Your Angiogram Was Clean. Nobody Tested Whether Your Artery Clamps.

For those that have been following along, last week was the story: two years of chest pressure after my stent, two cardiologists ready to call it anxiety, a third who kept looking, and a cath-lab test that finally showed my right coronary artery clamping down on its own, a coronary artery spasm, with no plaque to blame. This week is the science I promised, and the test that found my problem is one most people never get.

Nearly 400,000 people with no known coronary disease had an elective heart catheterization in the American College of Cardiology's national registry, and slightly more than one third of them had an obstructive blockage. About 39 percent had arteries that looked essentially clean, under 20 percent narrowing in every vessel.¹ I have had that kind of clean result twice now, a CT angiogram earlier this year and the cath table on August 26, both after a stent in 2025, with the same chest pressure the whole time.

The catheterization is the most invasive test cardiology has. A doctor threads a tube up an artery in your wrist to your heart, injects dye, and takes X-ray pictures of the coronary arteries as the dye flows through. It answers one question very well: is there a clog. It does not answer the second question, which is what the artery does when nobody is provoking a specific type of stress to it. An artery is a dynamic muscular tube, not a static pipe. A pipe fails by clogging. A muscular tube can also fail by clamping down when there is no real physiological need. And this clamp does not show on regular CT or MRI scans. And it doesn't even show in a good standard invasive angiogram unless specifically provoked.¹⁰

This post is about what a cath lab can do when someone asks it whether the problem has to do with the muscular layer of the artery wall versus an obvious problem from atherosclerosis that can be visually seen. That is not the cath lab failing. It was built to find and open blockages, because a blockage is what kills fastest. Most of the time nobody does.⁶

The Bottom Line

Most elective catheterizations for suspected coronary disease find no obstructive blockage.¹ Among people sent for the test because of stable angina, that was true for 65 percent of women and 32 percent of men in a Danish cohort of more than 11,000 patients referred for it.² When the clean-artery patients are then tested for how their arteries function rather than how they look, most have a real disorder: in the Scottish cohort that did this systematically, 52 percent had isolated microvascular angina, 17 percent isolated vasospastic angina, 20 percent both, and 11 percent non-cardiac chest pain.³ The authors' phrase was "over three quarters." Add the three disorder categories, everything except the 11 percent non-cardiac, and it is 89 percent, roughly nine in ten.

Spasm is a spectrum, and the version most of us were taught is the minority. Prinzmetal's angina, one spot on an artery clamping shut with ST elevation on the ECG, is a focal spasm. Among patients whose acetylcholine test provoked spasm in a large artery, the kind an angiogram can see, at a German and a Japanese center, focal spasm was 15 percent and diffuse spasm 85 percent.⁴ The common form narrows the whole vessel along its length and, I think, is easier to miss. In the Stuttgart cohort, more than half of the provoked spasm, 55 percent, was in vessels too small to see on an angiogram.⁵

The test that makes the diagnosis is rarely run in the U.S. or Europe,⁶ and the two drugs a cardiologist reaches for first when spasm is suspected, a calcium-channel blocker and a nitrate, can blunt it.⁷¹⁵¹⁶ It is not benign either; the European guideline ties it to sudden cardiac death, heart attack, and fainting.⁸ In a meta-analysis that pooled 54 studies of ischemia with no blocked arteries, the vasospastic-angina group ran 0.7 deaths or heart attacks and 1.1 major adverse cardiovascular events per 100 patient-years. The authors call the overall rate low. I call a rate that is measured and not zero real.⁹ Beta blockers, in the Japanese guideline's words, "can induce coronary spasm."⁷ I was on one for two years.

What I actually want to know is what share of the chest pain filed under "anxiety" is spasm. As far as I can find, nobody has measured it, because you would have to run the provocation test on people who were sent home with an anxiety label, and those are exactly the people nobody sends back to the cath lab. For two years I was one of them.

Vocabulary that matters

• Angiogram versus function test. The angiogram is the dye picture; it shows the shape of the artery. A function test measures what the artery does: how much it can open, how much the small vessels resist flow, and whether it clamps when provoked.
• Coronary vasospasm. The muscle in the wall of a heart artery contracts on its own and narrows or closes the artery for a while. Also called coronary artery spasm or vasospastic angina.
• Microvascular angina. Chest pain from the small vessels an angiogram cannot see, either because they cannot open enough or because they spasm. I have written about those small vessels before.
• Provocation test. Acetylcholine, a chemical the body uses to signal blood vessels, is injected into the artery in rising doses to see whether it clamps, reproduces your pain, and changes your ECG.
• CFR, IMR, FFR. Three numbers from a pressure wire in the artery. Coronary flow reserve: how many times over blood flow can increase on demand. Index of microcirculatory resistance: how hard the small vessels push back. Fractional flow reserve: whether a narrowing actually limits flow.
• INOCA or ANOCA. Ischemia, or angina, with no obstructive coronary arteries. The formal name for chest pain with normal coronaries: the pain and the clean pictures together.

