Printer Friendly

A cardiac patient is sliding into heart failure as opportunities to turn things around are missed: how she found her eventual road to recovery.

Dilated cardiomyopathy (DCM), atrial fibrillation (A-fib), and orthostatic intolerance (01) appear to run in our family. However, we didn't realize that there might be a genetic predisposition as Mom started sliding into heart failure, and we started a search for answers.


Mom seemed to be in pretty good shape for her age, 61, other than a history of frequent respiratory infections. In May, an X-ray taken for suspected pneumonia showed her heart to be within normal limits. She was starting to develop hypertension, so in June she was started on a calcium channel blocker.


Exactly one year later, despite another X-ray showing her heart to be within normal limits (WNL), our family doctor heard a murmur and referred her to a cardiologist. An echocardiogram (echo) showed moderate left ventricle (LV) enlargement and a left ventricular ejection fraction (LVEF) of 30% to 35%. (The LVEF measures the percent of blood being pumped out of the left ventricle. 55% to 70% is considered normal.) A month later, a cardiac catheterization (cath) showed moderate to severe left ventricle dysfunction. Her vessels were "pristine."


A month before last year's cardiac cath, hydralazine had been added to her medications, and now her calcium channel blocker was switched to atenolol, a beta blocker selective for beta-1 adrenergic receptors, which primarily affects pulse. Afterward, her pulse was good, 68 to 78, but her blood pressure was still mild to moderately high. Although we could not find the echo referred to, the cardiologist's notes stated that an echo still showed LV dysfunction. In October, a calcium channel blocker was again added back into her regimen along with the other two medications.


On the three medicines, an echo showed a LVEF of 60%, which was good, but she had mild dilation of the left atrium (LA) and moderate concentric hypertrophy of the left ventricle.

During that spring and into the summer, she started developing new symptoms, particularly weakness in her arms. She described barely being able to pour milk for her cereal.

In May, they tested her erythrocyte sedimentation rate (ESR; a.k.a. sed rate), and it was 32. To me, what she described sounded like the symptoms of an autoimmune disease, but given the fact that she fell outside the normal age of onset for many of them, I wanted them to look at the possibility it was being triggered by one of her medications, but Mom didn't feel comfortable telling her doctors what to do.

Despite a positive antinuclear antibody (ANA) and elevated sed rate (58) and rheumatoid factor (RF) in June and an ANA of 1:640 in August, it wasn't until November, when her sed rate was still 27 despite prednisone, that they decided it was most likely a reaction to one of her medications, probably hydralazine, and had her immediately stop the hydralazine and atenolol and continue on a calcium channel blocker. About this same time, they started down titrating the prednisone, although it would take almost a year on prednisone before the positive ANA was resolved.


One morning 3 months later, she was sitting on a lounge chair with her feet up, and she just passed out. A hospital EKG found sinus tachycardia, diffuse nonspecific ST and T wave changes, and a nonspecific intraventricular conduction delay. An echo showed a LVEF of 50% to 55% and mentioned only mild thickening of the mitral valve leaflet. Her carotid arteries were OK. Creatine kinase was 24, troponin was less than 3, and a test for diabetes was negative, which meant that the episode wasn't caused by a heart attack or a hyperglycemia-triggered arrhythmia.

When I later looked through Mom's medical records, they showed that after stopping the beta blocker, her pulse at her pulmonologist's office had jumped from 78 (October 2002) to 117 (November 2002) and 114 (January 2003).


It had been over a year since the loss of consciousness episode, and the pulmonologist's records continued to show that her pulse was elevated: 110 (January 2004) and 121 (April 2004). No one seemed to notice, and by the end of the year, she was in trouble. In November, an X-ray showed mild to moderate heart enlargement. In December, another X-ray showed, in addition to the enlargement, "Some slight central pulmonary vascular congestion is noted on the current examination. The findings suggest borderline congestive heart failure."

An echo done the next day showed LV enlargement and a LVEF of 25%. The cardiologist wrote to Mom's primary doctor, "She [Mom] has a markedly dilated, very poorly contractile ventricle, with overall severe left ventricular dysfunction."

