That Dastardly Disease
Pulmonary Hypertension
A poem by Merle Reeseman ©
I used to be healthy; I used to be strong,
I used to work most all the day long.
And then it hit me without even a clue
I wasn’t quite sure just what I could do.
I saw many doctors and then all those tests
I was diagnosed with IPAH and you know the rest.
Pulmonary Hypertension the dastardly disease
It’s rare with no cure and progression will be
It affects the right side of heart – the lungs big time too
Those arteries get constricted and give out on you.
It’s so complicated; makes it so hard to breathe
With having this dastardly pulmonary hypertension disease.
Shortness of breath are symptoms at first
And sometimes it feels like your heart just may burst.
That weight in your chest, fast heart beats oh my
And walking too fast may just make you cry.
Some may get dizzy, or maybe pass out
Some are so tired - what’s that all about?
Some cannot work and don’t understand why
With little exertion they falter not fly.
Some have edema, that swelling so bad
Retaining that fluid just makes one so sad
Some may have chest pain and may have blue lips
This disease is too serious and needs to be nipped.
Some may have Scleroderma, Sleep Apnea or HIV
Lupus, Raynaud’s Phenomenon or maybe COPD.
There can be some causes or no cause at all
That’s when our ph doctors need to make the right call.
We cut back on salt, smaller portions for meals,
Nutrition’s important and helps us to deal,
We deal with life changes a whole new life style
Remember it’s doable – we’ll be here a while.
Many will ask when not feeling too well
How do I cope, how do I dwell?
Do not despair and let me just say
There are treatments out now – with more on the way
With hope and with faith we have a good chance,
To fight this disease and maybe then dance. 
Too many doctors; some specialist too
Do not understand what this ph disease can do
Luckily though and I praise God on high
There are ph doctors and nurses who do know the why
They treat us with wisdom and caring that shows
I thank them so much and I just hope they know.
They schedule those testings they start off real slow
An echo and blood work and others you know
A six minute walk, many PFT’s, oh gee
We scurry, we’re dazzled, we come then they see.
You may have a CAT scan, a bron-chos-co-py too
And there could be several others they make ask of you.
And then the right heart cath the gold standard of all
This proves the diagnosis is proper – they made the right call.
Some take an oral an inhaled or such
Some with IV’s and more, oh, oh so much.
Revatio, Adcirca, Letaris, Tracleer,
Ventavis, Tyvaso are a few that are here.
Then Veletri, Remodulin or Flolan may do
And some of these meds are almost brand new.
A hose in the nose; a tube in the chest
We struggle; we strive and hope for the best.
It is very doable this dastardly disease
With research abounding, there’s hope – so let’s breathe
Those researchers out there, those researching now
How can we help you, with what and the how.
We’re counting on you to brighten our life
You give us more hope to end all this strife.
We’ll give you some blood or whatever you need
And hope for a cure of this dastardly disease.
The cost of these meds is abhorrently high,
We suffer, we struggle, oh my how we sigh.
Some insurance companies won’t give us a dime
The government too in their wisdom declines
Then say they will help – but they have special rules
Most are careless and thoughtless and actually cruel.
There are specialty pharmacies and pharma reps too
With guided persistence they know what to do,
They tell all those doctors those specialists out there
About the ph meds; how they need treated with care.
Some have special nurses and advocates now
Who teach the new patients the why, what and how.
They treat us so special it’s learning one on one
They do have support for us, their work’s never done.
There’s a ph community it spreads far and wide
We meet in some chat rooms and support groups with pride.
I’ve made many phriends and I value them well
Unfortunately though, and I do have to tell
I’ve lost ooh too many, that hurts thru and thru
This dastardly disease can do that to you.
With our phamily support system we’re able to cope
We share with each other, there is always hope.
Hope for a future, hope for a life
Hope we’ll endure without too much strife
Although it’s not cancer the symptoms may be
As bad, sometimes worse than that horrid disease.
PH is progressive and can cause us much pain
We must not let fear grip us, there’s still much to gain
As mentioned before and remember this now
Pulmonary Hypertension is doable – we’ll be here a while.
Let’s take a deep breath; so slow if you please
It can strengthen those lungs with this dastardly disease
In through your nose and out through your lips
Slow is the key – please remember that tip.
