Sep 27 2024 This Week in Cardiology

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In This Week’s Podcast

For the week ending September 27, 2024, John Mandrola, MD, comments on the following news and features stories: Surgical clearance, nonischemic cardiomyopathy (NICM) assessment, dueling perspectives on percutaneous coronary intervention (PCI) as first-line therapy for angina, guideline directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF).

New ACC Peri-operative Guidelines Released

The Journal of the American College of Cardiology (JACC) has published a lengthy guideline document on perioperative management for non-cardiac surgery (NCS). I would like to say a few words on this because it comes up nearly every day.

We are asked to provide “surgical clearance” for one of our patients. This phrase, surgical clearance, may be the most ridiculous phrase in all of modern medicine.

I don’t write this nor do I say it, but I think to myself, only God can clear someone for surgery.

The notion inherent in the surgical clearance phrase is so preposterous that anyone who utters it ought to wear a sign saying, “I am a soft thinker.” It is as if the requester of clearance believes that a cardiologist will render the patient free of complications. Indeed, the patient may have no complications after surgery, but it is hardly due to anything the cardiologist did.

Listeners outside the United States may not have such problems of pre-op clearance, but we waste a lot of money evaluating people before surgery here in the United States.

The guideline document, like all such documents, is massive and well -referenced.

One suggestion I have would be to make a section or Table on randomized controlled trials (RCTs) in the therapeutic space. This would make it easier for a user to know when an RCT vs observational data supports a recommendation. It’s nearly all observational data.

A couple of specifics. This is a quote from the summary document:
Stress testing should be performed judiciously in patients undergoing NCS, especially those at lower risk, and only in patients in whom testing would be appropriate independent of planned surgery.

The authors only have two recommendations on stress testing. One is a 2b level of evidence B-NR (Observational study only). This is for patients with poor functional capacity and high peri-operative risk. Stress testing may be considered to evaluate for ischemia.

But the authors also write in the text that, “the goal of preoperative testing for ischemia is not to identify undiagnosed CAD (coronary artery disease) but to identify patients for whom revascularization is believed to improve clinical outcomes, specifically those with left main disease or severe multivessel disease with a reduced LVEF.”

Right after that sentence the authors cite an observational study finding that centers with high levels of stress testing before abdominal aortic aneurysm (AAA) repair had no better outcomes than centers with low stress testing.

The value of routine stress testing before AAA repair should be reconsidered, and stress testing should be used more selectively, given these findings and the associated costs of widespread testing.

The ACC authors also write:

“However, an abnormal stress test should not prompt coronary angiography or revascularization unless the study has high-risk features.”

This goes back to the classic RCT, called CARP, by McFalls and colleagues in 2004, which had nearly 6000 patients with significant CAD who had major vascular surgery. They looked at revascularization vs no revascularization before surgery.

There were zero differences in mortality. Except the revascularization group had a 36-hour delay before surgery.

The ACC authors also give a Class 3 No Benefit recommendation for stress testing.
In patients who are at low risk for perioperative cardiovascular events, have adequate∗ functional capacity with stable symptoms, or who are undergoing low-risk procedures, routine stress testing before NCS is not recommended due to lack of benefit.

Another specific comment on the matter of risk scores. I had no idea there were seven different risk scores. I “clear” at least one or two patients for surgery a day and I have never needed a risk score. Here is why: if the patient is not having cardiac symptoms, there is no need for testing and surely no need for revascularization.

If a surgeon recommends surgery, first I assume that he or she knows what they are doing. So, I let the patient have surgery. I have a note saying that there is no modifiable testing necessary, etc.

In two situations I speak with the surgeon on the phone. One is if the patient is high risk to interrupt oral anticoagulation (OAC) Say, previous stroke, isolated left atrial appendage (LAA), or mechanical valve. I ask the surgeon, Hey, are you sure surgery is required or highly beneficial, or can you do it without interrupting OAC? Obviously, brain and bone surgeons need interruption of OAC, but I’ve been surprised that a lot of surgeons will do surgery without OAC interruption if informed about risk.

The second reason I speak with surgeons is when the patient is super sick — usually nearing end of life. I say in a gentle way that this patient has days to weeks or weeks to months. Are you sure surgery will be helpful?

