Presentation by Dr. Jonathan R. Lindner MD at the 13th Annual Cheri Woo Scleroderma Education Seminar on March 8, 2014 in Portland, Oregon. The seminar is a free public service hosted by the Oregon Chapter of the Scleroderma Foundation.

1. Cardiovascular Manifestations
Systemic Sclerosis
Jonathan R Lindner, MD
M Lowell Edwards Professor of Cardiology
Knight Cardiovascular Institute
Oregon Health and Sciences University

2. Pathophysiology of SSc
Inflammation Thrombosis
Vasoconstriction Vessel wall
hyperplasia
Tissue injury
and fibrosis
Hypoxia

3. Cardiovascular Manifestations of SSc
Valve
disease?
Pericardial
disease
Cor Pulmonale Myocarditis/
Cardiomyopathy
Hypertrophy
Conduction
abnormalities
Microvascular
disease

4. Cardiac Complications:
Scope of the Problem
• Cardiac symptoms often go unnoticed
• Symptoms attributed to lung or musculoskeletal
disease
• Recognized primary cardiac involvement in 20-
25% of those with diffuse SSc (much higher on
autopsy series)
• Presence of cardiac involvement is a poor
prognostic feature and usually occurs in those
with more advanced disease

5. Pulmonary Hypertension in SSc
• High blood pressure in the lung arterial
circulation.
• Severe pulmonary hypertension affects 10-
12% of patients with SSc
• Mortality 50% within 3 yrs
• Most of the mortality is directly related to
effects on the right ventricle
• In those with long term survival there is
considerable morbidity from the effects on the
right ventricle

6. Koch ET, et al. Br J Rheumatol 1996;35:989
PAH and Survival in SSc

7. Right Heart Failure in SSc PAH
• For any given increase in pulmonary pressure,
the deleterious effect on the right heart is
greater in SSc than in other diseases of PAH

8. Right Heart Failure in SSc PAH
Right Heart FailureNormal

9. Secondary Tricuspid Regurgitation

10. Right Heart Failure:
Symptoms and Complications
• Fatigue, shortness of breath, exercise
intolerance
• Severe edema (swelling of legs, abdomen)
• Liver dysfunction and cirrhosis
• Gastrointestinal symptoms of bowel edema
• Heart rhythm disorders (atrial fibrillation,
ventricular tachycardia)

11. Risk Factors for PAH and
Right Heart Failure
• Late age of onset of SSc
• Pre-existing lung disease, smoking
• Raynaud’s
• Certain antibodies (anti-U3RNP)
• More severe SSc

12. How to Diagnose PAH

13. Treatment Options
Pulmonary vasodilators:
• Prostacyclin agonists
• Phosphodiesterase-E5 inhibitors
• Endothelin antagonists
• Calcium channel blockers
Immunosuppressive therapy
Diuretics
Oxygen
Digoxin
Lung transplantation
Experimental: Ivadrabine, Tyrosine kinase inhibitors

14. Left Ventricular Dysfunction in SSc
 Causes:
- Heart inflammation/fibrosis
- Small vessel dysfunction
- “Raynaud’s” of the heart vessels
 Occurs in approximately 5% of patients with
SSc
 Higher incidence with advanced age,
hypertension, kidney disease, pulmonary
disease, digital ulcers

15. Left Ventricular Dysfunction
Normal Dysfunction

16. Myocyte Damage from Microvascular Disease

17. Myositis and Vasculitis
Histology DE-Gd-MRI

18. Symptoms of LV Dysfunction
• Shortness of breath
• Fatigue, weakness
• Cough, frothy sputum
• Inability to sleep flat
Symptoms of Coronary Vasospasm
• Chest pain, acute shortneess of
breath
Symptoms of Myositis
• Chest pain, fever, fatigue

19. Occult LV Dysfunction:
Common First Manifestations
• Stroke
• Heart rhythm disturbance (atrial
fibrillation, ventricular fibrillation)
• Complications of poor blood flow (kidney
dysfunction, confusion)

20. Diagnosis
• Clinical suspicion
• Echocardiogram
• Once LV dysfunction is found, there is a
workup for causes not related to SSc
• Evaluation for myocarditis and
microvascular dysfunction

21. RNI Detection of Perfusion Defects
Stress Rest

22. MCE Evaluation of the Microcirculation

23. Treatment
• Diuretics
• ACE-inhibitors; Angiotensin receptor
blocking agents
• Beta blockers???
• If vasospasm suspected: calcium
channel blocking vasodilators or long-
acting nitroglycerine
• ICD
• Cardiac rehabilitation
• If myositis: immunosupppressive therapy

24. Diastolic Heart Failure
• No problem with the heart squeeze
• Problem exists with the relaxation of the
heart between squeezes
• Due to fibrosis and enlarged heart cells
that occurs with inflammation, early
microvascular disease, renal disease,
and hypertension

25. Diastolic Heart Failure

26. Pericarditis
Sharp chest pain
Positional pain
Respiratory variation
Fevers
Shortness of breath
Palpitations
Symptoms

27. Pericarditis in SSc
 Symptomatic pericarditis in 5-12%
 Detected by imaging/autopsy in 33-70%
 Common in limited scleroderma (CREST)
 More common if there is PAH
 Treatment with NSAIDs and/or steroids
 Complications of disease:
• Effusions (tamponade)
• Constriction

28. Pericardial Effusion

29. Pericardial Effusion
 Symptoms: chest pain, shortness of breath,
dizziness, fatigue, swelling
 When severe  cardiac collapse (tamponade)
 Hemodynamically significant effusion in 10%
of those with pericarditis
 Can also be associated with renal disease

30. Pericardial Effusion: Detection
1. Clinical suspicion
2. Physical exam
3. Imaging

31. Pericardial Constriction
• Encasement of the heart
• Symptoms: fatigue, chest pain, swelling
• Abdominal distention
• Atrial fibrillation

32. Pericardial Constriction

33. Treatment for Complications
• Drain fluid if it is causing more than mild
symptoms or endangering heart function
• For constriction, diuretics to unload the
heart
• Consider immunosuppressive therapy for
constriction or refractory/recurrent
effusion

34. What Does This Mean for You?
1. Awareness that there are cardiac manifestations in
SSc is the first and most important step to
discovering cardiovascular disease
2. Echocardiography is a common diagnostic test – it
is generally part of the routine screening for
pulmonary hypertension
3. More severe disease should lead to more frequent
screening
4. Do not discount symptoms of shortness of breath,
extreme fatigue, dizziness, chest pain
5. Aggressive treatment of hypertension
6. Other risk factor modification (exercise, smoking
cessation, diet)