Pulmonary Hypertension: Normal pulmonary-artery pressure is about 14 mm Hg at rest.

If the
pressure in the pulmonary artery is greater than 25 mm Hg at rest and 30 mm Hg during exercise, it is
abnormally high and is called pulmonary hypertension.
Classifications:
1. Pulmonary arterial hypertension (PAH)
1.1. Idiopathic PAH: PAH that has no known cause.
1.2. Heritable: passed from parents to children through genes
1.2.1. BMPR2 (Bone morphogenetic protein receptor type II)
1.2.2. ALK1, endoglin, SMAD9, CAV1, KCNK3
1.2.3. Unknown
1.3. Drug- and toxin-induced: caused by drugs or toxins, such as street drugs and certain diet
medicines
Drugs/Toxins: Unknown mechanism but thought to be due to altered growth factor
biology (eg, serotonin, platelet derived growth factor).
o Definite risk factors for PAH: appetite suppressants, toxic rapeseed oil, and
benfluorex.
While the reason for this is largely unknown, altered serotonin biology
may play a role.
Serotonin has been shown to induce growth of pulmonary artery
smooth muscle cells from patients with PAH
o Possible risk factors for PAH: amphetamines, L-tryptophan,
methamphetamines, cocaine, phenylpropanolamine, St. John's Wort,
dasatinib (tyrosine kinase inhibitor for CML), and interferon.
o In one study, cocaine or amphetamine use tripled the risk of developing PAH.
1.4. Associated with
1.4.1. Congenital heart diseases
o Congenital heart disease Left-to-right shunting increases flow through
the pulmonary vasculature, which causes shear forces that disrupt the
vascular endothelium and activate cellular mechanisms critical to the
pathogenesis and progression of PAH
o ASD: shunting is delayed until maturation of the pulmonary vasculature
occurs. The normal pulmonary vasculature is able to accommodate the
increased volume of flow by vasodilating and recruiting previously unperfused
vessels; thus, pulmonary artery pressures do not rise significantly in
most patients with an ASD until adult life
o VSD/PDA: The combined effect of volume overload and shear forces elevates
the pulmonary vascular resistance, which becomes fixed during childhood.
o Eisenmenger syndrome is the triad of
1- systemic-to-pulmonary cardiovascular communication (VSD or PDA)
2- pulmonary arterial disease

 3- cyanosis.
o Pulmonary arterial disease develops as a consequence of increased
pulmonary blood flow.
o Plasma levels of endothelin, a vasoconstrictor and stimulant of vascular
smooth muscle cell proliferation, are elevated in patients with PAH due to
congenital heart defects
o Plasma thromboxane B2 levels are also elevated in patients with PAH due to
congenital heart disease. Thromboxane B2 causes platelet activation and
constriction of pulmonary arterioles.
1.4.2. HIV infection
1.4.3. Portal hypertension
1.4.4. Connective tissue diseases
1.4.5. Schistosomiasis: infection caused by a parasite.
1. Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis
(PCH) : PAH that's caused by conditions that affect the veins and small blood vessels of the lungs.
1. Persistent pulmonary hypertension of the newborn (PPHN).
2. Pulmonary hypertension owing to left heart disease: Conditions that affect the left side of the heart,
such as mitral valve disease or long-term high blood pressure. Left heart disease is likely the most
common cause of PH.
2.1. Left ventricular systolic dysfunction
2.2. Left ventricular diastolic dysfunction
2.3. Valvular disease
2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital
cardiomyopathies
3. Pulmonary hypertension owing to chronic lung diseases and/or hypoxia
3.1. Chronic obstructive pulmonary disease
3.2. Interstitial lung disease: causes scarring of the lung tissue
3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern
3.4. Sleep-disordered breathing
3.5. Alveolar hypoventilation disorders
3.6. Chronic exposure to high altitude
3.7. Developmental abnormalities
4. Chronic thromboembolic pulmonary hypertension (CTEPH): caused by blood clots in the lungs or
blood clotting disorders.
5. Pulmonary hypertension with unclear multifactorial mechanisms
5.1. Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders,
splenectomy