How vasospastic angina is diagnosed: what a cath does when it is not placing a stent

The emergency system I work in is not doing anything wrong when it sends a chest-pain patient to the cath lab that gives a green light when the pictures are clean.

The lab was built to find and open blockages, because a blockage is the thing that kills fastest, and escalating from an ECG to a stress test to an angiogram in that order is the design. Every test I got was the right test for the question it was built to answer, and each one answered it. The typical test tells you whether the artery is clogged. It does not tell you whether the artery is dysfunctional and is clamping down when it shouldn't.

On August 26, according to my procedure log, a sheath went into the artery at my right wrist, dye pictures were taken of both coronary systems, and a pressure wire was threaded into the left anterior descending artery, the one that runs down the front of the heart. An adenosine infusion opened the small vessels as far as they would go, and the wire produced three numbers: fractional flow reserve 0.90, coronary flow reserve 8.5, index of microcirculatory resistance 13. All three normal. My small vessels can open, and they do not push back.

Then acetylcholine (the stressor), in three rising doses through the catheter. Mild diffuse narrowing on the pictures. The chest and throat pressure I had been describing for two years, first at a two out of ten, then a four, reproduced on the table. A transient T-wave inversion on the ECG, an electrical sign of heart muscle short on blood. Then 200 micrograms of nitroglycerin into the artery, and the right coronary artery, which had read 30 to 50 percent narrowed on the first dye injection before any acetylcholine was given, read normal. A fixed plaque does not disappear with nitroglycerin. Dysfunctional muscle narrowing does. Final diagnosis, line one: moderate spontaneous coronary artery spasm. Line three: mild epicardial coronary endothelial dysfunction, the inner lining of the large arteries not doing its job of telling the muscle to relax. You are kept awake for the provocation on purpose. You know what the drug is supposed to do to you, and then it does it. I have run codes on people whose ECGs looked like mine did on that monitor.

Does coronary artery spasm show on an ECG?

Only while the artery is clamped. Between episodes the resting ECG reads normal, which is why the European guideline asks for a 12-lead ECG recorded during the pain, and, when episodes are frequent, a wearable monitor that watches the ST segment until one is caught.⁸ The signature it is looking for is a transient ischemic change that comes with the pain and leaves with it.¹⁷

From the emergency department, you do not get to the cath lab by describing your symptoms well. You earn the table with a troponin that is rising, or an ECG that is changing in front of us, or both. Those are the right gates for a heart attack, because a heart attack is what the cath lab exists to stop. Spasm gives you neither unless it is squeezing at the moment the ECG is running, and it usually is not. So a spasm patient walks in with a normal troponin and a normal ECG and, correctly by the chest-pain protocol, usually walks back out.

I have been an ER nurse for years, and until my own cath I did not know there were types of coronary spasm other than the textbook Prinzmetal's, or that the common kind could cause exactly the symptoms I had. Most of the physician friends I described it to did not know the extent of it either. It is not something the ER is built to find.

In a report of 17,700 patients who had a provocation test, summarized in the Japanese guideline, serious complications occurred in 0.89 percent, with one death.⁷ That is a real risk, and I weighed it. It is not, in my read, why the test is rarely run.

How common this is, measured

In the American College of Cardiology's national registry, nearly 400,000 patients without known coronary disease had an elective catheterization between 2004 and 2008. Obstructive disease was found in 37.6 percent; essentially no disease at all, under 20 percent narrowing in every vessel, in 39.2 percent.¹ These were people a cardiologist had already decided needed the test, and by my subtraction roughly six in ten came off the most definitive test in cardiology with no obstructive blockage found.

At two centers in the west of Scotland, 391 patients with angina were enrolled at the time of their angiogram; 185, or 47 percent, had no obstructive disease, and 151 of those went straight on to function testing in the same session, the same three wire measurements I had plus acetylcholine.¹⁰ Fifty-two percent had isolated microvascular angina, 17 percent isolated vasospastic angina, 20 percent both, and 11 percent non-cardiac chest pain.³ The authors wrote "over three quarters." The three disorder categories add to 89 percent, and I will say roughly nine in ten, with the caveat that these were angina patients already selected for angiography; my read is that the figure is an upper end for clean-artery angina patients, not a rate for everyone with chest pain. A second center, in Stuttgart, had already found the same pattern with acetylcholine alone: 62 percent of 124 clean-artery angina patients had provokable spasm, 55 percent of it in the small vessels.⁵

The Glasgow group randomized those 151 patients to either get the function-test result with their medication matched to it, or a sham procedure and usual care. At six months the tested-and-treated group's angina score had improved by 11.7 points more on the Seattle Angina Questionnaire, with no difference in cardiac events over that window.¹⁰ A second randomized trial, run in the Netherlands and published in 2025, found the same thing: 153 angina patients with no blockage, all tested at their angiogram, and disclosing the result with treatment matched to it improved the same angina score by 9.4 points at six months, with no major adverse cardiac events in either group in that window.²⁸ That is the same test I had, and in two randomized trials, running it and matching treatment to the result improved angina in people whose angiograms showed no blockage.

