Managing the Complex Patient:
Diagnosis, Treatment, and Follow-Up
The second annual Circulate C-CHANGE Conference
Speaker Panel: Q & A
Frequently Asked Questions
Speaker: Peter Liu
Would Ivabradine slow down the AFib rate too? (Generally not, as Ivabradine mainly work on the sinus node. The general rule is that if the patient spends more than 20% of time in atrial fibrillation, i.e. out of sinus rhythm, then ivabradine is less effective)
Is it important to find out the reason why a pt has HFrEF? or assume it's ischemic? is there role for stenting/CABG for improving EF if it is ischemic? (Yes, it is generally a good idea, if the cause is unknown for a patient. This is because HFrEF has such a poor outlook, and any ways to correct the underlying cause, if not too late, makes a huge difference. This can indeed come from ischemia, where CABG or revascularization can improve outcomes, such as the STICH trial. Other causes include valvular disease, rhythm problems or tachycardia, toxins such as alcohol or chemotherapy, or untreated risk factors such as hypertension or diabetes, etc)
It sounds like Ivabradine and Entresto are not meant to be used together, is that correct? (Actually they can be used together, and in the PARADIGM trial, 11% of the patient received both medications, and they did very well. We don’t present them together in lectures, because they each target a different aspect of heart failure – ivabradine targets heart rate, while Entresto targets symptomatic instability with RAS activation, but their actions are complementary. So in the right patients with both indications, both can be used together with no problems)
How to identify patients in remodeling stage (This is hard to do clinically, we generally rely on imaging techniques like echo to determine how large the heart size is, whether there is left ventricular hypertrophy. Otherwise NTproBNP can also give us an indication of the heart size and stress/pressure in the heart. Knowing the remodeling helps to know the patient has HFrEF or HFpEF, and how advanced the condition is)
Speakers: Richard Choi and Sol Stern
Do you stop DPP-4s before starting clients on GLP1 ? Yes – DPP-4 inhibitors increase GLP-1 to physiologic levels by breaking down its usual degradation. GLP-1 receptor agonists deliver a much higher than physiologic level of GLP-1 by way of injection. So although it is not harmful to use a DPP-4 along with a GLP-1, it is redundant and should be stopped.
Are you still prescribing Glyburide for your T2DM clients? As a cardiologist, no. In terms of what I have seen and what primary care/Endos tell me – the first question is why use an SU (sulfonylurea) and the second question is – if you are planning to use an SU, then why Glyburide over another SU? SUs are inexpensive and effective (with more A1c lowering than SGLT2 or DPP4 agents!) so it is a good choice for glycemic control. It is however associated with weight gain and hypoglycemia whereas other agents are either associated with weight loss and low risk of hypoglycemia. There is also little evidence that SUs reduce MACE events (CV death, MI or stroke) unlike SGLT2, GLP-1 and perhaps Metformin. From Dr. Richard Choi If a decision is made to use an SU, Gliclazide and Glimepiride are safer and can be used at lower levels of eGFR. There is little price difference between the generic SUs. From Dr. Sol Stern: Although SUs are still in guidelines for people who cannot either afford or cannot tolerate other antihyperglycemics, I would prefer to use medications for which there is good evidence that outcomes such as cardiovascular disease and renal insufficiency are reduced (in addition to lowering blood sugars). I use very little SU in my practice and if I had to use an SU, I would prescribe Diamicron.
What about coronary artery calcification noted incidentally on CT? Is that generally considered in the definition of CVD as an indication for these medications? Coronary artery calcification is synonymous with coronary artery disease. There is no other reason to calcify your coronaries other than the presence of atherosclerosis. I generally view this is an ‘in-between’ category that is a little more than a primary prevention situation but not quite a secondary prevention situation. So I tend to treat these patients with statins to lower LDL to at least less than 2.0 mmol/L and the Canadian Lipid Guidelines from 2016 supports ‘consideration’ for this approach to treatment but feel that this ‘should be considered as less well studied indications for therapy’. The definition of established atherosclerotic cardiovascular disease (ASCVD) in the CV outcome trials with the DM agents did not include coronary artery calcification in the inclusion criteria. So although I do treat with statins, I do not consider them a secondary prevention patient in regard to the preferred indication for some antihyperglycemic agents according to Diabetes Canada guidelines.
Just to clarify. Asymptomatic non stenosing plaques or AAA's are not considered clinical Cardiovascular events based on your definition? Yes, you are correct. Here’s where it gets tricky. The Canadian Cardiovascular Society lipid guidelines have endorsed a secondary prevention approach for AAAs (over 3.0 cm in diameter) and for PAD if ABI < 0.9 (irrespective of symptoms). So I would regard these patients as somewhere in between primary and secondary prevention because they do not fit well in either category - but there is little data in such patients as they did not meet the definition of ASCVD for categorization or entry into the CV outcome trials for diabetes.