Nearly every other case of cardiac disease (I don’t deal with congenital disease) can make it through surgery, if a surgeon says they have to do it.

A risk score telling me that the risk is 12% vs 20% doesn’t matter. People can’t put these numbers into context. (by the way, this is why coronary artery calcium [CAC] doesn’t help statin decisions much. Can a normal factory worker or carpenter or whoever tell the difference in risk between 7% and 12% over the future 10 years.

Another specific comment. There is section on operating on patients with left ventricular assist devices (LVADs). I don’t get it. I would say, -a) don’t operate on these patients and b) if surgery is that necessary, do it at an HF center and make sure the LVAD team is there with you.

These caveats aside, the document contains a lot of practical information about specific scenarios. For instance, there is a table about handling direct OAC interruption. It’s a nice table, though all one needs is a decent understanding of pharmacology, which any cardiologist should be facile with. They are conservative regarding bridging with heparin, which is way overdone.

There are comments on holding GLP1 agonists for days before anesthesia because of delayed gastric emptying. That is surely a new problem. And not a small thing for those patients who require urgent surgery. Message: all medical interventions have potential downsides. You know, like the patients with stable CAD who gets kissing stents in a proximal bifurcation who has to hold antiplatelets for spine surgery a year after the PCI.

I’d love to hear from you all on pre-op management. Am I doing it wrong?

NICM – We May Be Doing it Wrong in Selecting ICDs

I’ve spoken often on this podcast about the negative trials of implantable cardioverter defibrillator (ICD) use in patients with NICM. DANISH was the most recent, but recall that DEFINITE was also negative, as was the NICM-subgroup in SCD-HeFT.

The thing is that all these studies — in fact, every single trial for ICD use in primary prevention — uses LVEF as the risk stratifier. LVEF of 34% and an ICD is indicated; LVEF of 36% and ICD use is fraud.

I say it this way to emphasize the folly of arbitrary EF cutoffs. But there is another problem with LVEF as the main risk indicator — it’s pretty lousy. While low EF confers a higher relative risk for ventricular fibrillation, most events occur in patients with higher EFs in the non-ICD eligible range.

Back when ICD trials were done, LVEF is all we had. Times have changed. We now use cardiac magnetic resonance imaging (CMR). CMR allows for all that an echo can do (EF, valvular function) but CMR allows us to characterize tissue. Late gadolinium enhancement (LGE) represents the reference standard for noninvasive assessment of focal replacement fibrosis — scar. 

While CMR offers other ways to characterize tissue, I am not an imager and will focus mainly on the role of LGE — also known as scar.

Scar in the myocardium sets up the milieu for arrhythmogenesis because reentry requires 3 things: two pathways, slowed conduction in one, and unidirectional block.

JAMA has published a comprehensive meta-analysis of studies looking at risk stratification in NICM using CMR imaging. First author Christian Eichhorn.

Meta-analyses have their limits, but I think this one is useful because there are so many papers describing LGE and future risk in patients with NICM.

• Eichhorn’s team found 103 studies including nearly 30,000 patients with dilated NICM.

• Many of these studies were single-center reports. Only half were prospective; mean duration 3 years. Patients were young at age 55 years; mean LVEF 30%.

• Main outcome measures were all-cause death, cardiovascular (CV) death, arrhythmic events, HF, and major adverse cardiac events (MACE).

The results:

96 of the 102 studies reported on the association between LGE presence and clinical outcomes. In general, LGE presence is bad.

• Hazard ratio (HR) for death, 1.81 (95% confidence interval [CI], 1.60-2.04]; P < .001).

• HR for CV mortality, 2.43 (95% CI, 2.13-2.78; P < .001).

• HR for arrhythmic events, 2.69 (95% CI, 2.20-3.30; P < .001).

• HR for HF events, 1.98 (95% CI, 1.73-2.27; P < .001).

• HR for MACE, 2.09 (95% CI, 1.79-2.44; P < .001).

LGE extent also predicted events. Per 1% higher LGE extent:

• For all-cause mortality (HR, 1.07 [95% CI, 1.02-1.12]; P = .02).

• For cardiovascular mortality (HR, 1.15 [95% CI, 1.07-1.24]; P = .01).