An expert working group convened by the American College of Cardiology reported that two US registry databases suggest at least three to four million women and men have signs or symptoms suggestive of ischemia with no obstructive coronary disease.¹¹ That is a database-derived estimate restated from two earlier papers, not a count; nobody counted these patients, and it does not separate spasm from microvascular disease. Treat it as the experts' floor.

What happens to the clean-artery patient

Reassured is the word the cardiologist uses, and I have heard it before. In my case the word was anxiety, and it came from two good doctors looking at a clean CT angiogram, a normal echo, and a home ECG that never caught anything, and reaching for the only explanation the pictures left them. I reached for it too. I was on propranolol by then, chosen partly because it takes the edge off the physical side of anxiety, and it was quietly making the real problem worse the whole time. The data on symptomatic patients with clean angiograms say something else.

In the Women's Ischemia Syndrome Evaluation, symptomatic women whose angiograms showed completely normal arteries had a five-year cardiovascular event rate of 7.9 percent, against 2.4 percent in age- and race-matched asymptomatic women from a separate community cohort, after adjusting for risk factors.¹² The authors' own summary: a normal-looking artery in a woman with symptoms carried approximately three times the event rate of a woman with no symptoms at all.

The Danish group invited 357 of their patients to a questionnaire two to three years after a first angiogram for suspected stable angina, and 83 percent responded. Persistent angina was present in 49 percent of those with completely normal arteries, versus 41 percent of those who had an actual blockage, who presumably got it fixed. Among the patients still hurting, 42 percent scored in the anxiety range on a screening questionnaire versus 21 percent of those no longer having angina at least monthly.¹³ Those are screening scores, not diagnoses, and the study cannot say whether the persistent pain drives the anxiety or the other way around. The authors' own conclusion is the one I would put on the wall of every cath lab: "Contrary to common perception, excluding obstructive CAD in stable angina does not ensure a favorable disease course."¹³ In the same group's registry of 11,223 stable-angina patients followed for a median of 7.8 years, those whose arteries looked normal on the angiogram were hospitalized for cardiovascular disease three times as often as 5,695 symptom-free comparators.¹⁴

So the clean-artery pool is large, most of it has a real disorder when someone tests function, and the people in it keep hurting and keep getting admitted. What nobody has measured, as far as I can find, is how many of them were told it was anxiety and never got the test. For two years I was in that pool with an anxiety label and no function test. Anxiety is a real diagnosis, and for some people in that pool it is the whole answer. The point is that nobody checked.

My read: a clean angiogram without a function study has ruled out a blockage and nothing else. That is the point where anxiety went into my chart.

Why it gets missed, and why treating first makes it harder to find

The first reason is that the test is rarely run. That is the Stuttgart group's characterization, written in 2016 by a center that runs the test as daily routine. Intracoronary acetylcholine testing was introduced more than thirty years ago and is "only rarely applied in the U.S. or Europe."⁶ I could not find a count of how often a clean angiogram is followed by a function study in an American cath lab. My guess is a small number, and that is a guess.

The second reason nearly caught me. If spasm is suspected, the reasonable thing for a cardiologist to do is start a calcium-channel blocker, the drug that stops spasm, or a nitrate. Both can blunt the provocation test. In a Japanese cath series, patients who had stopped amlodipine, an ultra-long-acting calcium-channel blocker, two days before the test, the recommended washout, still had roughly a third the odds of a positive result.¹⁵ In a 2025 study, 40 patients with proven spasm were re-tested after nitroglycerin had been given in the lab, and the same large-artery spasm came back in only 55 percent.¹⁶ The Japanese guideline says calcium antagonists and long-acting nitrates "should be discontinued for at least 2 days before testing if possible," and the European guideline's testing protocol specifies at least 24 hours of washout from both.⁷⁸ That washout is the cardiologist's call before a scheduled test, not something to do on your own.

What follows is my inference, not a study's finding. Nobody has studied the sequence a patient lives through: chest pain, clean pictures, a calcium-channel blocker started on suspicion, partial relief, and months later a provocation test, on the drug or barely off it, that reads negative and ends the workup. Mechanistically, that sequence can produce a false negative. I think it happens, and I think it is one of the reasons the anxiety chart entry is so durable.

The spectrum: what spasm is

Vasospastic angina has an international definition. The Coronary Vasomotion Disorders International Study Group, COVADIS, an international panel of cardiologists, built it from three criteria: chest pain that responds to nitrates, a transient ischemic change on the ECG during an episode, and documented spasm on the angiogram.¹⁷ The Japanese guideline puts a number on the last one. A positive provocation test is a transient occlusion of more than 90 percent at one spot, or a 90 percent diffuse narrowing across two or more adjoining segments, with the pain and the ECG change to go with it.⁷ The same group later gave microvascular angina its own definition: symptoms and objective evidence of ischemia, no obstructive disease, and a reduced coronary flow reserve, spasm provoked in the small vessels, or both.¹⁸ One international group wrote both definitions so that studies and registries would share a common language, and both disorders now sit in the Japanese and the European guidelines.⁷⁸ This is a formally defined diagnosis, not a fringe label.