Since SGLT2 are having benefits on both heart and kidneys, knowing that DM is already considered high risk for both CVD and CKD, wouldn't it make sense to start the treatment for DM as initial treatment with SGLT2 or GPL-1 to prevent or delay the CVD or CKD?
From Dr. Richard Choi: To an extent, yes it would make sense. However, when providing guidance for treatment we can only make claims that are supported by published evidence and Health Canada approved indications. The European Society of Cardiology DM guidelines do recommend that for ASCVD, either or both SGLT2i/GLP-1s can be used ahead of Metformin. Diabetes Canada have not released guidelines or position statements indicating that these agents can be used ahead of Metformin. There is also now a Health Canada indication for Dapagliflozin for the prevention of heart failure but without notation that it is first line treatment. CREDENCE demonstrated renal protection with Canagliflozin but did not study the SGLT2i as first line treatment. So I think we should stick to the guidelines for most patients and wait for definitive evidence and guidelines updates. From Dr. Sol Stern: Metformin is still considered first line in treating DM unless there was a good reason not to, e.g. previous adverse effect or relatively low eGFR. My understanding is the evidence for metformin reduced cardiovascular events is not as strong as the evidence of other antihyperglycemics. Therefore, personally, I think it makes sense to start initial treatment with SGLT2 Inhibitors of GLP-1 agonists especially if the patient is known to have CAD and is on no other antihyperglycemics.
Is there an age limit beyond which the benefits of these meds is unproven? The CV outcome trials with SGLT2/GLP-1 agents did not have an upper age limit on inclusion. There are subgroup analyses on study subjects by age, usually either older/less than 65 or in one trial older/less than 60 years of age. There was no statistical difference in the benefits on MACE in older vs younger patients. This does not completely answer your question but I would think that an older patient should be eligible for consideration of these agents given that the benefits were realized over a short duration of time (within the trial) and that the medications were well tolerated.
When starting SGLT2 or GLP1RA, do you stop any of the patient's anti-hyperglycemic meds or can they just be added on?
From Dr. Richard Choi: You should stop DPP-4 when starting a GLP-1 RA for reasons answered in a previous question.I generally do not stop or adjust any of the other anti-hyperglycemic medications except in certain circumstances. They have a low risk of hypoglycemia unless the patient is on insulin or insulin secretagogue (i.e. sulfonylurea). So I generally look at the A1c and if more than 1% above target, I simply add on. In some cases, where the A1c is close to target or even below target, I have essentially ‘switched’ meds and stopped one agent to allow for ‘room’ on the A1c to permit prognosis altering medications like the SGLT2/GLP-1 classes to be given. This usually tends to be an SU which for multiple reasons I believe can be justified. From Dr. Sol Stern: It depends on what the A1C is . If they are already at target and you are adding the medications for cardiovascular protection, you may be able to replace the initial medication . If the A1C is not at target, you may want to simply add the new agent and monitor them.
8. I started a patient at a1c 8% on Ozempic, after 3 months at 0.5 dose but no change despite proper use - any advice? The first thing I would think of is adherence. Are they taking the medication and how is their injection technique. I would also ask them about diet and exercise and alcohol intake. If all OK, I would increase the dose to 1 mg weekly and see if that is effective.
9. Will a single GU infection in a patient force you to stop using SGLT2 inhibitor in the future for that patient? I would not stop the SGLT2 inhibitor after a single GU infection. I might stop it for recurrent or relapsing infections. I think the benefits especially in cardiovascular disease outweigh the nuisance of a GU infection.
Speaker: Paul Oh
1. Your comment on intermittent fasting will trigger stress hormones which could be harmful to heart and endocrine system
I believe that it depends on how extreme the fasting protocol might be. You are correct that there are reports that suggest increase in tress hormones like cortisol with extreme fasting. However, the current popular models ("16:8" or a "5:2") may be kinder on the cardio metabolic system. 16:8 refers to 16 hours of fasting with 8 hours of regular eating which for many people is only a slight variation on a typical day that includes 3 meals, but trying to tighten eating behaviour to a better balanced circadian rhythm (i.e., don't eat at night). 5:2 refers to 5 days of regular eating and 2 days during which calorie intake is restricted to 500–600 per day; definitely lower intake but not complete starvation. The primary authors behind these approaches also emphasize overall healthy nutritional content: more fruits and veggies, fibre, healthy protein, and fats, and avoid sugar, refined grains, processed foods (like Mediterranean pattern). I'm not aware of major excess adverse cardiac events that have been reported. There is evidence of improved control and lower insulin resistance in people with diabetes. For some people fasting is tough though on a practical basis.