And last but not least, remember to smile
As smiles are contagious you see
And when you feel down; and bring on a frown
Turn that frown upside down just for me
Smiles make us happy and will help us cope
With having this dastardly pulmonary hypertension disease. )
A little bit about Merle: As a PHA Helpline/Support Line volunteer, a PH Mentor, an advocate, a chat room moderator and leader of three PHA support groups (Mercer Area, PA; Cleveland Area, OH; and Pittsburgh, PA) Merle has exhibited unyielding dedication to the PH community. In support of the 2010 Path to a Cure Mt. Kilimanjaro climb, Merle helped organize a Unity Walk with her Pittsburgh, PA Support Group earlier this year. In February 2010, she helped raise awareness of pulmonary hypertension and heart transplantation at and in a ballet at the Byham Theater in Pittsburgh. This past September, the Cleveland Area Group had their 4th Annual Walk and Roll to raise funds for research and awareness for Pulmonary Hypertension. Merle is a tireless advocate and lobbyist for the PH community, and has reached out to government leaders from a local to a national level and she doesn’t care which state it involves. If a pher needs help, she is there for them. This past May Merle was asked to speak at a luncheon group the day before the Ohio primary. With that presentation to the UAW, she was able to mail over 200 signatures to each Ohio Senators about S 2803 and also letters to 5 Congresspeople about HR 1030. She is passionate about being a face for the PH community, and has appeared on television and radio in the Pittsburgh and Youngstown-area on many occasions, as well as featured in numerous Pittsburgh, Sharon, Cleveland and Akron-area newspapers. Her boundless energy, enthusiasm and caring spirit make her a true asset to the PH community.
With this passion and enthusiasm Merle was awarded PHA’s 2010 Outstanding PH Citizen which was presented at the 9th International Pulmonary Hypertension Conference and Scientific Sessions: “Riding the Wave” June 25th – 27th 2010 in Garden Grove, CA. Although she was unable to accept the award in person, arrangements were made and it was re-presented by a member of the Board of Directors and now sits proudly on her living room mantle.
Diastolic Dysfunction
Left Ventricular Diastolic Dysfunction (LV DD) is a very common cause of shortness of breath (dyspnea). It is far more common than Pulmonary Arterial Hypertension which is a disease characterized by increased pulmonary artery pressures caused by increased pulmonary vascular resistance (PVR). In contrast, LVDD can cause an increased pulmonary artery pressure but frequently is present in patients with normal pulmonary vascular resistance. Of patients who have a Right Heart Catheterization (RHC) for evaluation of possible PAH, 2/3 to 4/5 of patients will be found to have diastolic dysfunction as the primary abnormality leading to increased pulmonary pressures.
This is an important reason, if not the main reason, why all patients suspected of pulmonary arterial hypertension have to have a Right Heart Catheterization to confirm the diagnosis since using PAH medications in patients with uncontrolled LV DD is frequently harmful at worst or not helpful at best.
Background
The left ventricle of the heart is a muscular pump that pumps blood through muscle contraction and then fills either as a result of left atrial contraction (normal situation) or just as a result of blood flowing downstream from the right heart and lungs (atrial fibrillation). So far as the Left Ventricle (LV) is concerned, this is a passive process as the LV doesn’t pull blood into itself. In a normal person, the LV during the diastolic or relaxation phase of the heart beat is a compliant structure that can normally be filled easily with very little driving pressure. In fact, in a normal person, a pressure as low as 5 mm Hg can be sufficient to fill the LV. This pressure can be measured directly as the Left Ventricular End Diastolic Pressure (LVEDP) during a Left Heart Catheterization or indirectly as the Pulmonary Capillary Wedge Pressure (PCWP) during a Right Heart Catheterization. This is a measurement taken while the mitral valve is open and blood has stopped flowing from the Left Atrium to the Left Ventricle but before the Left Ventricle starts to contract. As there are no valves between the pulmonary veins and the left atrium this pressures is transmitted back through the pulmonary venous system toward the pulmonary capillaries and alveoli.