Inside those definitions, the version in the textbook is the minority pattern. Among patients whose acetylcholine test provoked spasm in a large artery at the German and Japanese centers, focal spasm, one spot clamping, was 15 percent; diffuse spasm, the whole vessel tightening along its length, was 85 percent.⁴ Every patient in that series had a narrowing of at least 90 percent on the test, so diffuse does not mean mild; it means spread along the vessel. I was taught Prinzmetal's in school, a diagnosis you could see from across the room. Mine was the common kind, diffuse and quiet, and I had never been taught it existed. In my case the large-artery spasm was the diagnosis and the small-vessel numbers were normal. That is one pattern of several; another patient's test can show small-vessel spasm with normal large arteries, with the same pain and the same ECG change.

Real patients, not mine. Figure reproduced from Suzuki S et al., Cardiovascular Intervention and Therapeutics 2021, PMID: 33108592, corrected Figure 3 (correction at PMID: 33398770), doi:10.1007/s12928-020-00720-z, CC BY 4.0. Top row is a focal spasm, bottom row a diffuse one; each shows baseline, the acetylcholine response, and the reopening after a nitrate.

Not benign, and not only women

Last week's post covered what the diagnosis meant for me. Here is the registry view. Vasospastic angina is, in the European guideline's words, "associated with major adverse events, including sudden cardiac death, acute MI, and syncope."⁸ In an international registry of 1,457 spasm patients, the five-year event-free survival estimate was 76.6 percent among the Caucasian patients, against 86.7 percent among the Japanese patients.¹⁹ Roughly one in four Caucasian patients in that registry had a major adverse cardiac event within five years, by my arithmetic on their survival figure; in the full paper that composite includes hospital admissions for unstable angina and heart failure, not only heart attacks and deaths. That arm was 51 percent male while the Japanese arm was 68 percent male.¹⁹ The clean-artery cohorts skew female, 68 percent in the Scottish study,³ and the German and Japanese spasm series was 54 percent female,⁴ so the spasm registries sit closer to even than the "women's problem" label suggests. If you are a man who has been told this is a women's problem, or a woman told it is rare, the registries say otherwise.

What causes coronary artery spasm, and where aging enters

The wall of a coronary artery is muscle, and that muscle contracts or relaxes depending on the chemical signals it receives. The inner lining, a single sheet of cells called the endothelium, releases nitric oxide, a gas that tells the muscle underneath it to relax. The muscle layer itself does the squeezing, and an enzyme in it called Rho-kinase works like a switch: when it is on, it blocks the enzyme that lets the muscle relax again, so the muscle stays contracted. In spasm, Rho-kinase is over-active.²¹

That is Hiroaki Shimokawa's position, stated in his 2014 European Heart Journal lecture: the central mechanism of coronary spasm is hypercontraction of the vascular smooth muscle cells, "not endothelial dysfunction."²¹ That is a synthesis, not a measurement. The measurement is a small human study from Kyushu, with Shimokawa as a co-author: 20 patients with vasospastic angina had spasm provoked with acetylcholine, then were re-challenged after either saline or fasudil, a drug that blocks Rho-kinase. Fasudil markedly attenuated the provoked constriction, and in all 15 treated patients the chest pain and ischemic ECG changes did not occur.²² Fifteen treated people, five controls, no randomization described, one center. Block Rho-kinase in those fifteen coronary arteries and the provoked spasm did not happen.

The lining's role is real and, in Shimokawa's synthesis, secondary. In 1986, 18 people were studied in a cath lab: four with normal arteries, eight with advanced narrowing, and six with mild disease. Acetylcholine dilated the four normal coronary arteries and constricted all eight with advanced narrowing and five of the six mildly diseased ones. Every vessel still opened to nitroglycerin, which relaxes the muscle directly and does not need the lining.²³ That was a study of atherosclerosis, not of spasm patients, so the paper shows what its authors read as a failing lining; it does not show that the lining causes spasm. The third line of my own cath report, mild epicardial coronary endothelial dysfunction, is that signature: my lining did not relax the artery the way it should have when the test asked it to, and my muscle contracts harder than it should. The muscle side is the one the calcium-channel blocker treats.

This is where aging biology comes in, and only some of it is measured in spasm patients.

Measured, in spasm patients: the outside of the artery is inflamed. In a Tohoku imaging study, 27 patients with acetylcholine-proven diffuse spasm of the left anterior descending artery were compared with 13 people with suspected angina and no spasm. The fat around the coronary artery was larger, the tissue around the artery took up more glucose tracer on PET, a scan that lights up inflamed tissue, and Rho-kinase activity in circulating white blood cells was higher; under medical treatment, the PET signal and the Rho-kinase activity both fell.²⁴ Forty people, one center, and the Rho-kinase was measured in blood cells as a proxy. Still, this is the direct human link between coronary spasm and inflammation of the outer vessel wall, and it is why the hallmark of aging I would put first here is chronic inflammation.