• For arrhythmic events (HR, 1.07 [95% CI, 1.03-1.12]; P = .004).

• For heart failure events (HR, 1.06 [95% CI, 1.01-1.10]; P = .02). 

• For MACE (HR, 1.03 [95% CI, 1.02-1.04]; P < .001). 

Not so much for per 1% LVEF improvement.

• The authors found no significant association with all-cause mortality, CV death, arrhythmic events per 1% higher LVEF. They did see slightly lower HR for HF and MACE per 1% higher LVEF.

Extracellular volume fraction, T1 relaxation times, and global longitudinal strain (GLS) had less available data to make reliable associations with death or CV death.

Meta-Regression:

• The association between LGE presence and all-cause mortality was significantly modified by patient age (P = .001), gender (P = .004), and baseline LVEF (P = .02).

• Stronger associations were seen in populations of younger patients, with more severely impaired systolic function and higher proportions of male participants.

• Interesting was that baseline LVEF did not modify the association between LGE presence and cardiovascular mortality, arrhythmic events, heart failure events, and MACE.

Authors’ Conclusions:

The presence and extent of LGE were associated with various adverse clinical outcomes, whereas LVEF was not significantly associated with mortality and arrhythmic end points in NIDCM. Risk stratification using native T1 relaxation times, extracellular volume fraction, and global longitudinal strain requires further evaluation.

Comments. I must admit a weakness in imaging, so I want to tread carefully. But it seems clear to me that times are changing.

This comprehensive review makes it clear that the presence and extent of LGE is a clear marker of high risk. It also exposes the limits of risk stratification with LVEF. Higher EFs associate with less HF and less MACE but having a higher EF did not confer lower risk of death, CV death, or arrhythmia. GLS underperformed but there was little data.

One criticism I hear when I reiterate how we as a field ignore the negative NICM trials — especially DANISH — is that these trials enrolled a lower risk and highly heterogenous population. NICM comes in many different varieties. This review shows that CMR ought to be a much better predictor than LVEF.

And if we enrolled patients with high LGE to ICD vs no ICD we would likely show ICD benefit. In fact, the authors tells us that two such trials are ongoing: The German led CMR-ICD (NCT04558723) and the Southampton led BRITISH (NCT05568069) studies are open-label, government-funded trials randomly assigning patients with NICM who have LVEF ≤35% and evidence of LGE on CMR imaging to receive either primary prophylactic ICD implantation or optimal medical therapy only, with all-cause mortality as the primary end point.

There are aspects of the ICD story that have been ugly: The Heart Rhythm Society caving to industry to allow non-EP docs to learn ICD implantation during weekend courses when the seminal trials came out; our resistance to find better risk stratification tools for 2 decades; the general failure of key opinion leaders and guideline writers to emphasize the concept of competing risks of death (resulting in scores of frail elderly patients getting ICDs); and the total failure to incorporate the negative DANISH trial into guidelines. I do like where we are going with the LGE-guided approach to ICD use.

Patients with newly diagnosed NICM often have CMR. They probably ought to have CMR, though that could also be studied empirically. Then we randomize patients with LGE positive or LGE negative to ICDs or medical therapy.

There is a chance ICDs will prove helpful in patients with LGE. But there is a chance that event rates will be too low, and medicines too good for an ICD to prove beneficial. I for one hope that the two ongoing trials enroll enough patients so that we don’t have wide CI and we actually get an answer.

Kudos to the Swiss led team who did this impressive meta-analysis.

When Should PCI Be Used in Chronic Stable CAD?

We know PCI does not reduce myocardial infarction (MI) or death in patients with stable CAD. We should therefore not do it to relieve fear of doctor or patient. ,  I think that is why most PCI of stable disease is done — namely, that these lesions look so gnarly.

But let’s say we lived in a world where everyone was enlightened and used the COURAGE, BARI-2D, and ISCHEMIA trials. We would still have patients with 80% coronary lesions who have angina. Real angina. Not fatigue. Not funny shortness of breath while sitting down, not premature ventricular contractions, not paroxysmal atrial fibrillation. Real angina.

The patient is on statin and aspirin and has stopped smoking. Disease modifying treatments are ongoing. But he simply cannot do much because of angina. It’s a pesky situation.