Diastolic Dysfunction
In patients with diastolic dysfunction, the left ventricle is abnormally non-compliant meaning that it takes more pressure than normal to deliver a normal stroke volume into the relaxed LV. In a euvolemic patient, most would consider an LVEDP or PCWP greater than 15 mm Hg to be abnormal though in a hypovolemic patient, an LVEDP or PCWP less than 15 mm Hg could still be abnormal and be indicative of diastolic dysfunction. Non-compliance of the LV could result from hypertrophy of the LV muscle wall such as might occur from long term hypertension though it sometimes occurs due to genetic factors or some feel, even as a result of ischemia that may be small-vessel ischemia. Additionally, elevations of filling pressures and a reduction in effective LV compliance can occur with LV systolic dysfunction where the residual volume of the LV is elevated at the end of systole.
Effect on the Lungs
When the LVEDP or PCWP exceeds about 20 mm Hg most patients will begin to develop pulmonary edema as the hydrostatic pressure can cause fluid to cross the alveolar capillary membrane resulting in ventilation-perfusion mismatching and shunting in the lung and this will result in hypoxemia and dyspnea. Eventually this can progress to result in Right Ventricular failure (as evidenced by an increased Central Venous Pressure (CVP) and lead to edema elsewhere in the body even to the point of causing recurrent pleural effusions in more severe cases.
What makes LV DD worse?
Anything that increases LV muscle tone can aggravate diastolic dysfunction. The most common causes are uncontrolled systemic hypertension. Hypertension to some degree frequently occurs as a normal result of exercise and in patients with diastolic dysfunction, trivial exercise can worsen LV DD enough to raise a marginal LVEDP/PCWP into a range causing symptomatic pulmonary edema, hypoxemia, and dyspnea. Tachycardia can aggravate diastolic dysfunction as can systolic heart failure. In patients with pulmonary arterial hypertension that is severe there can be inter ventricular coupling where a grossly enlarged Right Ventricle can push the intraventricular septum into the LV thus further compromising the LV’s ability to fill. Finally it is theorized that small vessel ischemia can increase LV muscle tone. Elderly patients frequently have some degree of diastolic dysfunction as a perhaps normal part of aging. Patients with morbid obesity and particularly uncontrolled sleep apnea or end stage renal disease also frequently have significant LV diastolic dysfunction. There are likely other humoral factors at play that have yet to be fully characterized as well.
How is diastolic dysfunction diagnosed?
A heart catheterization is the gold standard but usually must be combined with doppler echocardiography to help evaluate other causes of increased LVEDP/PCWP pressures such as mitral valve disease. LV DD is suspected in patients who clinically have left heart failure with a normal or frequently increased LV ejection fraction. The presence of recurrent transudative pleural effusions may also be a sign of diastolic dysfunction as are excessive diuretic requirements in patients who do not have significant LV systolic dysfunction.
How is diastolic dysfunction treated?
There are currently no medications with FDA approved indications for treatment of LV diastolic dysfunction. That said there are things you can do. Most important is to make the diagnosis. Once this is established, hypertension must be controlled. Diuretics can help to a point but excessive diuresis tends to worsen renal function and can even cause hypotension. If the LVEDP is high it’s frequently because the LV needs this much pressure to be filled. If the LVEDP is lowered excessively in a patient who is not volume overloaded then one would expect the stroke volume to fall and the patient’s cardiac output and perhaps blood pressure to fall as well. Most physicians treating LV DD feel that avoiding excessive tachycardia is helpful by increasing LV filling time. Calcium Channel blockers and Beta Blockers have been tried to decrease LV muscle tone and this is a reasonable theory though results are of limited efficacy in practice. Treating other aggravating factors such as obstructive sleep apnea, hypoxia, and obesity can be helpful.
Future directions
There is some limited evidence that Ranexa (Ranolazine) can help improve LV compliance and can lower the LVEDP or PCWP in patients with LV diastolic dysfunction but as yet there are no completed randomized placebo controlled human trials demonstrating significant benefit. Such therapy has to be considered both off label in that the drug is approved only for angina and experimental since there is so little human data. A Google search on “Ranolazine” and “diastolic dysfunction” will yield many links on the current state of evidence for use of Ranolazine in diastolic dysfunction. There is a single-site clinical trial staring at Boston University and another in Europe to better evaluate this potential new indication.