Measured in tissue and cells, not in spasm patients: senescent cells live in the lining of atherosclerotic coronary arteries. Senescence is the state a cell enters when it stops dividing and starts secreting inflammatory signals instead, and it accumulates with age; I have written about those cells before. In coronary arteries from people who had ischemic heart disease, a senescence marker stained strongly in the atherosclerotic lesions, and the marked cells were endothelial; human aortic endothelial cells pushed into senescence in a dish had less eNOS activity, and eNOS is the enzyme that produces nitric oxide.²⁵ That is autopsy tissue and cultured cells, and the disease studied was atherosclerosis. I could not find a study that has looked for senescent cells in the arteries of spasm patients, so cellular senescence, the second hallmark I would name, sits here as an inference.

Measured in aging humans, and it complicates the simple story: in 56 healthy men aged 18 to 78, the older men's arteries opened less to acetylcholine, used here as a dilation probe rather than a spasm test, but their lining cells did not make less eNOS. What was higher was endothelin-1, a major constrictor signal the lining makes.²⁶ Those were arm arteries in healthy men, not coronaries in spasm patients. I include this paper because the easy version, that an aging artery just loses its nitric-oxide machinery, is not what the human data show. The shift is toward more constrictor signal.

I could not find anyone who has measured senescence in a spasm patient's artery, and it is the study I would most want to see run next.

My read: the mechanism is shown in humans, in a provocation study, at the level of Rho-kinase and the drug that blocks it; the lining's role is measured but secondary; the inflammation is measured in spasm patients; and the tie to aging is an inference from the hallmarks framework,²⁷ not a finding.

What I changed

Diltiazem. Mayo started me on diltiazem ER 120 mg on August 28, the calcium-channel blocker that is first-line for this, at the starting dose. Nebivolol stayed for now, with a plan to watch blood pressure, heart rate, and the ECG rather than pull it the same week as everything else changed. I turned down a daily long-acting nitrate. That is a personal call, not advice: the body adapts to a nitrate that is always there, and I would rather keep nitroglycerin as the thing that works when I need it.

The number I own now is a baseline: coronary flow reserve 8.5, microcirculatory resistance 13, fractional flow reserve 0.90. All normal, all measured, all in my chart for the next time someone wants to know whether something changed.

I was angry for about a day, honestly. Two years of being told a thing about my own body that was not true, by people I work with and trust, because the test that would have settled it is one nobody orders. Then the anger turned into what it turned into after the stent: a plan, and this newsletter.

The Calibrated Claim Audit

Claim	Evidence	My read
A normal angiogram rules out a cardiac cause	400k-patient registry; function-testing cohorts 135	No. It rules out a blockage.
Coronary spasm is the rare Prinzmetal's kind	85% diffuse, 15% focal, two centers 4	The textbook form is the minority.
Function testing follows a clean cath as routine	Expert characterization; no measured rate found 6	Rare, by the people who run it.
Starting a CCB before testing costs the diagnosis nothing	Observational data; two guidelines 151678	It can blunt the only test that names it.
Beta blockers are safe first-line for unexplained chest pain	1982 trial; Japanese guideline 207	Not if it is spasm.

Commercial distortion risk: low to moderate. The money in this topic is in the devices, the pressure wires and testing kits, rather than in a product. One cited study (Rehan 2025) was funded by a government research scholarship, but three of its eight authors disclose honoraria or research support from device companies; authors of the outcomes meta-analysis disclose ties to Abbott Vascular and Boston Scientific; and three of the five authors of the hallmarks-of-aging framework paper declare commercial interests in the aging field, two in senescence or aging therapeutics and one in commercial telomere testing. None of that makes a claim wrong, but it changes how carefully I read the evidence. The senescence tie above is an inference for a different reason: nobody has measured it in spasm patients.

On the last row, the beta blocker, because I took one for two years: a 1982 double-blind trial found that propranolol given as sole therapy significantly prolonged the duration of angina attacks without significantly changing their frequency.²⁰ The European guideline gives calcium-channel blockers Class I, Level A for isolated vasospastic angina, and the Japanese guideline lists among its diagnostic reference items that attacks are suppressed by calcium-channel blockers but not by beta blockers.⁸⁷ None of that is a recommendation for you. It is what these drugs do to a spasming artery: a calcium-channel blocker suppresses the attacks, a beta blocker does not, and in that trial propranolol made them last longer. If you have unexplained chest pain and you are on a beta blocker, that is a question to bring to your cardiologist.

The Final Signal

• What the "clean angiogram means you're fine" claim gets right: it rules out a blockage, which is what kills fastest, and the cath lab was built to do exactly that.
• What it gets wrong: an angiogram cannot show a spasm unless one happens during the injection.¹⁰ Most clean-artery angina patients have a real disorder when someone tests function.³⁵ The test is rarely run in the U.S. or Europe,⁶ and the first-line drugs can blunt it.¹⁵¹⁶
• What I changed: Diltiazem started, nebivolol watched, no daily nitrate by choice, and a set of flow numbers in my chart that mean the next test has something to be compared to.
• What would change my mind: a study that takes anxiety-labeled chest pain, runs provocation testing, and finds spasm rare. As far as I can find, nobody has run it.
• What's next: fibrous caps, and what keeps a plaque from rupturing.

