Congestive Heart Failure: Life Expectancy and Prognosis

Unique Cell-based Approach For Pulmonary Arterial Hypertension Shown To Be Safe

Infusions of potentially therapeutic cells derived from the heart are safe for people with pulmonary arterial hypertension, a form of high blood pressure that occurs in the blood vessels of the lungs and typically affects middle-aged women, according to a study led by Cedars-Sinai investigators.

The Phase I clinical trial results are published in the peer-reviewed journal eBioMedicine, a Lancet journal.

"Although several drugs are approved for pulmonary arterial hypertension, mortality remains high," said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai, the Mark S. Siegel Family Foundation Distinguished Professor and senior author of the study. "We tried a fundamentally different approach -- cell therapy delivered into the pulmonary artery -- and found encouraging results, in patients already on combination conventional therapy."

Pulmonary arterial hypertension is a rare disease, affecting fewer than 100 people per million. There currently is no cure and the average median life expectancy on treatment for most patients is roughly 6.2 years after diagnosis.

Currently approved medications for the condition aim to open up blood vessels in the lungs, allowing for better blood flow; however, studies on lungs in patients on treatment still show severe occlusive vessel changes. Further, these medications don't address many of the complex underlying mechanisms that cause the high pulmonary pressures. Even on medication, people with pulmonary arterial hypertension can develop severe dysfunction in the right ventricle of the heart, the part that pumps blood to the lungs and whose function correlates best with survival.

Cedars-Sinai investigators are experimenting with using cardiosphere-derived cells (CDCs) to address some of the biological processes involved in pulmonary arterial hypertension. CDCs were first developed and characterized by Marbán. They have been used in multiple clinical trials for a variety of diseases, most recently, Duchenne muscular dystrophy. These are cells derived from human heart tissue that Marbán and colleagues have discovered reduce inflammation in the body and exert beneficial effects on the immune system.

Called the ALPHA study, this clinical trial was conducted in two phases. In the first, six people with pulmonary arterial hypertension received an infusion of CDCs into their lungs. Three patients received an infusion of 50 million CDCs and the other three received an infusion of 100 million CDCs.

In the second phase, 10 people with pulmonary arterial hypertension were randomized to receive an infusion of 100 million CDCs and 10 people were randomized to receive infusions containing a placebo. Investigators performed right heart catheterization and cardiac MR imaging on each study participant before the infusions and four months after the infusions.

All the participants were on combination pulmonary arterial hypertension-specific medications throughout the course of the study.

The investigators tracked the health of participants for 12 months after the infusions. No adverse effects related to the infusions occurred during this time. Although this study was only designed to assess the safety of the CDC infusions, the investigators observed encouraging changes that might indicate the 16 people who had received the CDC infusions had improved cardiopulmonary health. People who received the infusions, for example, showed improved functioning in the heart's right ventricle and, at two months post-infusion, were able to walk a greater distance during a six-minute test than people who received placebo.

"The most important takeaway is that this approach is safe and feasible to do in people with pulmonary arterial hypertension," said Michael I. Lewis, MD, director of Respiratory Care Services at Cedars-Sinai, and first and corresponding author of the study. "These are encouraging exploratory findings that motivate moving on to more advanced studies."

The investigators plan additional trials to study the effects of repeated infusions of CDCs given to people with pulmonary arterial hypertension.

Cedars-Sinai investigators Mamoo Nakamura, MD; Dael Geft, MD; Yuri Matusov, MD; James Mirocha; Antoine Hage, MD; Victor Tapson, MD; Oleg A. Karpov, PhD; and Jennifer Van Eyk, PhD, also worked on the study.

Funding: The study was funded by the California Institute for Regenerative Medicine (CIRM), one of the world's largest institutions dedicated to three key areas of regenerative medicine -- research, education and patient access.

Treatment, Causes, And Symptoms Of Pulmonary Edema (Fluid In The Lungs)

Pulmonary edema is when fluid collects in the air sacs of the lungs, making it difficult to breathe. It can result from heart disease, pneumonia, and other health issues.

Pulmonary edema can be acute (occurring suddenly) or chronic (occurring more slowly over time). Acute pulmonary edema is a medical emergency and requires immediate medical attention.

Fluid in the lungs is often the result of congestive heart failure, in which the heart cannot keep up with the demands of the body.

Treatment of pulmonary edema usually focuses on improving respiratory function and addressing the source of the problem. It generally includes providing additional oxygen and medications to treat the underlying conditions.

This article explains the causes, symptoms, and treatment for pulmonary edema.

During typical breathing, the small air sacs in the lungs, known as alveoli, fill up with air. The lungs take in oxygen and expel carbon dioxide. Pulmonary edema occurs when fluid floods the alveoli.

This flooding causes two problems:

The bloodstream cannot get enough oxygen.

The body cannot expel carbon dioxide properly.

Common causes of pulmonary edema include:

pneumonia

sepsis or blood infection

exposure to certain chemicals

organ failure that causes fluid accumulation, such as:

near-drowning

inflammation

trauma

reaction to certain medications

overdose of certain drugs, including opioids

Pulmonary edema also occurs as part of a condition called acute respiratory distress syndrome (ARDS), a severe inflammation of the lungs that leads to significant breathing difficulties. Direct injury to the lungs or inflammation in other parts of the body can cause this condition.

Other possible causes include:

Cardiogenic pulmonary edema

Pulmonary edema that results from a direct problem with the heart is called cardiogenic pulmonary edema.

Congestive heart failure is a common cause of cardiogenic pulmonary edema. In this condition, the left ventricle is unable to pump out enough blood to meet the body's needs.