Rather than look back through Mom's medical records to see if there might have been a pattern, if any of her medications might have contributed to that positive echo done in February 2003, which showed a LVEF of 50% to 55%, the cardiologist questioned its validity, writing: "In retrospect I wonder if this was actually accurate."

Two days later our family doctor, seeking a second opinion on treatment options, had Mom in to see another cardiologist, who ran another echo, which basically had the same findings including a LVEF of 20% to 25%. He had nothing new to offer.


After Mom saw a third cardiologist with no improvement in her echo, our family doctor strongly suggested to me that we take her to Mayo or someplace similar.

In trying to find the right doctor and educate myself as well, I immediately started reading the medical studies on DCM and started putting together Mom's medical records. I wanted to chart her records for the cardiologist, knowing that our time with him would be limited.

Reading the studies along with Mom's medical records was like putting together the pieces of a puzzle. The hydralazine reaction had been a huge clue in that the risk of a reaction was associated with multiple factors which included female gender, according to some studies; slower activity of the enzyme N-acetyltransferase 2 (NAT2), that breaks down hydralazine; and carrying human leukocyte antigen (HLA)-DR4. (1,2) HLA-DR4 had also been associated with an increased risk of developing the other diseases that ran in our personal and/or family medical history: DCM, Hashimoto's thyroiditis, and Hurthle cell thyroid tumors. (3-6) I asked our doctor if Mom and I could be tested for HLA-DR4, and we were both positive.

DCM had multiple potential causes, but one team had found a strong association between HLA-DR4 positive DCM and having beta-1 adrenoceptor autoantibodies, "72% of the HLA-DR4 dilated cardiomyopathy patients had anti-beta-receptor antibodies compared to 22% HLA-DR4-negative patients; conversely, 67% of the antibody-positive patients were typed as HLA-DR4 compared to only 10% of the antibodynegative patients." (3) It was thought that beta-1 adrenoceptor stimulating autoantibodies could lead to tachycardia and DCM and eventually to decreased beta-1 adrenoceptor expression or sensitivity and heart failure. (7-9) It was also thought beta blockers could reverse some of the abnormalities. (7-8)

Her medicines had been changed multiple times, but when I charted the results of the echoes and the medicines that she was receiving in the 6 months prior to each echo, a pattern seemed to emerge. She seemed better on the beta blocker, which she was not currently taking, and worse on the calcium channel blocker.

120 studies and 2 inches of medical records later, including the tachycardia that went unnoticed, I was convinced that Mom was on the wrong medicine and needed to be on a beta blocker. Despite her worsening echo results including LVEF, Mom's B-type natriuretic peptide (BNP) was not that far out of range 106 (range 0-100), which gave me hope that her condition might be reversible.

Mom's response? "I believe you. You were right about my reaction to my medicine, but I can't tell my Ivy league-educated cardiologist, 'My daughter thinks I am on the wrong medicine.'" Luckily, my mom's immunologist noticed that Mom was taking a calcium channel blocker and told Mom that, while she hesitated mentioning it, she thought that Mom was on the wrong medicine; she thought calcium channel blockers weren't suppose to be given in DCM. That gave Mom the push that she needed to go to our family doctor and argue for changing her medicine to atenolol, which he did.

We felt comfortable making this switch in her medicine knowing that in a month we had an appointment for Mom to see a cardiologist * at Baylor Heart Hospital in Houston, Texas. His name kept showing up on some of the most forward-thinking studies at the time. (10,11) They were about things that we were interested in. (11,12) While in Houston, they did a another cardiac cath and additional blood tests to make sure that nothing had been missed, asked to be sent her previous echoes, and reiterated that we had her on the right medicine and that calcium channel blockers were contraindicated in DCM. (13)

Within a year on the beta blocker and hydrochlorothiazide (HCTZ), Mom's LVEF improved, from an estimated low of 20% to 25%, to 45%; and the size of her heart responded favorably as well. Almost a decade later, she is still alive and in good health for her age, 76.

Looking back, I think that things could have been done differently. Her medications weren't reevaluated when new symptoms arose, the beta blocker wasn't down-titrated slowly as the PDR advises, her changes in pulse rate went unnoticed, symptoms were treated instead of diseases, and the echo done February 2003 (after Mom had been on all three medicines) appeared to be disregarded, written off as a mistake.