More on the tests that find what pictures miss: the Diagnostic Toolkit series, and the Patient Advocacy posts on how to ask for them.

If your chest pressure is real, your tests keep coming back normal, and the word anxiety has started showing up in the room, ask one question: has anyone tested how my arteries function, or only how they look? A clean angiogram rules out a blockage. It does not rule out a spasm. There is a test for the spasm, it exists in cath labs right now, and most people who need it never hear that it does. If your cardiologist does not do this testing, ask for a referral to a center that does; the European guideline now recommends the test for people whose symptoms persist on treatment and whose quality of life is poor.⁸ You may have to argue for it. I did, and I am an ER nurse who works down the hall from the lab. Your health is truly in your hands, and nobody is going to fight for that test as hard as you will.

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References

1. Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886-895. PMID: 20220183 [Finding: Among nearly 400,000 US patients with no known coronary disease who had an elective catheterization, only 37.6 percent had an obstructive blockage and 39.2 percent had essentially clean arteries, under 20 percent narrowing in every vessel. The study measured anatomy only and says nothing about how many clean-artery patients had spasm.]
2. Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. PMID: 21911339 [Finding: In 11,223 Danish patients referred for an angiogram for stable angina, 65 percent of women and 32 percent of men had no obstructive disease, and those patients still carried a higher risk of major adverse cardiovascular events than a reference population without ischemic heart disease. Anatomic definition, no function testing.]
3. Ford TJ, Yii E, Sidik N, et al. Ischemia and no obstructive coronary artery disease: prevalence and correlates of coronary vasomotion disorders. Circ Cardiovasc Interv. 2019;12:e008126. PMID: 31833416 [Finding: Of 391 UK angina patients, 185 had no obstructive disease; among the 151 who then had invasive function testing, 52 percent had isolated microvascular angina, 17 percent isolated vasospastic angina, 20 percent both, and 11 percent non-cardiac chest pain. Angina patients enrolled at two centers, not a population sample; my read is that the figure is a ceiling for that kind of patient.]
4. Suda A, Seitz A, Odaka Y, et al. Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm-more similarities than differences? Heart Vessels. 2021;36:337-344. PMID: 33044621 [Finding: Across a German and a Japanese center, among 149 patients with resting angina, unobstructed arteries, and acetylcholine-provoked spasm of a large (epicardial) artery, diffuse spasm was the pattern in 85 percent and focal spasm in 15 percent, with no significant difference between countries; the full text defines a positive test as a diameter reduction of at least 90 percent. It classifies spasm by its shape on the angiogram; its abstract reports no ECG breakdown by spasm type.]
5. Ong P, Athanasiadis A, Borgulya G, et al. High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study. J Am Coll Cardiol. 2012;59:655-662. PMID: 22322081 [Finding: Of 124 stable-angina patients with unobstructed arteries who had acetylcholine testing, 62 percent had provokable spasm; of those, 45 percent in the large arteries and 55 percent in the small vessels. A Stuttgart, Germany cohort of consecutive patients already referred for angiography; no outcome data.]
6. Ong P, Athanasiadis A, Sechtem U. Intracoronary acetylcholine provocation testing for assessment of coronary vasomotor disorders. J Vis Exp. 2016;(114):54295. PMID: 27583694 [Finding: A methods paper from the Stuttgart group, which runs the test as daily routine, stating that acetylcholine testing was introduced more than 30 years ago and is "only rarely applied in the U.S. or Europe." An expert characterization with no measured rate behind it.]
7. Hokimoto S, Kaikita K, Yasuda S, et al. JCS/CVIT/JCC 2023 guideline focused update on diagnosis and treatment of vasospastic angina (coronary spastic angina) and coronary microvascular dysfunction. Circ J. 2023;87:879-936. PMID: 36908169 [Finding: The dedicated Japanese guideline: calcium-channel blockers' efficacy "well established," about 20 percent of patients refractory, beta blockers noted as able to induce or exacerbate spasm, provocation testing recommended for patients suspected on symptoms and not diagnosed noninvasively (Class I, Level B), a positive test defined as a transient total or sub-total occlusion of more than 90 percent or a 90 percent diffuse narrowing in two or more adjoining segments with ischemic signs or symptoms, calcium antagonists and long-acting nitrates to be stopped at least two days before testing "if possible," and serious complications in 0.89 percent of 17,700 patients undergoing provocation testing, a figure the guideline summarizes from Sueda and Kohno 2016. Quotes are page-cited from the full text; the record has no abstract.]
8. Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45:3415-3537. PMID: 39210710 [Finding: The European guideline gives calcium-channel blockers a Class I, Level A recommendation for isolated vasospastic angina, nitrates Class IIa, Level B, recommends a 12-lead ECG during angina and ambulatory ST-segment monitoring when symptoms are frequent, recommends invasive coronary functional testing (Class I, Level B) for persistently symptomatic patients with suspected ANOCA/INOCA and poor quality of life despite medical treatment, and its testing protocol has acetylcholine testing performed after at least 24 hours of washout from calcium-channel blockers and nitrates; it states vasospastic angina is associated with sudden cardiac death, acute myocardial infarction, and syncope, and it contains no statement that beta blockers worsen spasm. Quotes are page-cited from the full text.]