In our experience with off-label use of Ranolazine for LV diastolic dysfunction (based on about 40 patients treated) we have found that approximately 1/3 of patients appear to experience good improvements in exercise performance and sometimes hemodynamic parameters within 4-6 weeks of starting therapy while about 2/3 don’t see much early difference. The mechanisms of how Ranolazine may work in this disease are not totally clear and as time passes one would expect other similar agents to be developed that may be better targeted for diastolic dysfunction. It’s almost certain that LV Diastolic Dysfunction is more than one disease entity and one can theorize that there is one group with relatively fixed disease related to hypertrophied muscle while another more drug responsive group has diastolic dysfunction based on things that can change such as ischemia or hormonal / humoral factors.
Donald Elton, MD, FCCP
Lexington Pulmonary & Critical Care
Lexington, SC
http://LexingtonPulmonary.com
How to choose a pulmonary HTN doctor
Now more doctors and patients are aware the disease exists and many more patients are found who are suspected of having PAH and major medical centers no longer have the capacity to screen and treat all of these newly suspected PAH patients.
One common problem is that over 66% of patients suspected of having PAH really have other conditions such as left heart disease (particularly a condition called Left Ventricular Diastolic Dysfunction) that can mimic PAH but that are actually worsened if treated with PAH medications.
Doctors who finished their training before about 2000 will have had little or no useful training in diagnosing or treating PAH and to keep up must have obtained most if not all of their training and experience in PAH diagnosis and treatment after completing their formal residency and fellowship programs.
PAH is a hot area of research and in the last 10 years or so we’ve gone from a single FDA approved therapy to now having 10 approved therapies with many more in various stages of development. Unfortunately, most pulmonary and cardiology doctors have been far too busy to develop the knowledge and skills required to properly screen and treat patients with this still relatively rare disease.
What is a patient to do? There are some sources that can help. One is the Pulmonary Hypertension Association
http://phaassociation.org
They have lots of information for patients, caregivers, and physicians about PAH and they also have a searchable doctor directory where you can find a doctor who has an interest in and experience in diagnosing and treating PAH. Many doctors also post information about their practices so you can get a feel for the volume and complexity of patients they treat.
Find a Doctor who treats PAH
If you find a doctor in your area you’d like to consider seeing you will want to ask a few questions to help evaluate their capabilities:
1. How long have you been involved in treating PAH patents?
experience is good
2. How many patients do you have on PAH specific therapy?
doctors treating fewer than 5 or 10 patients are probably dabblers and not really committed to this specialty area
3. How many patients have you treated with PAH specific oral agents, inhaled agents, and parenteral agents?
you want a doctor who can use any or at least most of the available agents when needed
4. Do all of your patients on therapy have to have a Right heart catheterization before starting treatment?
if they answer no then you need to keep looking as a Right heart cath is standard of care for PAH diagnosis
5. Do you participate in clinical trials?
if not then you won’t have the option of using new agents for PAH before they are FDA approved
6. How many doctors will I be seeing?
If the group is too large you may have trouble getting to know or getting known by anyone and spreading the patients around too far within a group may limit how much experience any one doctor in the group can get in treating the disease
These are a good start toward evaluating who should evaluate you for PAH or other conditions that can be easily confused with or accompany PAH. After all of the above you have to meet and establish a comfortable working relationship with your treating physician.
Our Pulmonary Hypertension Center
We also offer participation in several clinical trials to assure that our patients can receive the latest in State-of-the-art care right here in the Columbia/Lexington area that used to be available only at major medical centers.
As of today (July 23, 2011) we are actively following about 200 patients with known or suspected pulmonary hypertension.
We have the following number of patients on the various approved therapy for pulmonary hypertension:
Tracleer (bosentan) 22
Letairis (ambrisentan) 24
Revatio (sildenafil) 5
Adcirca (tadalafil) 15
Ventavis (iloprost) 5
Tyvaso (treprostinil) 6
We are currently recruiting patients for the following clinical trials related to treatment of pulmonary arterial hypertension:
COMPASS-2 study - This is a drug study sponsored by Actelion Pharmaceuticals testing the combination of sildenafil and bosentan for treatment of Pulmonary Arterial Hypertension.
For referrals call our office at 803-520-5100 or send email to delton@lexpcc.net.