One of the things that doctors are less likely to be familiar with, which could have been useful, is the HLA tests. Testing for HLA-DR4 in female patients with DCM may help predict which patients may have a problem with hydralazine. (1-3) In one study, up to 73% of hydralazine-induced systemic lupus erythematosus (SLE) patients were HLA-DR4 positive, and, "If the slow acetylators treated with Hydralazine were analysed as one group, it was observed that all women with DR4 developed Hydralazine-induced SLE." (1) This test might spare other patients from going through what Mom did.

I first learned to read medical studies prior to Mom's getting sick when, after my own health problems, my aunt, a nurse anesthetist, handed me some studies and a huge medical dictionary, and said, "In the very least, you need to learn enough to make informed decisions. They're having you try things that appear to be making you worse." We had accomplished what she had hoped for and learned to make informed decisions.

* Ironically, the cardiologist from Houston has since became head of cardiology at the teaching hospital in the city where my mom lives. It is the same teaching hospital where my aunt got her nursing degree.


(1.) Batchelor JR, Welsh KI, Tinoco RM, et al. Hydralazine-induced systemic lupus erythematosus: influence of HLADR and sex on susceptibility. Lancet. 1980;1(8178):1107-1109.

(2.) Cameron H.A., Ramsay, L.E. The lupus syndrome induced by hydralazine: a common complication with low dose treatment. Br Med J (Clin Res Ed). 1984:289(6442):410412.

(3.) Limas G, Limas C. HLA antigens in idiopathic dilated cardiomyopathy. Br Heart J. 1989;62(5):379-383.

(4.) Martinetti M, Saalvaneschi L, Graziano G, et al. HLA polymorphism in the susceptibility or resistance to dilated cardiomyopathy. G Ital Cardiol. 1992;22(1):73-83.

(5.) Thompson C, Farid NR. Post-partum thyroiditis and goiterous (Hashimoto's) thyroiditis are associated with HLA-DR4. Immunol Lett. 1985;11(5-6):301-303.

(6.) Rigopoulou D, Martinez-Laso J, Martinez-Telio F, et al. Both class I and class II HLA antigens are thyroid cancer susceptibility factors. Tissue Antigens. 1994;43(5):281-285.

(7.) Magnusson Y, Wallukat G, Wangstein F, Hjalmarson A, Hoebeke J. Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. Circulation. 1994;89(6):2760-7.

(8.) Podlowski S, Luther HP, Morwinski R, Muller J, Wallukat G. Agonistic anti-beta 1-adrenergic receptor autoantibodies from cardiomyopathy patients reduce the beta 1-adrenergic receptor expression in neonatal rat cardiomyocytes. Circulation. 1998;98(22):2470-2476.

(9.) Omerovic E, Bollano E, Anderson B, et al. Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy. Autoimmunity. 2000;32(4):271-280.

(10.) Torre-Amione G, Kapadia S, Lee J, et al. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation. 1996;93(4):704-711.

(11.) Mann DL. Autoimmunity, immunoglobulin absorption, and dilated cardiomyopathy: has the time come for randomized clinical trials? J Am Coll Cardiol. 2001;38(1):184-186.

(12.) Dorffel WV, Felix SB, Wallukat G, et al. Short-term hemodynamic effects of immunoabsorption in dilated cardiomyopathy. Circulation. 1997;95(8):1994-1997.

(13.) Alves ML, Gaffin RD, Wolska BM. Rescue of familial cardiomyopathies by modifications at the level of sarcomere and Ca2+ fluxes. J Mol Cell Cardiol. 2010;48(5):834-842. doi:10.1016/j.yjmcc.2010.01.003.

by Laurie Dennison Busby, BEd

[C] 2014 Laurie Dennison Busby, BEd
COPYRIGHT 2016 The Townsend Letter Group
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2016 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Busby, Laurie Dennison
Publication:Townsend Letter
Date:May 1, 2016
Previous Article:Straight talk about heart failure.
Next Article:An integrative medical approach to reversing cardiovascular disease: practicing beyond the standard of care.

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters