Arnold Meshkov, MD

Arnold Meshkov MD. is a cardiologist, heart health expert, and was a Professor of Medicine at Temple University School of Medicine until 2015 when he returned to private practice. He is Board Certified in Internal Medicine, Cardiology, and Echocardiography and has lectured on a broad range of topics in cardiology and bioethics. Dr. Meshkov served for many years as the Chairman of the Ethics Committee at Temple University Hospital and was the coordinator of Cardiology Grand Rounds, a weekly lecture series at Temple. 

It is surprising how little data are available telling us the incidence of asymptomatic, or “subclinical” atherosclerosis in the general population. Atherosclerosis imaging, by cardiac catheterization or noninvasive testing, is usually performed in patients with symptoms suggesting coronary artery disease. But just recently, the result of a large study of over 30,000 Swedes ages 50-64 was published in 

 Using a coronary artery calcium score and a CT angiogram of the coronary arteries, the study found that slightly over 40% of people had “silent” coronary artery atherosclerosis. The good news was that only about 5% had a significant blockage.

Prevention of heart attack and stroke are now commonplace, especially in those who had an acute cardiovascular event. More people are benefiting from “primary prevention” when they have multiple risk factors and an elevated blood LDL and cholesterol levels. But more needs to be done to identify those who have a mild degree of atherosclerosis, as the recommendations regarding treatment with statins will change if atherosclerosis is demonstrated by imaging. A blood test can express risk, but imaging atherosclerosis will likely have a significant psychological effect on both the patient and doctor, and improve compliance with long-term use of medication i.e., statins.

The history of the heart attack has had long periods of time of not knowing much of anything about its cause, treatment, and identification of atherosclerosis before someone had a myocardial infarction. Too often many did not survive. From the time of William Heberden’s report in London in 1776 about a group of patients with “angina pectoris,” 140 years passed until Nikolai Anichkov in Russia proved that atherosclerosis was due to cholesterol deposits, and in the same time frame William Herrick in the US described the multiple manifestations of coronary artery disease, with the new finding that in some patients, long term survival is possible.

The ability to determine the presence of atherosclerosis as a cause of chest pain and risk for a myocardial infarction has faced enormous challenges. Beginning in the 1930s, studies began using exercise to try to see it would cause EKG changes of ischemia. The results were not impressive, and even the Master “two-step” developed in the 1940s had such limited accuracy that it would be difficult to have the results published today in a peer-reviewed journal.

The work continued, first with the development of the motorized treadmill by Robert Bruce, MD, of the University of Washington in the late 1960s, followed by the ground-breaking work of the first “nuclear” cardiologists like Barry Zaret, MD, of Yale. Imaging as well the EKG changes dramatically improved the statistical sensitivity and specificity for significant coronary artery atherosclerosis. But even these two major changes in diagnostic testing proved to be of minimal predictive value for cardiac events in the general population.

At the present time, there are two other imaging technologies that allow for the noninvasive of atherosclerosis. First came the coronary artery score invented by Arthur Agatston, MD, in the 1980’s. This very simple imaging technique is shown to predict cardiac risk very well, with higher levels of coronary artery calcium indicating more advanced atherosclerosis. Equally important, a “0” calcium score indicates an excellent prognosis for the next several years.

In more recent years, CT angiography of the coronary arteries has developed into a more mature technology, initially overcoming the technical difficulty of creating CT images of the heart with a heart rate over sixty beats per minute. Although the problem of image “blooming” from areas of calcification can still be a problem, this modality has also proven its worth regarding prognosis, and assisting decision making between medical therapy and cardiac catheterization, with a final decision of angioplasty or coronary artery bypass surgery.

The use of these technologies will hopefully advance the diagnosis of atherosclerosis in the general population. We know that this disease begins at a young age and is too often progressive without treatment. These tests may lead people to the conclusion that a better diet, more exercise, and many times medication will reduce the risk. It may take decades to see if these two tests lead to better outcomes. Let’s hope the insurance companies and Medicare agree to let us use them.

Bergstrom, G, Perrson M, et al. Prevalence of subclinical atherosclerosis in the general population. 

Chasing the Widowmaker – The History of the Heart Attack Pandemic, 

2021 KoehlerPublishing, Virginia Beach, Virginia. Chapter 6: Divining the Signals: The Creation of the Stress test; Chapter 18: Stopping Time: The Radioactive Heart Images.