9. Odanović N, Schwann AN, Zhang Z, et al. Long-term outcomes of ischaemia with no obstructive coronary artery disease (INOCA): a systematic review and meta-analysis. Open Heart. 2024;11:e002852. PMID: 39353703 [Finding: In a meta-analysis pooling 54 studies and 17,302 patients with ischemia and no blocked arteries, the vasospastic-angina group ran 0.7 deaths or heart attacks and 1.1 major adverse cardiovascular events per 100 patient-years. The authors call the overall rate low while reporting that microvascular angina, especially with reduced coronary flow reserve, ran significantly higher; heterogeneity between studies was high.]
10. Ford TJ, Stanley B, Good R, et al. Stratified medical therapy using invasive coronary function testing in angina: the CorMicA trial. J Am Coll Cardiol. 2018;72:2841-2855. PMID: 30266608 [Finding: In a randomized, blinded trial of 151 angina patients with no blockage, function testing with treatment matched to the result improved angina scores by 11.7 points at six months versus a sham procedure, with no difference in major adverse cardiac events at six months. The abstract does not report the endotype proportions; see reference 3.]
11. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and no obstructive coronary artery disease (INOCA): developing evidence-based therapies and research agenda for the next decade. Circulation. 2017;135:1075-1092. PMID: 28289007 [Finding: An ACC-convened working group's consensus statement; its full text reports that two US registry databases (ACC-NCDR and WISE) suggest at least three to four million women and men have signs or symptoms suggestive of ischemia with no obstructive coronary disease. A database-derived floor restated from two earlier papers, not a count, and not a count of spasm.]
12. Gulati M, Cooper-DeHoff RM, McClure C, et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med. 2009;169:843-850. PMID: 19433695 [Finding: Symptomatic women with normal coronary arteries had a five-year cardiovascular event rate of 7.9 percent, those with 1 to 49 percent narrowing 16.0 percent, versus 2.4 percent in age- and race-matched asymptomatic women from a separate community cohort; the abstract's phrase is "5-year annualized," and the full text's methods and Table 2 report them as five-year rates, with the authors describing the normal-artery group as "approximately 3-fold higher." Observational; "non-obstructive" is anatomic and broader than proven spasm.]
13. Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E. Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571-581. PMID: 23636227 [Finding: Two to three years after a first angiogram for suspected stable angina, persistent angina was present in 49 percent of patients with normal arteries and 64 percent with diffuse non-obstructive disease (1 to 49 percent narrowing) versus 41 percent with obstructive disease, and it carried higher odds of anxiety-range (OR 2.9) and depression-range (OR 4.3) screening scores. A questionnaire study with no provocation testing; it measures symptoms and mood scores, not who has spasm.]
14. Jespersen L, Abildstrøm SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study. PLoS One. 2014;9:e93170. PMID: 24705387 [Finding: Stable-angina patients with angiographically normal coronary arteries were hospitalized for cardiovascular disease about three times as often, and had repeat angiography 2.3 times as often, as symptom-free comparators. Same Danish research group as references 2 and 13; the figures are the normal-angiogram subgroup of an 11,223-patient registry, and the study had no artery-function testing.]
15. Kurabayashi M, Asano M, Shimura T, et al. Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test. Int J Cardiol. 2017;236:71-75. PMID: 28268085 [Finding: Taking amlodipine until two days before acetylcholine testing, the recommended washout, was independently associated with about a third the odds of a positive test (OR 0.327, 95% CI 0.125 to 0.858). Observational, one Japanese cohort; measured for amlodipine only.]
16. Rehan R, Wong CCY, Weaver J, et al. Impact of nitroglycerin administration on acetylcholine provocation testing in angina with nonobstructive coronary arteries. J Soc Cardiovasc Angiogr Interv. 2025;4(8):103668. PMID: 41019898 [Finding: In 40 patients with proven spasm, re-testing after nitroglycerin was given in the cath lab reproduced epicardial spasm in only 55 percent. Small, intra-procedural nitroglycerin rather than oral nitrate therapy; government-funded, with three of eight authors disclosing device-industry honoraria or research support.]
17. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565-2568. PMID: 26245334 [Finding: The COVADIS consensus definition of vasospastic angina, built from nitrate-responsive angina, transient ischemic ECG change, and documented spasm; the abstract does not state the angiographic threshold. A criteria statement, not primary data.]
18. Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16-20. PMID: 29031990 [Finding: The COVADIS consensus criteria for the investigative (research) diagnosis of microvascular angina: symptoms and objective evidence of ischemia, no obstructive disease, and reduced coronary flow reserve or inducible microvascular spasm. A criteria statement written for studies and registries, not primary data.]
