Methamphetamine Associated Heart Failure (Gordon, 10/8/25)

 A recording of this presentation is available HERE.

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Thanks so much to Dr. Lily Gordon for a really impactful presentation on Methamphetamine Associate Heart Failure. We see SO much of this condition in the hospital, and at times it can literally feel like the Wild West. Having a structured presentation helped me to understand where to focus my medical an advocacy efforts, as well as contextualizing the problem within our current times. 

Epidemiology and Trends

For example, it was helpful for me to hear that methamphetamine use rates have increased significantly in the last decade (see graph below), that the entire west coast is experiencing an disproportionate burden of meth-induced heart disease (see map below), and that patients with meth-induced heart failures have a documented longer length of stay and higher cost and disease burden. 

My lived experience as a hospital-based family doctor was confirmed that patients with this disease carry a high burden of social determinants of health, including housing instability and low SES, as well as disease occurring at a younger age and male-gender predominant.  

I was fascinated to revisit the physiology and pathophysiology of meth-induced heart failure to be able to understand that there are two dominant pathways through which methamphetamine impacts cardiac output, leading to heart failure: 1) direct myocyte toxicity as well as 2) sympathetic activation. 

Interestingly, for patients who use methamphetamine, binge pattern of use (leading to higher rates of inflammation), co-use with alcohol (even in low and moderate range), and an as-of-yet undiagnosed genetic predisposition are associated with meth-induced HF, whereas route of use (IV vs. smoke vs. snort) and duration. This has also been my experience-- that some patients can use for decades and not develop cardiomyopathy, whereas others can use in binge-like fashion for a relatively short period of time (less than a year) and develop heart failure. 

Diagnosis and Treatment

A reminder from Dr. Gordon that Meth-associated Heart Failure is a diagnosis of exclusion. There are no consensus guidelines on diagnostic criteria. In point of advocacy, patients with a new diagnosis of heart failure AND concomitant meth use tend to have a longer delay in getting an ischemic evaluation, as shown in the data from this 2024 paper from Kersey, et al (see below). A reminder that most patients with a new HF diagnosis should get an ischemic evaluation as part of their diagnosis.

Another important clinical pearl is that something like 33% of patients with meth-associated HF have an LV thrombus, and transthoracic echocardiogram is only 21-35% sensitive in detecting these. For patients with otherwise unexplained worsening of symptoms and/or diagnosis, some professional organizations recommend cardiac MRI vs. contrast-assisted ultrasound in order to properly diagnose LV thrombi. 

 

Three patient-centered questions:

1) Is the damage from methamphetamine permanent?

answer: limited data from Germany (Schurer, 2017) found that the ejection fraction in patients with hear failure OFTEN improves significantly with meth cessation (as compared with continued use). This, in my opinion, may offer our patients some true HOPE. 

2) Are there treatment options to help me stop meth?

answer: there is good data that CONTINGENCY management (i.e. payment/gift cards and/or rewards) is the most effective intervention to decrease methamphetamine use and get to sustained cessation. 

Non-FDA approved (but evidence based) interventions that can be effective in helping with meth cessation include naltrexone+ bupropion (contraindicated with concomitant opioid use), mirtazapine (ideal for co-treating depression), and psychostimulants (in case of underlying ADHD).

3) What if I cannot stop?
answer: GDMT is still indicated and can improve outcomes. Patients with ongoing methamphetamine use should still be offered full GDMT. We could do better! Active meth use is not reason to withhold lifesaving treatment. The chart below shows evidence that we can be more diligent about providing full GDMT for these patients. 

Pulmonary Hypertension (Wang - 8/2/23)

 A recording of this presentation can be viewed HERE.

***

Dr. Helena Wang gave an excellent Grand Rounds this week on Pulmonary Hypertension. It is worth watching!

We currently have at least three patients on our adult medicine service that we are evaluating for this condition after getting a TTE to look at their heart failure status. Pulmonary hypertension is such an interesting intersection between the lungs and the heart and a good opportunity to review basic physiology too! Dr. Wang gave an earlier version of this presentation 2 1/2 years ago, and I felt then, as I did this week, that I could watch it over and over. You can! 

But for those who prefer the written word:

The definition of pulmonary hypertension (pHtn) is simple enough: a mean PAP of > 20mmHg at rest.

Dr. Wang likens the pulmonary artery to something like a six lane highway (think of the 101 going north from Novato into Petaluma). When the lanes decrease from six to two in northern Novato, there is suddenly a lot of congestion, and all the cardiac output has to move through that smaller space at higher pressures. Voila! Elevated PAP.