Articles

Arnold Meshkov, MD, explores how discoveries and the advent of new technologies have influenced diagnosis of atherosclerosis throughout history.

Is Silence Golden? The Hunt for Hardening of the Arteries

There is that well-known saying that you’re entitled to your own opinion, but not your own facts. The COVID-19 pandemic that has rocked our world has engaged some of the brightest among us to use the methods of science to try to reign in this horrible virus. Vaccinations have been used to combat human disease since the 18th century when the Englishman Edward Jenner developed a vaccine to prevent smallpox. 

Almost none of us who are alive have seen smallpox—it 

 a very deadly disease, and even survivors were often left them with life-altering facial scars. Why don’t we see smallpox? 

BECAUSE VACCINES HAVE ERADICATED THE DISEASE

! Prior to worldwide vaccination, there were 300 MILLION cases in the 20th century.

Still, there are the doubters worldwide, for reasons that truly escape me. When the pharmaceutical companies went to work on vaccines, they used the very latest in biochemical and molecular biology techniques that rapidly accelerated their ability to produce vaccines.

At the end of the last year, Pfizer and BioNTech together reported their results of a multinational trial in the New England Journal of Medicine. The study involved over 43,000 people in the US, Brazil, South Africa, and Turkey. Half of the group received two vaccine doses separated by 21 days, and half were just left to live their normal lives. The vaccine, named BNT162b2, is a lipid nanoparticle that contained the RNA code for the “spike protein” of the COVID-19 virus, so that when it entered the cells of the body, the foreign RNA would get into the cells and start to make numerous copies of not the entire virus, but just the “spike protein.”

When the RNA-manufactured spike protein gets into the bloodstream, the white blood cells recognize it as a foreign invader, and chew it up. Then, they are primed to attack any new “spike proteins” they encounter – like from a viral infection of Covid-19. The white cells have “immunologic memory.”

Do we need to know anything else about the effectiveness of the Pfizer/BioNTech vaccine? Well, maybe. How about that there was only ONE case of serious Covid-19 in the vaccine group. The major side effect was fatigue – seen in less than one percent of vaccinated patients.

The new vaccines using the RNA code will prove to be a revolution in not just vaccine production but in so many other uses in medicine. The historical track record of vaccinations is a triumph of science and medicine.

The previously mentioned Dr. Jenner discovered that using a strain of cowpox virus, a bovine disease that does not cause human disease, was able to protect humans from smallpox. Later in the 19th century, Louis Pasteur was able to cure rabies, a fearful disease caused by a virus that attacks the central nervous system. How did he do that? He infected rabbits with rabies, putting himself and all of his lab workers at great risk, then sacrificed the rabbits, and dried out their spinal cords. He didn’t even know that rabies was a virus, but he knew that the disease attacked the nervous system. He then ground up the spinal cords, put the material into a solution, and injected it into a young boy who had been bitten by a rabid dog. Pasteur’s treatment worked and the world was changed forever.

By the 20th century, scientists and doctors had two examples about how “attenuated” viruses, those of cowpox and rabies, could safely stimulates the human immune system of white blood cells and antibodies to protect against many of the great ravages of human history. Let’s look at the scorecard:

 – first developed in the 1940’s, and newer vaccine using DNA technology introduced in 2013. In the 2019-2020 flu season, the vaccine prevented an estimated 7.5 million infections, 105,000 hospitalizations, and 6,300 deaths

 – poliomyelitis is a virus that also attacks the nervous system, leading to death and even in recovery often severe disability, especially in children. I am old enough to remember the Salk vaccine “sugar cube” given on Sunday mornings in my elementary school. Polio is GONE from the United States now.

 the yellow fever virus caused epidemics in cities for centuries; now gone in most parts of the world because of vaccines and measure to stop mosquitos, the carriers of the virus. Yellow fever raged through the workers on the Panama Canal, and it was the public health work of Walter Reed that saved that project.

 – the vaccine has prevented 2-3 million cases, 50,000 hospitalizations, and 500 deaths EACH YEAR in the United States. Measles in far more contagious than Covid-19, and outbreaks have occurred in the US in recent years in communities that have not vaccinated their children.

