Heart Failure, Infection, & a Medical Brick Wall
What I Did to Save My Father's Life--The First Time.
My father developed end-stage heart failure in his early 60’s, despite decades of top cardiology care. They said heart transplant was his only hope—They were wrong. Treating an overlooked infection permanently fixed his heart, averting the need for heart transplant. He passed away on 5/9/2021, 1 year ago today, at almost 90, may he rest in peace. This work is dedicated to my Dad. May it save someone you love.
Heart failure is the heart’s inability to ably pump blood. When the heart muscle chronically weakens, it’s called cardiomyopathy. Myocarditis describes acute inflammation of the heart—Sometimes also causing heart failure.
A major cause of disability and death, the many causes of cardiomyopathy include coronary artery disease, hypertension, and diabetes. But up to 50% of cases (75% when it’s in kids!) are “idiopathic,” of unknown origin. I dislike that word. It makes me feel like the medical profession is trying to compensate for its ignorance by using a lofty Latin-derived term to feel better about itself. Even worse, once that label is applied, the investigation into cause usually stops.
It doesn’t have to be this way. We have an astounding arsenal of accumulated medical knowledge—So why are treating physicians too often pervasively uniformed? Einstein said that we should make everything as simple as possible, but not simpler. That’s good advice. An example of making something simpler than it is would be to designate a case of cardiomyopathy as “idiopathic.” There’s an answer to every question—And some of those answers may help save the lives of patients who would otherwise suffer with, or die from, heart failure.
When evaluating patients with heart failure of unknown etiology, in addition to the important genetic and toxic causes not covered in this article, physicians also need to evaluate for infections. The infectious causes of cardiomyopathy are legion, but they usually don’t end up on doctors’ radar screens, with the exception of viruses—They’re the favored infections that get most of the street cred when it comes to heart failure. It’s not entirely undeserved—Many can cause heart muscle disease.
But doctors seem to be overly fond of blaming viruses when something is poorly understood. Viruses are presumed to be the most frequent cause of infectious myocarditis, a subset of which progresses to cardiomyopathy. But are they really? A study compared 40 healthy patients to 40 cardiomyopathy patients. Cardiac biopsies were analyzed by both electron microscope and polymerase chain reaction (PCR), a method to amplify DNA with which most of us are now familiar due to Covid testing. Viruses were found in 58% of both groups, but Lyme bacteria were only detected in cardiomyopathy patients:
“…prevalence of viral particles does not differ between subjects with preserved LV systolic function [no heart failure] versus those with DCM [dilated cardiomyopathy] and therefore suggests that the mere presence of a viral agent within the myocardium is not sufficient to establish a clear link with the development of DCM. In contrast, the presence of Bb [Lyme bacteria] was found only within myocardial samples of patients with DCM…”
Among viruses causing heart muscle inflammation, adenoviruses, enteroviruses, and parvovirus B19 are thought to be among the worst offenders because their DNA is often detected in cardiac biopsies from myocarditis patients. But when we look for these same three viruses in biopsies from myocarditis patients along with biopsies from a healthy control group, we see that these viruses may not be the driving factor in many cases of heart muscle disease:
“PVB [parvovirus B19] was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus…The detection of PVB in myocardial autopsy samples most likely represents a persistent infection with no or limited association with myocardial inflammation.”
So parvovirus B19 was the only virus whose DNA was found in diseased hearts, but it was found in the hearts of healthy people about 50% more frequently. I’m neutral on the observation of the higher rate of parvovirus DNA in healthy people—But wouldn’t it be ironic if the presence of parvovirus in the heart was protective?—I’m joking, but not entirely.
For example, some viral infections actually do benefit us—Everything from spurring on the evolution of our cognitive abilities and placentas, to helping provide resistance against HIV, smallpox, listeriosis, and cancers, and to helping improve our microbiomes—Truth can be hidden in the most surprising places.
Viruses can also be functioning as cofactors to other infections. Infections mesh with each other in strange ways—Lyme bacteria can bring Epstein-Barr virus (EBV), out of latency, inducing its replication in white blood cells. And as we’ve seen in MS, the association of EBV and MS only rigorously exists when EBV is acquired in adolescence to young adulthood, at an age when it can cause infectious mononucleosis, but not when infection occurs in early childhood. So in the case of MS, rather than the virus itself, is the mononucleosis immune response functioning as a co-factor to another infection? Research is too often focused on single infection or single immune response models that don’t represent what happens in real life. We’re tapestries, not individual threads.
And the cofactor relationship isn’t limited to other infections: For example, bleomycin is a toxic chemotherapy drug that can cause lung damage. Mice that are normally resistant to its effects succumb to more lung damage when they’re infected with a certain herpes virus. A similar two-hit scenario occurs with doxorubicin, a chemotherapy that can cause cardiomyopathy, and viral infections. Like I said, tapestries.