There are now two choices. You could maximize anti-angina meds.  Nitrates, beta- blockers, perhaps ranolazine.

The other option is to say, screw the tablets. Just do PCI and stent it.

The debate and choice come up because of the placebo-controlled ORBITA-1 and ORBITA -2 trials. ORBITA-1 found that if you maximize anti-anginals, PCI adds no significant advantage over a placebo procedure. ORBITA-2, however, took patients with angina who were treated with anti-anginals, then stopped the antianginals, then randomly assigned the patients to PCI or a placebo procedure. In this case, PCI had a placebo-resistant effect on quality of life (QOL) and exercise time.

Dueling essays in Circulation Outcomes made different arguments. Christopher Rajkumar and Rasha Al-Lamee argue that using PCI as it is in the guidelines — for patients whose angina is not controlled on meds — selects for a scenario where PCI is least likely to benefit. The reason probably relates to the fact that patients with persistent symptoms on maximal medications likely have a non-ischemic cause of symptoms. So, fixing the obstruction is unlikely to have a physiologic effect but rather a placebo effect.

They argue, rightly, that both meds and PCI are strong anti-angina agents, and whichever is used first seems to saturate all the benefit. Since either a medication first or PCI first strategy should also be combined with disease modifying treatments (statin, aspirin, not smoking, fewer donuts, etc), the choice could be discussed with patients and become a preference-sensitive decision.

I have no doubt that at Imperial college London there are great discussions wherein it is made clear to patients that PCI does not make them safer from death or MI, that PCI comes with the need for long-term antiplatelets, that there will also be a metal cage in the artery, and that PCI has procedural risks. But they would also explain to patients that if you are to have an elective procedure, it makes sense to take those risks when the odds are highest it would help, and that is when you do PCI upfront.

Bill Boden and Raffaele De Caterina make the case that ORBITA trials do not justify the promotion of PCI-first strategy. They call the ORBITA trials small, which is true but not really. True in that they were smaller than outcomes trials like COURAGE, but ORBITA trials enrolled enough patients to sort out continuous outcomes of time on a treadmill vs placebo.

Boden and De Caterina make seven points:

1. ORBITA 2 was already known, as ACME had shown plain old balloon angioplasty was better than tablets.

2. Not all angina is due to obstructive disease. Thus, a PCI-first strategy targeting epicardial disease may miss microvascular dysfunction.

3. The PCI-first strategy exposes a lot of patients to procedure complications

4. Symptoms persisting after maximizing anti-anginal meds should not always be considered a failure of therapy but a failure to diagnose the proper problem. Meaning the target may be non-epicardial disease such as vasospastic angina or microvascular dysfunction

5. They disagree with the sub-analyses of ORBITA-2 that found that patients with typical angina had greater PCI responses.

6. The ISCHEMIA trial found no penalty to deferring PCI. And QOL scores eventually — within 1 or 2 years— come together. This is true and seen also in COURAGE, which found no QOL difference at 3 years.

7. They are very skeptical that shared decision making will lead to truly shared decision. Rather shared decision making will be used to justify doing PCI.

They conclude:

In summary, rather than decrying the view that current clinical guidelines set PCI up to fail, we strongly argue that a PCI-first strategy targeted largely to symptom control potentially diverts attention from years of progress in improving event-free survival with robust secondary prevention and lifestyle intervention.

If, on the basis of the short-term outcomes of the ORBITA trials in selected patients, clinicians choose PCI as the initial approach to management and perhaps become complacent or agnostic to the need for comprehensive secondary prevention and lifestyle intervention, such a shift in management could, in turn, set OMT up to fail with long-term detrimental consequences for our patients.

My take. If you are a Neutral Martian working in an environment where PCI was not incentivized financially and where PCI wasn’t considered super cool, I would side strongly with Imperial college. Clearly PCI provides a placebo resistant effect in a medicine-free state. My siding with this argument not only assumes a Shangri-La-type state of affairs but also that Imperial college-like people talk with their patients; that patients understand that angina therapies seem to make no difference at 2 to 3 years, perhaps because of collateral vessels; that PCI means taking an extra pill (an antiplatelet med) perhaps forever; that interrupting it confers risk of stent thrombosis; that PCI trades one disease for another. I for one would probably choose tablets because I have a fear of having metal in my proximal LAD or RCA.

