The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical And Invasive Approaches) study presented at the AHA meeting this week provides further evidence that a conservative approach utilizing optimal medical therapy is an acceptable strategy for most patients with stable coronary disease (CAD).
Cardiologists have known for a decade (since the landmark COURAGE study) that outside the setting of an acute heart attack (acute coronary syndrome or ACS), coronary stents don’t save lives and that they don’t prevent heart attacks.
Current guidelines reflect this knowledge, and indicate that stents in stable patients with coronary artery disease should be placed only after a failure of “guideline-directed medical therapy.” Despite these recommendations, published in 2012, half of the thousands of stents implanted annually in the US continued to be employed in patients with either no symptoms or an inadequate trial of medical therapy.
Yes, lots of stents are placed in asymptomatic patients. And lots of patients who have stents placed outside the setting of ACS are convinced that their stents saved their lives, prevented future heart attacks and “fixed” their coronary artery disease. It is very easy to make the case to the uneducated patient that a dramatic intervention to “cure” a blocked artery is going to be more beneficial than merely giving medications that stabilize atherosclerotic plaque, dilate the coronary artery or slow the heart’s pumping action to reduce myocardial oxygen demands.
Stent procedures are costly in the US (average charge around $30,000, range $11,000 to $40,000) and there are significant risks including death, stroke and heart attack. After placement, patients must take powerful antiplatelet drugs which increase their risk of bleeding. There should be compelling reasons to place stents if we are not saving lives.
What Did ISCHEMIA Prove?
ISCHEMIA (paper unpublished but slides available here) showed that an invasive strategy (employing cardiac catheterization with resulting stenting or coronary bypass surgery (CABG)) offered no benefit over optimal medical therapy in preventing cardiovascular events in patients with moderate to severe CAD.
Rates of all-cause death were nearly superimposable over the years studied, reaching 6.5% and 6.4% at 4 years for the invasive and conservative groups,
Inclusions and exclusion criteria are listed below. Patients with unnaceptable angina despite optimal medical therapy were not included. These patients clearly benefit symptomatically from revascularization (as long as their chest pain is actually angina and not from another cause.)
All patients had stress imaging studies demonstrating moderate to severe amounts of ischemia. Such patients with very abnormal stress tests in the past have typically been sent immediately to the cath lab.
Based on ISCHEMIA we now know in these patients there is no need to do anything urgently other than institute OMT.
These patients were on good medical therapy which likely explains the very good outcomes in both conservative and invasive arms. The “high level of medical therapy optimization” is what cardiologists should be shooting for with LDL<70, on a statin with systolic blood pressure <140 mm Hg, on an antiplatelet drugg and not smoking.
Interestingly coronary CT angiography (CCTA) was utilized prior to patients receiving catheterization. I’ve been utilizing this noninvasive method for visualizing the coronary arteries increasingly prior to committing to an invasive approach.
Quality Of Life
Finally, in a separate presentation the ISCHEMIA trial showed that the invasive strategy did improve symptoms and quality of life modestly. It did not improve quality of life in those without angina symptoms.
The ORBITA study (which I wrote about here) showed that a large amount of the symptomatic improvement in patients following stenting may be a placebo effect.
Importance Of ISCHEMIA
Hopefully the results of ISCHEMIA will cut down on the number of unnecessary catheterizations, stents and bypass operations performed. This, in turn, will save our health system millions of dollars and prevent unnecessary complications.
Outside the setting of an acute heart attack the best approach to patients with blocked coronary arteries is a calm, thoughtful, and measured one which allows ample time for shared decision-making between informed patients and knowledgeable physicians. Such decisions should carefully consider the ISCHEMIA, COURAGE and ORBITA results.
N.B. Ischemia is a fantastic acronym for this study. Doctors use it a lot to describe the absence of sufficient blood flow to tissues.
N.B.2 Although I deplore the number of unnecessary caths and stents performed in the US, especially in patients without symptoms and those with noncardiac chest pain, I still utilize them in my patients with flow-limiting coronary stenoses and unacceptable anginal chest pain with symptoms despite optimal medical therapy and have noticed outstanding results. This angiogram shows a tight, eccentric LAD blockage in such a patient who now, post stent, has had complete resolution of the chest pain that limited him from even short walks.
In a previous post, the skeptical cardiologist pontificated on the causes and evaluation of the most common cause of palpitations: premature ventricular contractions or PVCs.
The vast majority of these common extra beats turn out to be benign (meaning not causing death, heart attack or stroke), and most patients with sufficient reassurance of this benignity (often accompanied by significant caffeine reduction), do well. These people usually continue to notice the beats either randomly, or with stress, but they recognize exactly what is going on and are able to say to themselves “there go my benign PVCs again,” and aren’t worried or bothered.