A partial list of viruses that can cause heart muscle disease includes:
Coxsackie (A, B)
Influenza (A, B)
Such muddy waters—Many of these viruses are ubiquitous in healthy people, rendering antibody tests less helpful. And as we’ve learned from Covid, viruses aren’t always clearly defined as fleeting or chronic. Many not typically thought to cause chronic infection can do just that, and having antibodies doesn’t prove persistence. Cardiac biopsies may help clarify which pathogen(s) may be causing disease, but only when the investigation is exhaustive—And even then, we run the risk of attributing cause to an asymptomatic infection.
Parasitic infections can also cause heart muscle disease, but in the US, parasites are ignored on a regular basis. It’s as if physicians here think that we’ve eradicated them all. We haven’t, and they’re not all rare: For example, more than 40 million Americans are infected with toxoplasma, as is 30-50% of the entire global population. For toxocara, US infection rates are 5% to 14%. Strongyloides infects up to 6.1% of Americans in rural areas and up to 46.1% of our immigrant populations. For the ones that can’t readily be acquired in the US, keep in mind that many residents were born in other countries, plus air travel has made the world a very small place—I remember a family of American patients I treated who got schistosomiasis after a quick dip in a lake while on vacation abroad.
Most American docs have a default mindset when it comes to locally acquired parasitic infections—That they can’t make us sick unless we’re immunosuppressed. But it’s not true. Although the immunocompromised can become sicker from many parasites, people with normal immune systems can also become quite ill from them—Even to the point of transplacental infection and disease. And let’s not forget that we’ve become a deliberately immunosuppressed society—From 2018-2019, 2.8% of the US population was intentionally immunosuppressed by drugs. And on top of everything else, parasites often don’t mesh well with bacterial infections—The immune response from one tends to cancel out the other:
“Interestingly, the responses induced by the extracellular helminths and those induced by the intracellular Mtb [Tuberculosis bacteria] are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infecting pathogens.”
Trypanosoma (Chaga’s disease)
Taenia solium (Cysticercosis)
Many routine bacteria can cause cardiomyopathy in the context of overwhelming sepsis, the body’s intense response to a massive infection. Rapidly dividing in a life or death race to outpace the immune response, they’re relatively easy to find by routine medical tests—That’s not the group I’m writing about.
I’m talking about the sneaky bacteria that medical science doesn’t really understand, but pretends to. Most of them evolutionarily ancient, they’ve been adapting to, and hiding from, our immune systems over eons. These bacteria grow slowly. Like a lion stalking its prey, they creep until they’re well positioned to attack. Different bacteria can infect us through different routes—Bug bites, respiratory transmission, sexual transmission, non-sexual body fluid contact, food-borne, and water-borne.
When treating a routine infection like strep throat, antibiotics don’t kill every last bacteria. They debulk the infection and allow the immune system to clean up the stragglers—But with an infection that can evade our white blood cells, the stragglers grow back into a full-fledged army. And to make matters worse, although some, like syphilis bacteria, are sensitive to antibiotics, many are antibiotic-resistant—Double whammy.
A partial list of slow growing bacterial causes of heart muscle disease includes:
Tropheryma whipplei (Whipple’s disease)
Francisella tularensis (Tularemia)
Coxiella burnetii (Q Fever)
The Eyes Can’t Be Open When the Mind is Closed
“exhibit low sensitivity.”
Yet despite problems in test sensitivity, in a study of heart failure patients awaiting heart transplant, 21% still had positive bartonella antibody tests vs. none of the healthy controls. The statistical difference for this finding was striking, with a p value of 0.002—But the discussion was almost entirely limited to concerns of bartonellosis getting worse after heart transplant, when patients are immunosuppressed:
“…post-transplant, as a consequence of immunosuppressive therapy, bacterial reactivation could result in a severe and disseminate bartonellosis that could compromise several organs.”
It’s the same myopic dogma as with US-acquired parasitic infections—That they don’t affect those with normal immune systems. But bartonella is known to be capable of causing fatal myocarditis and cardiomyopathy leading to heart transplant in the immunocompetent. Could bartonella could have been causing heart failure in these patients?
“: a competitive or noncompetitive recreational activity in which participants use a map and compass to navigate between checkpoints along an unfamiliar course (as in the woods)”
Running through unfamiliar woods is obviously a high risk activity for bug bites, a means by which bartonella is spread. Over more than a decade, one by one, these top athletes were dropping dead.