Here is a link to a well written blog about the topic:
Intermittent fasting: Surprising update - Harvard Health Blog - Harvard Health PublishingConsider a simple form of intermittent fasting. Limit the hours of the day when you eat, and for best effect, make it earlier in the day (between 7 am to 3 pm, or even 10 am to 6 pm, but definitely not in the evening before bed). Avoid snacking or eating at nighttime, all the time. Effects of intermittent fasting on health, aging, and disease ...www.health.harvard.edu
And here is a link to a review on intermittent fasting in the NEJM:
Effects of Intermittent Fasting on Health, Aging, and Disease | NEJMEffects of Intermittent Fasting on Health and Aging Evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base...www.nejm.org
2. Is there a comprehensive program (exercise, behavioural, nutritional) available to patients at high risk?
Many cardiac rehab programs in Ontario (depending on overall capacity) will accept some patients in a high risk primary prevention program (diabetes, hypertension, dyslipidemia, family history, smoking etc.). At UHN about 15% of our clients fit into this category.
Speaker: Robert Myers
Q1. Baseline investigations
I recommend a 24 or 48 hour Holter monitor for all new onset atrial fibrillation. This helps determine if there is a paroxysmal component during monitoring, the presence of other arrhythmias and the average heart rate which helps guide therapy.
Patients with atrial fibrillation should have a screening echocardiogram. If there are no other symptoms of heart disease, atrial fibrillation is not an initial manifestation of CAD when it occurs in isolation. Therefore I don’t routinely order a stress test, and would only do a stress test if I was looking for the heart rate response to exercise during the arrhythmia.Though thyroid testing is often done, in the rare circumstance that hyperthyroidism is causing atrial fibrillation, it would be clinically apparent. The patients I order TFTs on are younger without any other explanation.
I don’t routinely order a CXR for patients with atrial fibrillation
Re: CHADS2VASC2 this is a CCS guideline I am cautious about, so it comes down to personal preference. I am not impressed with the conclusion that all patients over 65 receive OAC as there are no relevant studies to support this. American and European (UK) guidelines recommend CHADSVASC2.
Q3. NOAC (DOAC) and mechanical heart valves
In the phase II RE-ALIGN trial of dabigratan and Coumadin, the trial was stopped due to excess bleeding and strokes in the dabigratan group. Based on this trial NOACs are absolutely contraindicated for mechanical valves. There has been criticism that further studies should be considered as the trial was insufficient to draw this conclusion.
Q4 DOAC (NOAC) and mechanical heart valves
Direct oral anti-coagulants (DOAC) also known as novel oral anticoagulants (NOAC) are only contraindicated in patients with mechanical heart valves.
CO-CHAIRS: Sheldon Tobe, MD and Rahul Jain, MD
Richard Choi, MD, FRCPC
Staff Cardiologist at Unity Health Toronto
Dr Rahul Jain, MD, CCFP, MScCH (HPTE)
Family Physician and Hospitalist, Sunnybrook Health Sciences Centre
Assistant Professor, University of Toronto, Department of Family and Community Medicine
Peter Liu, MD, FRCPC
Chief Scientific Officer/ Vice President, Research, University of Ottawa Heart Institute
Director, Cardiac Function Laboratory, University of Ottawa Heart Institute
Professor, Faculty of Medicine, University of Ottawa
Professor, Faculty of Medicine, University of Toronto
Robert Myers, MD, FRCPC
Cardiologist, Division of Cardiology, Sunnybrook Health Sciences Centre
Assistant Professor, Department of Medicine, University of Toronto
Director of the Rapid Cardiology Assessment Clinic, Sunnybrook Health Sciences Centre
Paul Oh, MD, FRCPC
Scientist, Toronto Rehabilitation Institute (TRI)
Associate Professor, Department of Medicine, University of Toronto
Medical Director, Cardiovascular Prevention and Rehabilitation Program
Research Division Head, Toronto Rehabilitation Institute (TRI)
Sol Stern, MD, MSc, MCFP
Family Physician, Argus Medical Centre
Dr. Sheldon Tobe, MD, MScCH (HPTE), FRCPC, FACP, FAHA
Nephrologist, Division of Nephrology, Sunnybrook Health Sciences Centre
Professor of Medicine, University of Toronto, Northern Ontario School of Medicine
Nephrologist Sunnybrook Health Sciences Centre
Subodh Verma, MD, PhD, FRCSC, FAHA
Professor and Cardiac Surgeon, University of Toronto
CRC Chair in CV Surgery, St. Michael's Hospital