This causes a buildup of pressure in other parts of the circulatory system, forcing fluid into the air sacs of the lungs and other parts of the body.

The following heart-related problems can also lead to pulmonary edema:

Fluid overload: This can result from kidney failure or intravenous (IV) fluid therapy.

Hypertensive emergency: This is a severe increase in blood pressure that places excessive strain on the heart.

Pericardial effusion with tamponade: This is a buildup of fluid around the sac that covers the heart, which can decrease the heart's ability to pump.

Severe arrhythmia: This can be tachycardia (fast heartbeat) or bradycardia (slow heartbeat), both of which can result in poor heart function.

Severe heart attack: This can damage the muscle of the heart, making pumping difficult.

Abnormal heart valve: This can affect the flow of blood out of the heart.

Causes of pulmonary edema that are not due to poor heart function are called noncardiogenic and are often the result of ARDS.

Acute pulmonary edema causes significant breathing difficulties and can appear without warning. It is an emergency and requires immediate medical attention. Without proper treatment and support, it can be fatal.

In addition to breathing difficulties, the following symptoms can indicate acute pulmonary edema:

cough, often with a pink, frothy sputum

excessive sweating

anxiety and restlessness

feelings of suffocation

pale skin

wheezing

rapid or irregular heart rhythm (palpitations)

chest pain

If the pulmonary edema is chronic, symptoms are usually less severe until the body's system can no longer compensate. Symptoms may include:

difficulty breathing when lying flat (orthopnea)

swelling (edema) of feet or legs

rapid weight gain due to the accumulation of excess fluid

paroxysmal nocturnal dyspnea, or episodes of severe sudden breathlessness at night

fatigue

increased breathlessness with physical activity

A healthcare professional will typically begin with a physical exam. They will use a stethoscope to listen to the lungs for crackles and rapid breathing and to the heart for abnormal rhythms.

The healthcare professional will generally order blood tests to determine blood oxygen levels. They will often order additional blood tests to check the following:

electrolyte levels

kidney function

liver function

blood counts and blood markers of heart failure

An echocardiogram or an electrocardiogram (EKG) can help determine the condition of the heart.

The doctor may order a chest X-ray or a lung ultrasound to see whether there is any fluid in or around the lungs and to check the size of the heart. They may also order a CT scan.

Pulmonary edema happens when fluid collects inside the lungs, in the alveoli, making it difficult to breathe. Pleural effusion also involves fluid in the lung area and is sometimes called "water on the lungs."

However, in pleural effusion, fluid collects in the layers of the pleura that are outside the lungs.

Often, pleural effusion results from inflammation or a blockage due to a condition such as pneumonia, tuberculosis, or cancer. This is known as an exudative pleural effusion.

A transudative pleural effusion is another type that can also be due to excess fluid buildup in the body. This can result from heart failure, cirrhosis, or kidney failure.

Pulmonary edema can overlap with pneumonia, but it is a different condition. Pneumonia is an infection that often occurs as a complication of a respiratory infection such as the flu.

Though it can be difficult to distinguish between the two, a healthcare professional will try to make a correct diagnosis and determine the best course of treatment based on a person's detailed medical history, physical exam, and test results.

To raise a person's blood oxygen levels, a healthcare professional will administer oxygen through either a face mask or nasal cannulas, which are tiny plastic tubes that a healthcare professional places in a person's nose to provide oxygen.

Healthcare professionals may place a breathing tube in the trachea if a ventilator — a machine that helps a person breathe — is necessary.

If tests show that pulmonary edema is the result of a problem in the circulatory system, healthcare professionals will administer IV medications to help reduce fluid volume and regulate blood pressure.

Diuretics are the most commonly used medication and can help reduce fluid buildup by increasing the production of urine.

Depending on the specific cause and a person's symptoms, a healthcare professional may use any of the following other medications to treat pulmonary edema:

Vasodilators: These medications dilate the blood vessels to decrease pulmonary congestion.

Calcium channel blockers: These help reduce high blood pressure.

Inotropes: This type of medication can increase the force of heart muscle contractions so that the heart can pump blood throughout the body.

Morphine: This medication can help reduce anxiety and shortness of breath. However, because of its potential risks, healthcare professionals do not often recommend it.

People with an increased risk of developing pulmonary edema should follow a doctor's advice to manage the condition.

If a person has congestive heart failure, following a healthy, balanced diet and maintaining a moderate body weight can help ease symptoms and reduce the risk of future episodes of pulmonary edema.

Regular exercise also improves heart health, as do other lifestyle habits, including:

Reducing salt intake: Excess salt can lead to water retention, which requires the heart to work harder.

Lowering cholesterol levels: High cholesterol can lead to fatty deposits in the arteries, which can increase the risk of heart attack and stroke in addition to pulmonary edema.

Smoking cessation: Tobacco increases the risk of a number of health conditions, including heart disease, lung disease, and circulatory problems.

It is possible to minimize altitude-induced pulmonary edema by making a gradual ascent, taking medications before traveling, and avoiding excess exertion while progressing to higher altitudes.

Pulmonary edema can be a result of several conditions, including congestive heart failure, pneumonia, and sepsis.

In addition to causing symptoms such as cough, wheezing, chest pain, and excessive sweating, pulmonary edema can result in severe breathing difficulties and may be fatal without proper treatment.

For this reason, if a person experiences any symptoms of pulmonary edema, it's important to consult a doctor to determine the cause and the best course of treatment.

Read this article in Spanish.

The Early Detection Of Pulmonary Hypertension

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