“During the period 1979-92, an increasing number of sudden unexpected cardiac deaths (SUCD) occurred in young, Swedish, male elite orienteers. Myocarditis was the most common diagnosis…Bartonella-induced silent subacute myocarditis, eventually leading to electric instability, caused the increased SUCD rate among the Swedish orienteers…”
Lyme is another important but frequently dismissed cause of heart muscle disease, also capable of causing fatal myocarditis or leading to heart transplant. In a study of 110 patients with dilated cardiomyopathy, 20% of these heart failure patients were found to have Lyme DNA in their heart muscles on cardiac biopsy—They were treated with antibiotics and their heart failure markedly improved. And most of these patients with documented Lyme cardiomyopathy had negative Lyme antibody tests. And none had stereotypical Lyme disease. In fact, a review of 8 studies revealed that Lyme antibody tests miss more cases than they diagnose. Umm…so how do patients get diagnosed if they fall through the cracks with insensitive Lyme testing and failure to meet an inaccurate stereotype of the disease? Good question—It’s part of why Lyme remains one of the most longstanding and bitter David vs Goliath medical debates in history.
Thread, Meet Tapestry
Although some microbes can produce disease on their own, many play only partial roles. The total impact of the multitude of common infections we carry is the infectious burden. When it’s powerful enough, it becomes capable of overwhelming the immune system. For example, patients with Chaga’s disease and bartonella more frequently have positive bartonella blood cultures, suggestive of worse disease. TB patients co-infected with toxoplasmosis demonstrated evidence of more severe TB. Strongyloides infection is made worse by co-infection with HTLV-1, a retrovirus related to HIV—but it’s not made worse by HIV itself. And researchers have shown that a weighted metric of the following 5 common infections: Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2, correlated with carotid artery atherosclerosis:
“A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness…”
And I don’t think that heart muscle disease is dissimilar. Each of those five infections carries with it the possibility of vascular inflammation. But as individuals, we have innumerable hereditary and environmental factors that dictate how our immune systems respond to these provocateurs. In one person, it may only take one of these infections to cause vascular disease. In another, the threshold may be three infections or more.
My Dad’s Story—It Could Happen to Anyone
My father had what was empirically diagnosed as a viral meningitis when I was a little kid, but they never found a virus. They just told him to get some rest and he’d be fine, and he did slowly recover.
Meningitis means inflammation of the lining around the brain, and it’s most often caused by an infection. There are two general categories of meningitis, but their names are misleading—Bacterial and aseptic meningitis. Bacterial meningitis can be a rapidly fatal illness, and survivors frequently have long-term neurologic damage. It’s caused by pyogenic bacterial infections. Pyogenic bacteria are rapidly growing and our bodies produce pus in response to them.
When I think of the word “pus”, I think of how my mother reacted when I told her I decided to go to med school:
“Are you crazy? You’re a Wharton grad, you have a great job on Wall Street. Are you going to be happy surrounded by phlegm and feces and pus all day?”
Not the typical reaction when a son tells his Mom he’s going to be a doctor, but she eventually came around. Although to this day, phlegm, feces and pus are some of my least favorite words. But I digress.
My Dad had the less dangerous aseptic meningitis, which is not caused by pyogenic bacteria. Aseptic meningitis can be caused by viruses, non-pyogenic bacteria, fungi, or parasites. In general, non-pyogenic bacteria can be thought of somewhat synonymously with the mysterious ones mentioned earlier.
Shortly after that, he developed his first bout of atrial fibrillation, a common heart rhythm disturbance. It only lasted a few hours, but would recur every month or so. He saw several doctors who assured him that this was a benign and non-progressive condition. They were wrong. Over time, his atrial fibrillation became more frequent and the episodes last longer. After several years, he developed chronic atrial fibrillation. Over a decade later, he developed heart failure. He was seen by the top cardiologists at the top teaching hospitals in New York City. And under their watchful eyes, while he compliantly took their best medicines, he declined to the point that without their recommended heart transplant, his life expectancy would be less than six months.
Even in the early 1990’s, Lyme bacteria had been be isolated from the heart muscle of patients with cardiomyopathy, and it had been proven that antibiotic treatment could reverse the condition. So, fresh out of having done Lyme research at Yale during residency, and knowing far less than I thought I knew, I asked his cardiologist the simple question— Could my Dad’s cardiomyopathy be caused by Lyme? His answer began with an eye roll, never a good sign. It was followed by a mini-lecture, an even worse sign. He told me that without a history of rash, arthritis, or Bell’s palsy, he didn’t have Lyme and refused to even test him.
My Dad’s life was at stake and I felt that his famous doctor’s arrogance was blinding him to a proper risk-benefit analysis, but he wouldn’t take anything I said seriously. I was a young punk with a full head of hair who looked like I should be working at the mall. Undergoing heart transplant, in my view, was far more risky than treating my Dad for Lyme. I won’t sugar-coat it—Treatment was a complicated three year long process, but the result was worth it. His heart function fully recovered and he never needed that heart transplant. In fact, he never had heart failure again for the rest of his long life.
ZeroSpin is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.
Thank you for taking the time to consider my thoughts. I so appreciate your subscription to this newsletter (and am extraordinarily appreciative of those generously opting for the paid subscriptions!!). If you like what you’ve read here today, please share it with your friends.
Disclaimer: None of my posts contain medical advice. These posts are intended for purely informational purposes only. Please check with your doctor before undertaking any course of treatment.