But Boden and De Caterina have good points. I am in 100% agreement with their skepticism regarding shared decision-making. This will fail miserably in the United States. I will bet you my Canyon AeroRoad bike that in the United States, the vast majority of patients will take PCI-first because the doctor will favor that.

I also agree with the idea that PCI first could lead to less use of disease modifying therapies, though that is no fault of ORBITA team. They clearly advocate for disease modifying therapy.

Finally, in many places in the United States, we essentially have a PCI-first approach, because so few patients with stable CAD who have PCI are a) having angina, or b) on proper antianginals. Therefore, a guideline change allowing PCI-first after shared decision-making would have little effect on PCI use in stable CAD because the number of patients with high grade stenoses leaving US cath labs without stents approaches zero.

The essays are good. Go read them.

GDMT Underuse in Patients with HFrEF

JACC HF haspublished a nice research letter, first author, Stephen Greene, MD, from Duke, looking at physician reported reasons for not initiating GDMT in patients with HFrEF.

They used data from something called Adelphi Real World HF Disease Specific Program which is a survey of cardiologists and primary clinicians in the US.

Caregivers reported data for up to five consecutive patients with HFrEF (<40%) seen in the outpatient clinic.

For these patients who were not on full-gas GDMT with the four classes of drugs, clinicians were asked to choose a primary reason from a multiple choice response.

The research letter reported data from 86 docs(53 cardiologists and 33 primary care).

There were 323 patients, median age 67 years, half with Medicare, a third with commercial insurance, and some with Medicaid or Veteran’s administration coverage.

Median systolic blood pressure (BP) was 126; median creatinine 1.1; potassium, 4.2.

Results:

• 85% were not on full gas quadruple therapy.

• For angiotensin receptor/neprilysin inhibitor drugs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, the most common physician-reported reason for not initiating medication was that the patient was “clinically stable and/or had adequate symptom control” (43% to 55% of instances).

• Patient preference was listed at 7% to 13%; high out-of-pocket costs, 2% to 14%; low blood pressure, 7% to 10%; kidney dysfunction, 0%-9%; previously proven intolerance, 1% to 9%, and current/recent hyperkalemia, 0% to 4% were reported as the primary reason in a minority of cases.

Comments. I can already hear the proponents. This is terrible. Bad doctors. Lazy doctors. We need a stick not a carrot. We need education.

Well, let’s start with the limitations. This is a small sample. I don’t know what the Adelphi Real World Heart Failure Disease Specific Program is. It’s also not clear if these patients were similar to the patients in trials.

The authors don’t tell us about the median EFs. That is huge, because if I have a patient on three drugs who has no symptoms and an EF of 39%, I might not push it. Take DAPA HF. All patients had Class 2 or greater symptoms. The median EF was 31%. In RALES, 90% of patients had class 3 or 4 HF and the mean EF was 25%.

So, I want to tell the HFrEF scolds to stand down a bit. I want to know more about these patients.

I don’t see many patients like those in trials who are not on or who have not been tried on all four drug classes.

But I also think the letter is on to something. Clinical inertia is real. It’s not always a bad thing. Regular doctors are in a constant struggle every single day to help patients maximize their health and minimize the impact of treatment. Our aim is to help people but also allow them to be people rather than patients.

Every time a doctor walks into an exam room, he or she faces the Icarus analogy. You could be a dumb robot and keep pushing guidelines and forcing patients to spend more time doing medical things, and in the process incur harm and perhaps lose trust if that happens. Or, you could get to a happy place where things are good enough and the patient is happy but perhaps the data-extractors are not.

Another factor is that so much of HF therapy is preference sensitive. For patients who are maximizers, they are happy to titrate up. They have their notebooks and spreadsheets and love their BP cuff. Fine. Push on.

But lots of patients are minimizers. They don’t have a BP cuff. Or an easy ride to the clinic. A little lisinopril and carvedilol well under the risk margin is good enough. That is not bad medicine. That is good medicine. You give this patient painful breasts and he won’t think much of you.

Anyway, I am always happy to hear how you feel.