 – a nasty virus that causes severe gastrointestinal symptoms, dehydration, and death if not treated. A vaccine for this disease has thwarted a disease that once killed 500,000 people worldwide each year.

 – a virus in children that was once a common cause of deafness; now gone in vaccinated people

– a form of the measles virus. Usually a mild disease in adults, but a major cause of severe disability in children whose mothers were infected while pregnant, as well as spontaneous abortion. Also, now almost gone in vaccinated women of childbearing age.

 – this virus that attacks the liver has several forms, and both hepatitis A and B can be eliminated with vaccines.

The Covid-19 vaccines will enter this growing list. Tragically, epidemics have killed far more people over history than all of the wars combined. There is more work to be done, and not all viruses can be stopped by vaccines. There is still no vaccine for the AIDS virus, in spite of three decades of research, but there is an effective medication to control the disease. I wish there was a vaccine for the “common cold,” but there are too many different viruses that cause this disease.

We, as a society, need to reflect on our obligation not just to ourselves but to our families, friends, and the rest of our community. There has been a perversion of the idea of the sanctity of the belief in individual freedom by too many people. Your freedom does not entitle you to harm others. Vaccination against Covid-19 is not optional if we want our world to return to “normal,” and the scientific data are there to prove the case.

Polack F., Thomas S. et al. The safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine 383:2603-2615, December 31, 2020.

Desmond, A, and Offit, P. On the shoulders of giants – from Jenner’s cowpox to mRNA Covid vaccine. New England Journal of Medicine 384:1081-1083. March 25 2021.

Arnold Meshkov, MD, discusses the rollout of the COVID-19 vaccines and gives perspective on the history of how vaccines have been used to help eradicate pandemics. 

A Picture is Worth a Thousand Words! An Anti-Vaxxer's Nightmare, with Arnold Meshkov, MD

I knew he disliked all cardiologists, but I wasn’t sure why. He was an internationally known hematologist and the Chairman of Medicine at Temple University in Philadelphia when I was a resident there in the late 1970’s. He took Morning Report just about every day and when he was not interested, he would look down at the floor and we could see his bald tan head. And he was looking at the floor one morning as one of my resident colleagues was droning on and on about the so often futile treatment of cardiogenic shock after a large anterior wall myocardial infarction.

Sol Sherry, MD, has heard too many of those case presentations over the years, about pressors, diuretics, and Swan-Ganz catheters. He was bored, but suddenly in the middle of the resident’s talk, he raised his head and said: “You know, all of your guys who are going into cardiology, acute myocardial infarction is a hematologic disease.” And then he looked down at the floor again.

Sherry had been an almost lone voice in the academic world for over twenty years by then, a proponent of the “Thrombus Hypothesis,” convinced that thrombus formation on top of an atherosclerotic plaque was the final trigger for the large anterior wall myocardial infarctions related to the “Widowmaker” lesions of the left anterior descending coronary artery. We had all seen those infarctions, with their frightening EKG patterns of ST-segment elevation known by the malignant moniker of “tombstone sign.”

The controversy about the role of thrombus in the pathogenesis of myocardial infarction had raged for decades, with strong advocates claiming that thrombus was only a secondary finding due to the primary problem of reduced flow in an atherosclerotic artery. But Sherry was also convinced of something even more important—medication could improve the outcome of a disease with close to 50% mortality at the time.

Sherry had been working with a powerful intravenous medication since the early 1950’s. He began his academic career as a hematologist working with William Tillett MD at Washington University School of Medicine in St. Louis. Dr. Tillet was the discoverer of the C-reactive protein molecule so commonly used to detect inflammation. But he and Dr. Sherry were more fascinated by a very strange molecule secreted by the streptococcus bacteria – this substance magically broke up blood clots. In honor of its humble bacterial origin, they named their molecule “streptokinase.”

Sherry and Tillett thought that streptokinase might have clinical importance. After they purified the molecule, they used it to break up the viscous pleural effusions that sometimes occurred after lung trauma and surgery. But by the late 1950’s, Sherry had a revolutionary thought – he wanted to use streptokinase in the early hours after the onset of chest pain in patients with acute myocardial infarction.

The study was a small one, but the results were astounding for the times. Overall, 87% of the 24 patients survived their infarctions! In an era before CCUs this was miraculous, and one would have expected other researchers, especially cardiologists, would have latched on to Sherry’s findings and vigorously pursued more studies.

