Restrictive vs Constrictive Physiology

RHC Comprehensive Guide Restrictive vs Constrictive ATTR Cardiac Amyloidosis

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Executive Summary 1. Introduction 2. Normal RHC Values 3. Systematic Approach 4. Hemodynamic Differentiation 5. Illustrative Case 6. Comparative Hemodynamics 7. Comparative Reference 8. Nephrology Considerations 9. Summary References

Executive Summary

Key Points

RHC remains the gold standard for differentiating restrictive cardiomyopathy (RCM) from constrictive pericarditis (CP) — two conditions with similar clinical presentations but fundamentally different pathophysiology and treatment (1,2)
The commonly taught criterion of "pressure equalization" (RVEDP ≈ LVEDP) is a feature that favors constrictive pericarditis, not restrictive cardiomyopathy; in restriction, left-sided filling pressures typically exceed right-sided pressures because the infiltrated left ventricle is stiffer than the right (1,2,3)
The single most discriminating hemodynamic finding is respirophasic ventricular interdependence: discordant RV/LV systolic pressure changes with respiration favor constriction, while concordant changes favor restriction (2,3)
No single hemodynamic parameter reliably distinguishes CP from RCM in isolation; the diagnosis requires integration of multiple hemodynamic criteria with clinical context, imaging, and laboratory data (1,2)
An illustrative case is presented in which a 75-year-old male with suspected ATTR cardiac amyloidosis demonstrates hemodynamics consistent with restrictive physiology: RA 23, RVEDP 25, wedge 28, CI 1.15 L/min/m², with left-sided pressures exceeding right and severely elevated RVEDP/RVSP ratio
Consulting services that identify cardiac ascites should consider facilitating direct referral to cardiac amyloidosis programs when the clinical picture suggests infiltrative cardiomyopathy, rather than simply excluding hepatic disease (4,5)

1. Introduction: Why Right Heart Catheterization Matters

Right heart catheterization provides direct measurement of intracardiac pressures, cardiac output, and vascular resistances that cannot be reliably obtained by any noninvasive modality. While echocardiography, cardiac MRI, and CT provide invaluable structural and functional information, they estimate hemodynamics through indirect calculations and assumptions that may fail in precisely the patients who need hemodynamic data most — those with discordant clinical and imaging findings (1,2).

The clinical scenario that most commonly demands RHC for definitive hemodynamic assessment is the patient with heart failure and preserved ejection fraction whose clinical severity appears disproportionate to echocardiographic findings. This is precisely the scenario encountered in infiltrative cardiomyopathies such as ATTR amyloidosis, where the echocardiographic ejection fraction can appear reassuringly normal while the cardiac output is critically reduced (4,5).

2. Normal Right Heart Catheterization Values

Parameter	Normal Range	Unit
Right atrial pressure (mean)	0–8	mmHg
Right ventricular systolic pressure	15–30	mmHg
Right ventricular end-diastolic pressure (RVEDP)	0–8	mmHg
Pulmonary artery systolic pressure	15–30	mmHg
Pulmonary artery diastolic pressure	4–12	mmHg
Mean pulmonary artery pressure (mPAP)	10–20	mmHg
Pulmonary capillary wedge pressure (PCWP)	4–12	mmHg
Cardiac output	4.0–8.0	L/min
Cardiac index	2.5–4.0	L/min/m²
Pulmonary vascular resistance (PVR)	0.25–1.6	Wood units
Systemic vascular resistance (SVR)	10–20	Wood units
Mixed venous oxygen saturation (SvO₂)	65–75	%

2.1 Key Derived Parameters

Transpulmonary gradient (TPG): mPAP − PCWP. Normal < 12 mmHg. Elevated TPG in the setting of elevated PCWP suggests a precapillary component to pulmonary hypertension.

Diastolic pulmonary gradient (DPG): PA diastolic − PCWP. Normal < 7 mmHg. An elevated DPG (≥ 7 mmHg) in the setting of elevated PCWP defines combined pre- and post-capillary pulmonary hypertension (Cpc-PH).

RVEDP/RVSP ratio: Ratio > 1/3 (0.33) has traditionally been cited as favoring constriction, though significant overlap exists (2,3).

Fick cardiac output: CO = VO₂ / (CaO₂ − CvO₂) × 10. Preferred when thermodilution is unreliable (severe TR).

3. Systematic Approach to RHC Interpretation

Step 1: Identify the pressure profile — examine each chamber sequentially from RA to PCWP.