A small percentage of patients that I diagnose with palpitations due to benign PVCs continue to have symptoms.
Part of my initial evaluation involves checking potassium, magnesium, kidney function, and thyroid levels.
Potassium Supplementation For PVCs
Low potassium levels (hypookalemia) have been clearly associated with an increase in ventricular ectopy. Patients who take diuretics like hydrochlorothiazide (HCTZ, often used for high blood pressure) or furosemide (Lasix, often used for leg swelling or heart failure), are at high risk for hypokalemia with potassium levels less than 3.5 meQ/L.
Hypokalemia can also develop if you are vomiting, having diarrhea, or sweating excessively. There are lots of other infrequent causes including excess licorice consumption. The body regulates potassium levels closely, due to its importance in the electrical activities involved in cardiac, muscular and neurological function.
The normal range of potassium (K) is considered to be 3.5 to 5 meq/L , however, I have found that PVCs are more frequent when the potassium is less than 4.
Most of my symptomatic PVC patients with potassium less than 4 find significant improvement with potassium supplementation. I usually give them a prescription for potassium chloride (KCl) 10-20 meq daily to accomplish raising the level to >4.
An alternative to potassium supplements is ramping up how much potassium you consume in your diet. Most patients I talk to about low K immediately assume they should eat more bananas, but lots of fresh fruit and vegetables contain as much or more K than bananas.
The charts to the right show that a medium tomato contains as much K as a medium banana with a third of the calories. Avocados are a great source of K and contain lots of healthy fat. Yogurt (and I recommend full fat yogurt, of course) is a great source as well.
If you have kidney disease you are much more likely to develop hyperkalemia, or high K, and you want to avoid these high K foods. Potassium infusions are used as part of a “lethal injection” in executions because extreme hyperkalemia causes the heart to stop beating. (In fact, Arkansas is hurrying to execute 8 men between April 17 and 27 utilizing KCl. According to deathpenaltyinformation.org: “The hurried schedule appears to be an attempt to use the state’s current supply of eight doses of midazolam, which will expire at the end of April. Arkansas does not currently have a supply of potassium chloride, the killing drug specified in its execution protocol, but believes it can obtain supplies of that drug prior to the scheduled execution dates”)
Lifestyle, Stress and PVCs
It’s probably time I revealed that I have PVCs. I feel them as a sense that something has shifted inside my chest briefly, like my breath has been interrupted, like my heart has hiccoughed. If I didn’t know about PVCs and hadn’t made the diagnosis very quickly by hooking myself up to an ECG monitor in my office, I know I would have become very anxious about it.
I know exactly what causes them: stress and anxiety. And this is the case for many patients. Stress activates our sympathetic nervous system, causing the release of hormones from the adrenal gland that prepare us for “fight or flight.” These hormones stimulate the heart to beat faster and harder and often trigger PVCs.
I rarely get PVCs these days, as the major source of stress in my personal life has gone away. This is also a typical story my patient’s relate: troubling palpitations seem to melt away when they retire or change to less stressful occupations, or as they recover from depression/anxiety/grief related to death of loved ones, divorce or illness.
You can’t always control external stresses, but several factors in your lifestyle are key to managing how those stresses activate your sympathetic nervous system and trigger troubling PVCs.
Dr. Mandrola lists as Steps 5-8 (Steps 1-4 are reassurance) for PVC treatment his “four legs of the table of health”:
: good food, good exercise, good sleep and good attitude. Cutting back on caffeine and alcohol, looking critically at the dose of exercise, going to bed on time, and smiling are all great strategies for PVCs.
Of these four table legs, I consider regular aerobic exercise the most important, and modifiable factor for PVC reduction. Aerobic exercise improves mood and increases the parasympathetic (the calming component of the autonomic nervous system) activity, while lowering the output of the sympathetic nervous system.
The three factors that I find essential to handling the demanding and stressful job of being a cardiologist: restful sleep, regular, aerobic exercise and lots of love from my eternal fiancee (who also has occasional PVCs!)
Beyond sleep and exercise there is a plethora of techniques that purport to help individuals deal with stress: yoga, meditation, and progressive muscular relaxation, among them.
Apps touting methods for relaxation abound these days. My new Apple Watch is constantly advising me to engage in a breathing exercise for a minute at a time. I don’t find any of these techniques helpful for me (I haven’t found a good way to shut my brain down without falling asleep), but they may work for you.
Magnesium, Snake Oil and PVCs
Patients will find that the internet is rife with stories of how this supplement or vitamin or herb dramatically cures PVCs. You can be assured that a sales pitch accompanies these claims and that the snake oil being promoted has not been proven effective or safe. Because symptomatic PVCs like most benign, common and troubling conditions (lower back pain, fatigue, and nonspecific GI troubles come to mind), are closely related to mood and wax and wain spontaneously; the placebo effect proves powerful. In such conditions, snake oil and charlatans thrive.