5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis:

lymphangioleiomyomatosis, neurofibromatosis, vasculitis
5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental
pulmonary hypertension
Group 1 PAH
Pathophysiology Pulmonary arterial hypertension (PAH) is a proliferative vasculopathy,
characterized by vasoconstriction, cell proliferation, fibrosis, and thrombosis. Pathologic findings
include intimal hyperplasia and fibrosis, medial hypertrophy, and in situ thrombi of the small
pulmonary arteries and arterioles (plexiform lesions). The pathologic appearance of the small
pulmonary arteries and arterioles is qualitatively similar in all patients with group 1 PAH.
Genetic mutations: Mutations in the above listed genes have been variably associated with familial,
idiopathic, or hereditary hemorrhagic telangiectasia (HHT)-associated pulmonary hypertension
Group 2 through 5 PH The pathophysiology of WHO group 2, 3, 4, or 5 PH is less understood
than group 1 PAH. However, it is clear that overlap exists since vascular remodeling and increased
pulmonary vascular resistance are present in all groups.
Signs and symptoms of pulmonary hypertension (PH) may include:
Shortness of breath during routine activity, such as climbing two flights of stairs
Tiredness
Chest pain
A racing heartbeat
Pain on the upper right side of the abdomen
As PH worsens, you may find it hard to do any physical activities. At this point, other signs and
symptoms may include:
Feeling light-headed, especially during physical activity
Fainting at times
Swelling in your legs and ankles
cyanosis: A bluish color on your lips and skin
DIAGNOSIS
Medical and Family Histories:
signs and symptoms and how and when they began.
If pt has any other medical conditions that can cause PH.
any family members who have or have had PH. People who have a family history of PH are at
higher risk for the condition.
Physical Exam:

Heart and lungs exam with stethoscope.

Check your ankles and legs for swelling and your lips and skin for a bluish color.

Tests and Procedures To Confirm a Diagnosis

Echocardiography: This test can estimate the pressure in your pulmonary arteries. Echo also
can show the size and thickness of your right ventricle and how well it's working.
Chest x ray: shows whether your pulmonary arteries and right ventricle are enlarged.
o The pulmonary arteries and right ventricle may get larger if the right ventricle has to
work hard to pump blood through the pulmonary arteries.
o A chest x ray also may show signs of an underlying lung disease that's causing or
contributing to PH.
EKG (electrocardiogram): simple, painless test that records the heart's electrical activity.
o This test also shows whether your heart's rhythm is steady or irregular.
o An EKG may show whether your right ventricle is enlarged or strained.
Right heart catheterization: During this procedure, a thin, flexible tube called a catheter is put
into a blood vessel in your groin (upper thigh) or neck. The tube is threaded into the right side
of your heart and into the pulmonary arteries. Through the tube, your doctor can do tests and
treatments on your heart.
o measures the pressure in your pulmonary arteries.
o It also shows how well your heart is pumping blood to the rest of your body.
o Can find any leaks between the left and right side of the heart

Tests To Look for the Underlying Cause of Pulmonary Hypertension

Chest CT scan: creates pictures of the structures inside your chest, such as your heart, lungs,
and blood vessels. These pictures can show signs of PH or a condition that may be causing
PH.
Chest MRI. Chest magnetic resonance imaging, or chest MRI, shows how your right ventricle
is working. The test also shows blood flow in your lungs. Chest MRI also can help detect signs
of PH or an underlying condition causing PH.
Lung function tests. Lung function tests measure how much air you can breathe in and out,
how fast you can breathe air out, and how well your lungs deliver oxygen to your blood. These
tests can help detect a lung disease that may be causing PH.
Polysomnogram (PSG). This test records brain activity, eye movements, heart rate, and blood
pressure while you sleep. A PSG also measures the level of oxygen in your blood. A low
oxygen level during sleep is common in PH, and it can make the condition worse.
o A PSG usually is done while you stay overnight at a sleep center. For more information
about this test, go to the Diseases and Conditions Index Sleep Studies article.
Lung ventilation/perfusion (VQ) scan. A lung VQ scan measures air and blood flow in your
lungs. This test can help detect blood clots in your lung's blood vessels.
Blood tests. Blood tests are used to rule out other diseases, such as HIV, liver disease, and
autoimmune diseases (such as rheumatoid arthritis).

Finding Out the Severity of Pulmonary Hypertension

Exercise testing is used to find out the severity of PH. This testing consists of either a 6-minute walk
test or a cardiopulmonary exercise test.
A 6-minute walk test measures the distance you can quickly walk in 6 minutes. A cardiopulmonary
exercise test measures how well your lungs and heart work while you exercise on a treadmill or
bicycle.
During exercise testing, your doctor will rate your activity level. Your level is linked to the severity of
your PH. The rating system ranges from class 1 to class 4.
Functional classification of PH
Class 1 has no limits. You can do regular physical activities, such as walking or climbing stairs.
These activities don't cause PH symptoms, such as tiredness, shortness of breath, or chest
pain.
Class 2 has slight or mild limits. You're comfortable while resting, but regular physical activity
causes PH symptoms.
Class 3 has marked or noticeable limits. You're comfortable while resting. However, walking
even one or two blocks or climbing one flight of stairs can cause PH symptoms.
Class 4 has severe limits. You're not able to do any physical activity without discomfort. You
also may have PH symptoms while at rest.
Over time, you may need more exercise tests to find out how well your treatments are working. Each
time testing is done, your doctor will compare your activity level with the previous one.