Step 2: Assess filling pressures — elevated RA/RVEDP indicates right heart congestion; elevated PCWP indicates left-sided diastolic dysfunction.

Step 3: Evaluate cardiac output and index — CI < 2.2 indicates compromise; CI < 1.8 is cardiogenic shock; CI < 1.5 is critical.

Step 4: Assess mixed venous oxygen saturation — SvO₂ < 65% indicates increased extraction compensating for reduced delivery.

Step 5: Characterize pulmonary hypertension if mPAP > 20 mmHg.

Pattern	PCWP	TPG	DPG	Interpretation
Isolated post-capillary PH (IpcPH)	> 15	< 12	< 7	Passive congestion from left heart disease
Combined pre/post-capillary PH (CpcPH)	> 15	≥ 12	≥ 7	Left heart disease PLUS pulmonary vascular remodeling
Precapillary PH	≤ 15	≥ 12	≥ 7	Primary pulmonary vascular disease (PAH, CTEPH)

Step 6: Differentiate restrictive vs. constrictive physiology — this is the most clinically challenging step and is addressed in detail below.

4. Restrictive Cardiomyopathy vs. Constrictive Pericarditis: Hemodynamic Differentiation

4.1 The Fundamental Pathophysiologic Distinction

In constrictive pericarditis, the pericardium is rigid and noncompliant. It encases both ventricles in a fixed-volume shell, creating exaggerated ventricular interdependence and dissociation between intrathoracic and intracardiac pressures. Both ventricles are equally constrained, so filling pressures tend to equalize (1,2,3).

In restrictive cardiomyopathy, the myocardium itself is stiff from infiltration (amyloid, iron), fibrosis, or endocardial disease. Each ventricle is independently stiff. There is no fixed pericardial shell, so ventricular interdependence is normal. Because the left ventricle is typically stiffer than the right (more myocardial mass to infiltrate), left-sided filling pressures tend to exceed right-sided pressures (1,2,3).

4.2 Traditional Hemodynamic Criteria

Hemodynamic Criterion	Favors Constriction	Favors Restriction
LVEDP − RVEDP	≤ 5 mmHg (equalized)	> 5 mmHg (LVEDP exceeds RVEDP)
RVEDP/RVSP ratio	> 1/3 (> 0.33)	< 1/3 (< 0.33)*
RV systolic pressure	≤ 50 mmHg (usually ≤ 40)	> 50 mmHg (may be higher)
Dip-and-plateau ("square root sign")	Present	Present (NOT discriminating)
Respirophasic ventricular interdependence	Discordant (RV↑, LV↓ with inspiration)	Concordant (RV and LV move together)
Kussmaul sign (RA rise with inspiration)	Often present	May be present (less specific)

*The RVEDP/RVSP ratio criterion has been called into question by multiple studies showing substantial overlap. See Section 4.3.

Warning: The "square root sign" (dip-and-plateau pattern in ventricular diastolic pressure) is NOT a discriminating feature between CP and RCM. It is present in both conditions and also occurs in congestive heart failure, bradycardia, and right ventricular infarction. Its presence confirms abnormal diastolic filling but does not identify the cause (2,3).

4.3 The Most Discriminating Criterion: Respirophasic Ventricular Interdependence

The single most sensitive and specific hemodynamic criterion for differentiating CP from RCM is the pattern of simultaneous RV and LV systolic pressure changes during respiration (2,3).

Technique: Simultaneous high-fidelity pressure recordings from catheters in both the RV and LV during normal unassisted respiration.

In constriction (discordant): During inspiration, increased venous return causes the interventricular septum to shift leftward, compressing the LV within the fixed pericardial volume. RV systolic pressure increases while LV systolic pressure decreases.

In restriction (concordant): Both ventricles respond similarly to changes in intrathoracic pressure through a normal, compliant pericardium. Both RV and LV systolic pressures move in the same direction.

In the landmark study by Talreja et al. (2008), this assessment had sensitivity and specificity exceeding 90% — substantially superior to all other individual hemodynamic criteria (3).

Clinical Pearl: If your institution's catheterization laboratory does not routinely perform simultaneous biventricular pressure measurements, you should specifically request this protocol when the clinical question is constriction vs. restriction.

4.4 A Common Misconception: "Pressure Equalization Means Restriction"

A widespread misunderstanding — even among experienced clinicians — is that equalization of right and left ventricular filling pressures supports the diagnosis of restrictive cardiomyopathy. This is incorrect. Pressure equalization is a classic feature of constrictive pericarditis. In restriction, the independently stiff ventricles typically have unequal filling pressures, with LVEDP exceeding RVEDP (1,2,3).