But cardiologists focused on the new tool of the CCU, and the treatment of arrhythmias and heart failure, noble endeavors but treatment after the damage to the myocardium was already complete. They were worried about streptokinase’s allergic reaction potential, and also the risk of cerebral hemorrhage from this potent thrombolytic agent. Unable to gain the cooperation of cardiologists, Dr. Sherry began trials of streptokinase in the treatment of acute pulmonary emboli, studies that confirmed the beneficial effects of thrombolysis for hemodynamically severe pulmonary emboli, treatment that has stood the test of time.

So, streptokinase and thrombolysis lurked in the background of the treatment of myocardial infarction for almost two decades, as cardiologists tried so many different drugs to try to allow the heart to heal and have the remaining slightly damaged and normal myocardial cells compensate for the slaughter of their neighbors. But the larger point was just missed—true improvement in both short and long-term prognosis depended on restoring blood flow to the myocardium, a principle that we now accept as obvious.

Within a year of my entering my cardiology fellowship in 1979, with the memory of Sherry’s admonition resonating every time I cared for an MI patient, two startling new research studies stunned the cardiology world. A group of cardiologists in Gottenberg Germany, led by K. Peter Rentrop MD, had a great idea. They would avoid the possible toxicities of systemic intravenous streptokinase by infusing much smaller doses of the “clot-buster” medication directly into an acutely occluded coronary artery in the cardiac cath lab. In 

 of their 29 patients, the intracoronary streptokinase opened up the clot completely within minutes, and only one of the 29 people died. The results were wonderful, proving after 20 years that lysing a clot in a coronary artery early on after symptom onset saved heart muscle and improved outcomes.

In the United States, for even a few years prior, Marcus Dewood MD, a cardiologist in Spokane, Washington was accumulating data to prove the “Thrombus Hypothesis” of acute myocardial infarction. Dewood also believed that prompt restoration of blood flow was the key to improving outcomes. But he was going use surgery to achieve his goal. He convinced his surgical colleagues to perform coronary artery bypass surgery within hours of his documenting the extent of coronary artery disease by cardiac catheterization done on patients taken straight from the emergency room.

of the patients who underwent catheterization within 2 hours after their symptoms began had complete occlusion of one of their major coronary arteries. To Dewood, this abrupt cutoff of blood supply meant only one thing – he was imaging a thrombus in a coronary artery. But the bold confirmation of Dewood’s suspicion came in the operating room – the surgeons were able “fish-out” fresh thrombus using a Fogerty catheter from the artery Dewood identified in the cath lab.

The findings of Rentrop and Dewood opened the door to the era of thrombolytic therapy for acute myocardial infarction, and the dogma that “Time is muscle.” Emergency rooms around the world were placed on urgent standby for MI patients, and the results were remarkable. Many more patients survived and the complications of malignant arrhythmias and acute heart failure dropped, as long as the patients were treated promptly.

The “Thrombosis Hypothesis” confirmation led to William O’Neill, MD, and Cindy Grimes, MD, of Beaumont Hospital in Michigan to organize trials of, by the 1990’s, the well-developed technique of Andreas Grüntzig, MD, angioplasty, and use this technique instead of thrombolytic drugs for acute myocardial infarction. The “standard of care” of acute angioplasty for ST-segment myocardial infarction has been consistent for over two decades now, and the prognosis for our patients treated quickly has improved dramatically.

But it took so long for the “Thrombus Hypothesis” to gain acceptance. There will never be a good explanation for why Sherry’s study was ignored for so many years. I can understand why he didn’t like cardiologists. We always need to keep our minds open to the ideas and work of our other colleagues pushing the boundaries of the science and art of medicine.

In this column, Arnold Meshkov, MD, explores the history of the "Thrombus Hypothesis" and his experiences with thrombus in myocardial infarction as a practicing clinician. 

Arnold Meshkov, MD

Articles

Is Silence Golden? The Hunt for Hardening of the Arteries

A Picture is Worth a Thousand Words! An Anti-Vaxxer's Nightmare, with Arnold Meshkov, MD

A Hidden Hypothesis—Blood Clots and Myocardial Infarction with Arnold Meshkov, MD