LVAD Risk analysis

-This paper retrospectively reviewed the effect of BSI on survival of patients with long-term LVAD
support and assessed various risk factors related to their survival.
-109 patients with end-stage heart failure who underwent LVAD implantation as a bridge to heart
transplantation between May 1999 and December 2010.
-LVAD-associated BSI was defined as
(1) the same organism is isolated from drainage around the exit site or obtained through a
percutaneous aspiration of a fluid collection around the device,
(2) no other source for the BSI is identified, or
(3) the bacteremia is sustained despite appropriate antibiotic therapy or despite adequate drainage of
an identified source
-221 BSI events in 65/109 patients (60%) during LVAD support
-Four significant predictors of BSI after LVAD implantation:
1-heart failure duration longer than 405 days
2-postoperative acute renal failure requiring continuous hemofiltration
3-postoperative right ventricular failure
4-postoperative prolonged mechanical ventilation exceeding 2 weeks
-Out of 65 BSI pts, 32 pts died:
17 CVA
12 sepsis
3 R-ventricular failure
-Significant predictors of death in LVAD patients with BSI
non-idiopathic dilated cardiomyopathy,
preoperative levels of brain natriuretic peptides (BNP) of 1,850 pg/mL or higher,
preoperative total protein levels of 5.8 g/dL or lower,
postoperative total bilirubin levels of 1.8 mg/dL or higher,
postoperative acute renal failure requiring continuous hemofiltration,
postoperative right ventricular failure,
BSI caused by a pathogen other than gram-positive cocci

-The major finding in our study:

Worse survival in pts with BSI vs no BSI.
Significant pre-operative risk factor for BSI: heart failure duration longer than 405 days
Significant pre-operative risk factor for death:
preoperative BNP of 1,850 pg/mL or higher
preoperative total protein of 5.8 g/dL or lower

-Patients with a BSI caused by gram-positive cocci alone had better survival than those with a BSI
caused by another pathogen.

In conclusion, BSI had a significant effect on survival after LVAD implantation. Our results suggest
that urgent heart transplantation should be considered for LVAD patients with a BSI based on the
causative organism and right ventricular function.

LVAD and CVA

Retrospective study
Objective: if persistent BSI (as opposed to transient BSI) is associated with an increased risk of allcause CVA (hemorrhagic and/or ischemic) and all-cause mortality in patients who underwent HMII
implantation at our institution.

We classified BSI as persistent (pBSI) if the same organism grew in the blood on cultures 72 hours
apart despite antibiotics.
All other BSI was classified as non-persistent (non-pBSI)
153 LVADs implanted from 2008 to 2012 > 4 died on the day of LVAD implantation > 149 patients
included for final analysis
45 (30%) pts developed bacteremia:
28 (19%) pBSI
17 (11%) Non-pBSI
Pseudomonas aeruginosa (n-12) and Staphylococcus aureus (n-11) were the most common
organisms identified in our patients.
The most common source of infection was the LVAD driveline,
19 patients (13%) had CVA:
10/28 pts in pBSI group: 6 hemorrhagic and 4 ischemic
8/104 pts in control group: all ischemic
1/17 pt in non-pBSI group
Pseudomonas aeruginosa were associated with all-cause CVA.
INR and mean BP were not associated with CVA.
17 deaths in pBSI:
8: CVA
4: sepsis with multisystem organ failure
3: cardiac arrest
2: respiratory failure
7 pts with HCVA > all had pseudomonas infection > all died

In this retrospective single-center study, we found that pBSI in patients with HMII LVADs was
associated with increased mortality and all-cause CVA compared with patients with non-pBSI or no
BSI.
Pseudomonas aeruginosa was a particularly high-risk organism in our study, with a strong association
with HCVAs.
Occurrence of a HCVA in our population was associated with 100% mortality.
Patients supported with LVAD who develop HCVA associated with BSI have a very poor prognosis
and are unlikely to benefit from neurosurgical interventions.