However, equalization can also occur in advanced restrictive cardiomyopathy when RV pressures become severely elevated. In end-stage amyloidosis with biventricular failure, the RVEDP may rise to approach the LVEDP. Therefore, equalization does not exclude restriction; it simply does not favor it over constriction (2,3).

Pressure Relationship	Primary Interpretation	Important Caveat
LVEDP >> RVEDP (difference > 5 mmHg)	Strongly favors restriction	Virtually excludes pure constriction
LVEDP ≈ RVEDP (difference ≤ 5 mmHg)	Favors constriction	Can also occur in advanced restriction with biventricular involvement
RVEDP > LVEDP	Unusual	Consider RV infarction, severe TR, or pulmonary disease

5. Applying These Principles: The Illustrative Case

5.1 The Hemodynamic Data

Patient A: a 75-year-old male with suspected ATTR amyloid cardiomyopathy presenting with diuretic-refractory ascites (bumetanide 4 mg BID, dapagliflozin, spironolactone), EF 55%, and CT findings of "cirrhosis."

Parameter	Measured Value	Normal Range	Interpretation
Right atrial pressure (RA)	23 mmHg	0–8 mmHg	Severely elevated (nearly 3× upper limit)
RV systolic pressure	43 mmHg	15–30 mmHg	Moderately elevated
RV end-diastolic pressure (RVEDP)	25 mmHg	0–8 mmHg	Severely elevated
PA systolic pressure	54 mmHg	15–30 mmHg	Moderately-severely elevated
PA diastolic pressure	34 mmHg	4–12 mmHg	Severely elevated
Pulmonary capillary wedge pressure (PCWP)	28 mmHg	4–12 mmHg	Severely elevated
Cardiac output	2.66 L/min	4.0–8.0 L/min	Critically reduced
Cardiac index	1.15 L/min/m²	2.5–4.0 L/min/m²	Cardiogenic shock range
RA oxygen saturation	64%	65–75%	Low (reduced delivery, increased extraction)
PA oxygen saturation (SvO₂)	65%	65–75%	Low-normal (borderline tissue hypoperfusion)

5.2 Step-by-Step Interpretation

Step 1: Overall pressure profile. Every measured pressure is severely elevated. The RA pressure of 23 mmHg immediately explains the massive ascites, congestive hepatopathy, and diuretic resistance.

Step 2: Filling pressure analysis. Both right-sided (RA 23, RVEDP 25) and left-sided (PCWP 28) filling pressures are severely elevated. The PCWP exceeds the RVEDP by 3 mmHg — within the "equalization" zone but in the direction expected for restriction.

Step 3: Cardiac output and mixed venous saturation. A cardiac index of 1.15 L/min/m² is in the cardiogenic shock range. The SvO₂ of 64–65% confirms increased systemic oxygen extraction.

Step 4: EF–cardiac output dissociation. EF 55% with CI 1.15 is the hemodynamic hallmark of restrictive cardiomyopathy. The ventricle fills with ~45–50 mL instead of 120 mL, ejects 55% of that tiny volume, producing a stroke volume of ~25 mL (normal ~70 mL).

This case illustrates the single most dangerous cognitive trap in cardiac amyloidosis diagnosis. The 2020 AHA Scientific Statement explicitly identifies the preserved EF as a primary driver of diagnostic failure (4). Ladefoged et al. (2020) documented a median diagnostic delay of 13 months (10). Survey data indicate that 44% of cardiac amyloidosis patients are initially misdiagnosed (11). Only 10% of physicians systematically screen HFpEF patients for cardiac amyloidosis (12).

Step 5: Pulmonary hypertension classification. mPAP ≈ 41 mmHg. TPG = 13 mmHg. DPG = 6 mmHg. Pattern consistent with combined pre- and post-capillary PH (Cpc-PH).

Step 6: RVEDP/RVSP ratio. 25/43 = 0.58. This exceeds the 1/3 threshold but reflects severity of diastolic dysfunction, not pericardial constraint.

Clinical Pearl: The RVEDP/RVSP ratio is the hemodynamic parameter most commonly misapplied in differentiating CP from RCM. In severe restrictive disease with biventricular involvement, the RVEDP can be so profoundly elevated that the ratio exceeds 1/3 despite clearly restrictive physiology. Always interpret the ratio in the context of the absolute pressure values and the overall hemodynamic profile (2,3).