Pulmonary arterial hypertension is rare, but not that rare, 15-50 cases/million, and more common in people with HIV (regardless of CD4 count or duration), connective tissue disease, and portal hypertension. For patients with any of these diagnoses, should be screened annually for pHtn with an echocardiogram (TTE).

Symptoms of pHtn include dyspnea on exertion, fatigue, edema, bloating, and syncope (obviously pretty non-specific). 

On exam, you can see elevated JVP (check the neck veins!), hear a split S2, and see peripheral edema.

Chest imaging reveals often a dilated R pulmonary artery on CXR, and even sometimes a prominent L pulmonary artery. Also, look for the "banana and egg sign" on CT, in which the aortic arch and the pulmonary artery are a little too close in size for comfort. The aortic arch is the banana; the pulmnoary artery is the egg.

Banana and egg sign (photo credit: CHEST Journal)

Okay, what about the TTE??

Oh, reminds the pulmonologist and the family physician, don't forget to pay attention to the right side of the heart in the echocardiogram! Dr. Wang urged us to scroll down, skip the conclusion,  and look at the text (often the third paragraph). Is the RV big? What is the velocity of the regurgitant jet? What is the TAPSE?

A first hint of pulmonary hypertension on a TTE comes on apical 4 chamber view where the R ventricle shows turbulent flow back into the R atrium

RVSP (right ventricular systolic pressure) is an estimate reported on most echo reports and can be very challenging for the Echo tech to calculate. However, a calculated RVSP>25 is considered HIGH right sided pressure and increases your suspicion for pHtn.

The R ventricle is often very plump and dilated under high pressure (so. . .a big chubby RV on echo is another clue that you might have pulmonary hypertension)

Tricuspid Annular Plane Systolic Excursion (TAPSE): RV contracts in a twisting motion with each contraction as RV shortens. Normal excursion is 1.5cm. If RV is volume overloaded and dilated, cannot squeeze as well, not shortening, TAPSE drops <1.5cm on echo

And finally, right heart catheterization is still gold standard for measuring R sided pressures, but really this should be done after you have done a full evaluation (see below) once you are pretty certain you have primary pulmonary hypertension (WHO Group 1). And, due to changes in insurance, it is no longer required always for diagnosis.

WHO Classification of Pulmonary Hypertension

• WHO Class 1: Pulmonary ARTERIAL Hypertension (pressure goes up, fluid backs up)
• WHO Class 1 has the worst outcome: 5 year survival 61%
• only diagnosed once other causes of pulmonary hypertension are identified and treated
• Seen in patients with HIV (regardless of viral load, duration), connective tissue disease (e.g. scleroderma), and portal hypertension
• All other WHO classes are actually pulmonary VENOUS hypertension (something downstream to the lungs causing poor forward flow, back up of blood, then high pressure on R side of heart). These include
• WHO 2: L heart disease (LV systolic or diastolic dysfunction, valvular disease, s/p TAVR, myxomatous disease)
• WHO 3: bad lung disease or hypoxia (COPD, inadequately treated asthma, ILD, sleep disordered breathing (OSA), OHS, chronic exposure to high altitute, developmental lung disease. Consider high resolution CT (with very thin cuts with and without contrast), home sleep test, pulmonary function tests.
• WHO 4: chronic thromboembolic pulmonary hypertension (small, little tiny chronic). You cannot see this on typical PE protocol CT scan. You need a VQ scan to evaluate chronic thromboembolic disease.
• WHO 5: potpourri

Once Pulmonary Hypertension is identified, the next question is DOES the patient have pulmonary hypertension that is primary or secondary

Ddx pulmonary arterial hypertension (WHO Group 1)

• idiopathic
• heritable (no current gene therapies)
• drug and toxin induced (fen fen, methamphetamines including stimulant medications prescribed)
• connective tissue disease (scleroderma)
• HIV
• portal hypertension
• congenital heart disease
• Schistosomiasis (#1 cause of pulmonary hypertension outside the US)

A quick interruption to review the three types of CT chest you might consider to evaluate the lungs:

• CT angiogram (aka CTA) is a very quick scan from feet to head chasing the dye, itskips very low bases and apices of lungs and should never be used to assess for interstitial lung disease. Great for acute PE asessment.
• A High Resolution CT Chest: much thinner cuts (2mm) than a CTA starting at apices and going all the way to the bases. 
• Very high detail of parenchyma
• Ground glass opacities can be atelectasis vs. ILD--> flip when prone to see if atelectasis resolves while doing high res scan
• CT w/wo contrast (e.g. nodule) 
• can see 4 generations of branches of bronchial tree, but keep in mind that there are 17, so you cannot see filling defects in the small peripheral vessels