Magnesium is enthusiastically hyped on the internet for all manner of cardiovascular problems including PVCs. Even Dr. Mandrola, who I respect quite a lot as an EP doc who promotes lifestyle change and who is definitely not a quack, lists his step 10 for PVCs (apologetically) as follows:
Step 10 (a): Please don’t beat me up on this one. Some patients report benefit from magnesium supplementation. I have found it helpful in my case of atrial premature beats. Let me repeat, I am not promoting supplements. Healthy patients with benign arrhythmia might try taking magnesium, especially at night. Don’t take magnesium if you have kidney disease. And if you take too much, watch out for diarrhea.
Most of the internet’s top quacks, however, greedily market and glowingly swear by magnesium. A Google search for magnesium cardiovascular disease yields 833,000 entries and the first page is a Who’s Who of quackery, including Dr Mercola (strong candidate for America’s greatest quack), Dr. Sinatra (see here, currently in the semifinals for America’s greatest quack cardiologist), NaturalNews and Life Extension (see here). This totally unsupported and dangerous blather from the Weston Price Foundation is often repeated and is typical:
(magnesium) Deficiency is related to atherosclerosis, hypertension, strokes and heart attacks. Deficiency symptoms include insomnia, muscle cramps, kidney stones, osteoporosis, fear, anxiety, and confusion. Low magnesium levels are found in more than 25 percent of people with diabetes. But magnesium shines brightest in cardiovascular health. It alone can fulfill the role of many common cardiac medications: magnesium inhibits blood clots (like aspirin), thins the blood (like Coumadin), blocks calcium uptake (like calcium channel-blocking durgs such as Procardia) and relaxes blood vessels (like ACE inhibitors such as Vasotec) (Pelton, 2001).
Magnesium levels are very important to monitor in hospitalized and critically ill patients, especially those receiving diuretics and medications that can effect cardiac electrical activity.
However, for individuals with normal diets and palpitations due to PVCs, there is scant evidence that it plays a significant role in cardiovascular health.
The MAGICA study looked at supplementation with both magnesium and potassium (in the active treatment group, daily oral dosing consisted of 2 mg of magnesium-dl-hydrogenaspartate (6 mmol magnesium) and 2 mg of potassium-dl-hydrogenaspartate (12 mmol potassium) daily. The dose was chosen to increase the recommended minimal daily dietary intake of magnesium (12 to 15 mmol) and potassium (20 to 30 mmol) by ∼50% in addition to usual diet ) in 307 patients with more than 720 PVCs per hour and normal baseline K and Mg levels.
The patients receiving magnesium/potassium supplements showed a decrease of 17% in frequency of PVCs but no improvement in symptoms.
A 2012 study in a Brazilian journal evaluated magnesium pidolate (MgP) in 60 patients with both PVCs and premature atrial contractions (PACs). The dose of MgP was 3.0 g/day for 30 days, equivalent to 260 mg of Mg elemental.
93% of patients receiving MgP experienced improved symptoms compared to only 13% of patients recieiving placebo. Both PVC and PAC frequency was reduced in those receiving MGP, whereas they increased by 50% in those receiving placebo.
This small study has never been reproduced, and the main results table makes little sense. It would not have been published in a reputable American cardiology journal and cannot be relied on to support magnesium for most patients with benign PVCs or PACs.
Drug or Ablation Treatment of PVCs: Usually Not Needed
A small percentage of my patients require treatment with beta-blockers which reduces the effects of the sympathetic nervous system on the heart. Very rarely, I will use anti-arrhythmic drugs. And every once in a while, very frequent PVCs resulting in cardiomyopathy require an ablation.
However, the vast majority of patients with benign PVCs, in my experience, feel drastically better with a simple non-pharmacological approach consisting of 4 factors:
Reassurance that the PVCS are benign
Caffeine (or other stimulant) reduction
Lifestyle adjustment with regular aerobic exercise
The skeptical cardiologist was in Atlanta recently visiting his Life Coach (LCOSC). Oddly enough, the wife of the LCOSC (who I’ll call Lisa) had just undergone a coronary calcium scan and it came back with a high score. Most women her age (58 years old) have a zero score but hers came back at 208 .
What is the significance of a calcium score of 208 in this case?
The CT scan for calcium (discussed by me in more detail here) focuses entirely on quantifying the intense and very specific kind of x-ray absorption from calcium. The three-dimensional resolution of the scan is such that the coronary arteries which supply blood to the heart can be accurately located and the amount of calcium in them very accurately and reproducibly added up. Calcium is not in the arteries normally and only accumulates as atherosclerotic plaque builds up over time. The build up of fatty plaque (atherosclerosis) is the major cause of coronary artery disease (CAD, sometimes termed coronary heart disease (CHD)) which is what causes most heart attacks and most death in both men and women in the U.S.