19. Sato K, Takahashi J, Odaka Y, et al. Clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina: ethnic differences detected in an international comparative study. Int J Cardiol. 2019;291:13-18. PMID: 30819587 [Finding: In an international registry of 1,457 vasospastic angina patients, five-year survival free of major adverse cardiac events was 76.6 percent in Caucasian patients versus 86.7 percent in Japanese patients, with the Japanese arm 68 percent male and the Caucasian arm 51 percent. The Caucasian figure rests on 118 patients; the full text's Figure 1 legend defines the composite as cardiac death, non-fatal heart attack, hospitalization for heart failure or unstable angina, appropriate defibrillator shocks, and ventricular arrhythmia.]
20. Robertson RM, Wood AJ, Vaughn WK, Robertson D. Exacerbation of vasotonic angina pectoris by propranolol. Circulation. 1982;65:281-285. PMID: 6797752 [Finding: In a double-blind trial, propranolol given as sole therapy significantly prolonged the duration of angina attacks without significantly changing their frequency, and the authors judged it frequently detrimental for that use. The abstract gives no patient count.]
21. Shimokawa H. 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside. Eur Heart J. 2014;35:3180-3193. PMID: 25354517 [Finding: A single-author lecture, not a study, stating that the central mechanism of coronary spasm is hypercontraction of vascular smooth muscle, with Rho-kinase playing a major role by inhibiting myosin light-chain phosphatase, and explicitly "not endothelial dysfunction." It reports no new data; its abstract does not mention inflammation, senescence, or aging.]
22. Masumoto A, Mohri M, Shimokawa H, et al. Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation. 2002;105:1545-1547. PMID: 11927519 [Finding: In 20 patients with acetylcholine-provoked spasm, pretreatment with the Rho-kinase inhibitor fasudil (15 patients) versus saline (5) markedly attenuated the provoked constriction and prevented chest pain and ischemic ECG changes in all treated patients, without significantly changing systemic hemodynamics. Human, small, one center; randomization and blinding not described.]
23. Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046-1051. PMID: 3093861 [Finding: In 18 people in the cath lab, acetylcholine dilated the four normal coronary arteries (1.94 to 2.16 mm) but constricted all eight arteries with advanced narrowing (1.05 to 0.32 mm, temporary occlusion in five), and five of the six mildly diseased arteries also constricted, while all vessels dilated to nitroglycerin. The authors called the findings preliminary and read the paradox as a defect in the endothelium's ability to relax the vessel; this was a study of atherosclerosis, not of spasm patients.]
24. Ohyama K, Matsumoto Y, Takanami K, et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J Am Coll Cardiol. 2018;71:414-425. PMID: 29389358 [Finding: In 27 patients with acetylcholine-proven diffuse spasm of the left anterior descending artery versus 13 non-spasm controls, the fat around the coronary artery was larger, perivascular glucose-tracer uptake on PET was higher, more feeder vessels had grown in the artery's outer coat, and white-cell Rho-kinase activity was higher; on follow-up with medical treatment the PET inflammation signal and Rho-kinase activity both fell. Human, prospective, 40 people, one center, direction and significance only.]
25. Minamino T, Miyauchi H, Yoshida T, et al. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation. 2002;105:1541-1544. PMID: 11927518 [Finding: In coronary arteries from people who had ischemic heart disease, a senescence marker stained strongly in atherosclerotic lesions and not in the internal mammary artery, and the marked cells were endothelial; human aortic endothelial cells pushed into senescence in culture showed less eNOS activity and more of an adhesion molecule, changes that introducing telomerase inhibited. Autopsy tissue and cultured cells; atherosclerosis, not spasm; no numbers in the abstract.]
26. Donato AJ, Gano LB, Eskurza I, et al. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2009;297:H425-H432. PMID: 19465546 [Finding: In healthy men, older men's arteries opened less to acetylcholine and their lining cells made more endothelin-1, a constrictor (0.99 versus 0.57, a relative staining intensity, in 18 older versus 15 young men), while total eNOS was not reduced (P = 0.08, trend higher); the authors read aging as a shift toward constrictor signaling rather than loss of nitric-oxide machinery. Arm arteries in healthy men, not coronaries in spasm patients, plus a mouse experiment.]
27. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243-278. PMID: 36599349 [Finding: A framework review proposing twelve hallmarks of aging, defined by three premises, with cellular senescence and chronic inflammation among them. It supplies the lens this post uses to place spasm biology in aging terms; as a review it contains no data of its own and its abstract does not link any hallmark to coronary spasm.]
28. Boerhout CKM, Namba HF, Liu T, et al. Coronary function testing vs angiography alone to guide treatment of angina with non-obstructive coronary arteries: the ILIAS ANOCA trial. Eur Heart J. 2025;46:4396-4406. PMID: 40796241 [Finding: In 153 angina patients with no obstructive disease, all of whom had invasive function testing at their angiogram, disclosing the result and treating by a matched protocol improved the Seattle Angina Questionnaire summary score by 9.4 points at six months versus standard care, with no major adverse cardiac events in that window. A symptom and quality-of-life result, not an events result; the abstract does not say whether anyone was blinded.]