute improvements in ventricular mechanics from pacing could translate to long-term clinical benefits, though this is an unproven assertion.

In the catheterization laboratory, a multimodality setup with conductance catheter feeds, electrical anatomic mapping, fluoro, ECG, and voltage mapping can identify ideal pacing sites and demonstrate ventricular mechanic changes at each site.

Dynamic assessment of the Fontan circulation might provide substantial insight beyond what can be obtained in the resting state.

Pathologies in pulmonary vascular resistance and diastolic function are likely to play critical roles in the limitations of Fontan patients.

In the Fuel trial with 400 patients, efforts have not been made to identify those patients who specifically have problems with pulmonary vascular resistance before inclusion in the trial.

Patients with relatively low pulmonary vascular resistance but substantial ventricular noncompliance may not respond to PDE5 inhibitor therapy if the drug does not have lusotropic effects to overcome ventricular fibrosis and noncompliance.

BNP was measured after exercise in the invasive exercise cohort, and almost universally it was a meaningless measure, with every patient's number between 15 and 40.

The easy biomarker has proved difficult to identify in Fontan patients because their end-diastolic pressure is probably quite low and not straining their atrium.

Hideki Senzaki's group has looked at profibrotic markers in the blood in the Fontan circulation, with some patients having very high levels of circulating effectors of fibrosis.