We can enter Lisa’s numbers into the online MESA calculator to see how she compares to other white 59 year old women. The calculator tells us that 72% of her peers have a zero calcium score and a score of 208 is higher than 95% of her peers. Although the 95th percentile is a good place to be for SAT scores it is not for atherosclerosis. This means substantial amount of fatty atherosclerotic plaque has built up in the arteries and puts the individual at significantly greater risk for heart attack and stroke. A calcium score of 100-300 confers a 7.7 times increased risk compared to an individual with similar risk factors with a zero calcium score.
Most of the risk factors that we can measure to assess one’s risk of heart attack (blood pressure, diabetes, smoking) were absent in Lisa. Her cholesterol levels had risen in the last 10 years but when I entered her numbers (total cholesterol 221, HDL 68) into the ASCVD risk estimator her 10 year risk came back at 2.5%. This is considered low and no treatment of cholesterol would be advised by the new guidelines.
The only clue that her cardiologist would have that Lisa has advanced premature atherosclerosis is that her mother had coronary heart disease at an early age, something we call premature CAD. Her mom at the age of 62 suffered a heart attack and had a stent placed in one of her coronary arteries. The occurrence of significant premature CAD in a parent or sibling substantially increases the chances that a patient will have premature CAD and the earlier it occurred in the parent or sibling the higher the risk.
Some of this excess risk is transmitted by measurable risk factors such as hypertension and hyperlipidemia and some through lifestyle factors but the majority of it is through genetic factors that we haven’t fully identified.
How much of an individual’s risk for heart attack is determined by genetics versus lifestyle?
A large Swedish study found that adopted men and women with at least one biological parent with CHD were 1.5 times more likely to have CHD than adoptees without. In contrast, men and women with one adoptive parent were not at increased risk.
Since 2007 an intense project to identify genetic factors responsible for CAD has been underway at multiple academic centers. Thus far 50 genetic risk variants have been identified. According to Dr. Robert Roberts
” All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis”
How well do the standard risk factors capture the individuals risk for heart attack?
The standard approach to estimating risk fails in about 25% of individuals as it does not accurately convey the high risk of the patient with family history and it overestimates risk in many elderly individuals who have an excellent family history.
It is in these patients that testing for the actual presence of atherosclerosis, either by vascular screening or coronary calcium is helpful.
Reducing The Excess Risk of Premature CAD
For many individuals there are clear-cut lifestyle changes that can be implemented once advanced CAD is identified: cigarette smoking cessation, weight loss through combinations of diet and exercise with resulting control of diabetes, However, many patients like Lisa, are non-smokers, living a good lifestyle, eating an excellent diet with plenty of fresh fruit, vegetables, fish and healthy oils and without obesity or diabetes. There is no evidence that modifying lifestyle in this group is going to slow down an already advanced progression of atherosclerosis.
Patients like Lisa have inherited predisposition to CAD, it is not due to their lifestyle.
Lisa’s cardiologist suggested she get a copy of Dr. Esselstyn’s book “Prevent and Reverse Heart Disease”. This book, based on the author’s experience in treating 18 patients with advanced CAD espouses an ultra low fat diet. The author declares that “you may not eat anything with a face or a mother (meat/poultry/fish)” and bans full fat dairy products and all oil (“not even a drop”)
Such “plant-based diets” (codeword for vegan or vegetarianism) lack good scientific studies supporting efficacy and are extremely hard to maintain long term. There is nothing to suggest that Lisa’s long term risk of heart attack and stroke would be modified by following such a Spartan dietary regimen.
Her cardiologist did recommend two things proven to be beneficial in patients with documented advanced CAD: statins and aspirin.
Taking a statin drug will arrest the atherosclerotic process and reduce risk of heart attack and stroke by around 30% as I’ve discussed here and here.
An aspirin is now indicated since significant atherosclerosis has now been documented to be present as I’ve discussed here.
We can blame a lot of heart disease on lifestyle: poor diets and lack of exercise are huge factors leading to obesity, diabetes, hypertension and hyperlipidemia, but in many patients I see who develop heart disease at an early age, lifestyle is not the issue, it is the genetic cards that they have been dealt.
Until we develop reliable genetic methods for identifying those at high risk it makes sense to utilize methods such as vascular screening or coronary calcium to look for atherosclerosis in individuals with a family history of premature CAD.
Once advanced atherosclerosis is identified, we have extremely safe and effective medications that can help individuals like Lisa deal with the cardiovascular cards they have been dealt.