Step 7: What is missing? Simultaneous biventricular pressure recording with respirophasic interdependence analysis was not documented. This is a limitation. However, the clinical context and converging hemodynamic findings make restrictive cardiomyopathy highly probable.

5.3 Summary: Does This Catheterization Support Restrictive Cardiomyopathy?

Criterion	This Patient	Interpretation
PCWP − RVEDP	28 − 25 = +3 mmHg	Left exceeds right (direction favors RCM); narrow gap reflects advanced biventricular disease
RVEDP/RVSP ratio	25/43 = 0.58 (> 1/3)	Elevated due to severe biventricular diastolic dysfunction, not pericardial constraint
RVSP	43 mmHg	Consistent with secondary PH, not fixed pericardial constraint
EF–CO dissociation	EF 55% / CI 1.15	Classic restrictive physiology
Clinical context	75M, no pericardial disease risk, increased wall thickness	Strongly favors infiltrative RCM (amyloid) over CP
Ventricular interdependence	Not assessed	Would be definitive if available

Conclusion: The hemodynamic profile is consistent with restrictive cardiomyopathy from suspected ATTR amyloidosis. The narrow PCWP-RVEDP gradient reflects the severity and biventricular nature of the disease rather than equalization from pericardial constraint. The preserved EF with critically reduced cardiac output is the hemodynamic fingerprint of infiltrative restrictive disease.

6. Hemodynamic Profiles: A Comparative Reference

Parameter	Restrictive CM (Amyloid)	Constrictive Pericarditis	Severe HFpEF	Cardiac Tamponade
RA pressure	Elevated (15–25+)	Elevated (15–25+)	Mildly elevated (10–18)	Elevated, equals PCWP
RVEDP	Elevated	Elevated	Mildly elevated	Elevated
PCWP	Elevated (> RVEDP usually)	Elevated (≈ RVEDP)	Elevated	Elevated (≈ RA)
LVEDP − RVEDP	> 5 mmHg (early); narrows in advanced disease	≤ 5 mmHg	Variable	≈ 0 (equalization)
Cardiac output	Reduced to severely reduced	Reduced	Mildly-moderately reduced	Reduced
Dip-and-plateau	Present	Present	Absent or subtle	Absent
Kussmaul sign	May be present	Usually present	Absent	Pulsus paradoxus instead
RVSP	May be > 50 mmHg	Usually ≤ 50 mmHg	Variable	Reduced
Ventricular interdependence	Concordant	Discordant	Not significant	Enhanced
Pericardial effusion	Small or absent	Absent (thickened)	Small or absent	Large (by definition)
EF	Preserved (50–65%)	Preserved	Preserved (≥ 50%)	Reduced in severe
Key feature	EF–CO dissociation; thick walls	Pericardial thickening; septal bounce; e′ preserved	HTN, DM, age	Large effusion; electrical alternans

8. Special Considerations for Nephrology

8.1 Hemodynamics and Renal Perfusion

The transrenal perfusion gradient — the difference between mean arterial pressure and renal venous pressure (approximated by RA/CVP) — determines effective renal blood flow and GFR. In this patient, with an RA of 23 mmHg and reduced MAP from low cardiac output, the transrenal perfusion gradient is severely compromised from both sides: reduced inflow (forward failure) and elevated backpressure (congestive nephropathy). This dual mechanism explains the profound diuretic resistance (6).

8.2 The RA Pressure as a Predictor of Diuretic Resistance

RA pressure of 23 mmHg provides a quantitative explanation for why bumetanide 4 mg PO BID, dapagliflozin, and spironolactone are insufficient. At this level of venous congestion: oral absorption is impaired by gut edema, renal venous congestion reduces filtration fraction, and neurohormonal activation overwhelms the diuretic effect. RHC data provide the physiologic rationale for transitioning to IV diuretics, adding sequential nephron blockade with metolazone, and accepting the need for serial paracentesis (6).

8.3 Monitoring Hemodynamic Response to Treatment

If disease-modifying therapy (tafamidis, acoramidis) stabilizes the amyloid-infiltrated ventricle, repeat RHC can document hemodynamic improvement: declining filling pressures, improving cardiac output, and reduced pulmonary pressures — providing the nephrologist with objective hemodynamic benchmarks for tracking the cardiorenal response.

9. Summary and Key Teaching Points