Treatment of Pulmonary Arterial Hypertension (PAP)

1. First identify if the patient has any WHO 2-5 diagnoses that may be influencing their pHtn and treat them maximally, then repeat TTE to check for PAP
2. If they still display pHtn on TTE, they now meet criteria for pulmonary arterial hypertension (PAP).
3. Consider pulmonary vasodilator therapy (obviously in conjunction with pulmonologist). These, while still very expensive, are coming down in price. The meds range currently between $40,000 to $100,000 per year.

When to treat Pulmonary Arterial Hypertension?

There is NO specific number for pressure goals. Look at patients functional class, 6 minute walk, and Echo

Treatment goals:

• Functional class: symptoms at rest (class IV), normal (class I): goal is 2 or less
• 6 minute walk test: goal is 400mg in 6 minutes ("please walk as far as you can in 6 minutes", not "as fast as you can walk")
• BNP: can be elevated in R heart strain, goal is normal
• Echo: goal is RV not fat and chubby, decompressed and slender, TAPSE moving nicely

Pulmonary Hypertension Therapy

• Endothelin pathway: block (bosentan (black box liver toxicity, no longer used), ambrisentan, macicentan: side effects: edema, check LFTs, watch for rare malignant facial edema
• Nitric oxide pathway: enhance (sildenafil TID, tadalafil QD, no lab monitoring, can get blue green colorblindness, rare complication anterior ischemic optic neuropathy (sudden blindness one eye, reversible when stop), riociguat (TID, more systemic hypotension)
• Prostacyclin pathway: enhance (potent, short half life and unstable)
• epoprostenol: IV infusion, tubing connected to a pump, best mortality data, very labor intensive
• treprostinil: IV vs. sq (like insulin pump) and inhaled QID (takes a lot of time, breathing treatment like nebulizer, 20-30 minutes per treatment
• iloprost: inhaled 6-9 times/day
• selexipag: oral BID, no labs but unrealistic uptitration protocol

Guidelines for treatment are based on functional class. The ultimate goal is minimal symptoms with regular activity

If functional class IV-->  needs prostacyclins right away

If functional class III-->  can start with orals (e.g. tadalafil and macicentan)

Any questions? Email or staff message Dr. Helena Wang at: helena.wang@sutterhealth.org

Diabetes Medications for Cardiovascular, Heart Failure, and Renal Risk Reduction (Magnotti - 7/20/22)

 A recording of the presentation can be found HERE.

Cardiovascular Benefit of New Diabetes Medications (Magnotti, 4/22/2020)

One of the reasons I love Grand Rounds is that each week I know-- whatever the topic, whomever the speaker-- I will walk away wiser. My curiosity will have been piqued. I will have learned something. I will have been challenged.  I will be a better family physician. And I will have often have new (more educated) questions.

And as expected, this week, Dr. Mike Magnotti (SMGR Endocrinology) did not disappoint. He gave an excellent presentation on the cardiovascular benefits of two classes of "new" diabetic medications: GLP-1 analogs and SGLT-2 inhibitors. Definite practice changer for me.

Here are a few questions to start you off:

• Do you manage your diabetic patients with cardiovascular disease  (CVD) differently than those without CVD?
• Are you aware of the evidence that both the GLP-1 and SGLT2-inhibitors reduce stroke, MI and possibly even CV death in diabetics with CVD?
• Are you using GLP-1 agonists for cardiovascular benefit?  What about SGLT-2 inhibitors?
• How do you (and your patients) assess whether or not they should be on one of these new meds?

I don't know about you, but I have a hard time keeping these medications in my head-- the names are complicated, the abbreviations don't make it simpler, the mechanisms of action are new, and nothing sticks. Plus, until recently they have been unavailable to most of my patients due to cost and/or insurance restrictions.

In case you are in the same boat as me, here's a brief summary of the two classes of meds Dr. Magnotti presented evidence for in CV risk reduction:

GLP-1 agonists: glucagon-like peptide 1 agonists (aka incretin mimetics) are almost all INJECTABLE medications (except for one new oral version of semaglutide). They act on the gut: improve glucose-dependent insulin release, suppress glucagon, suppress hepatic glucose output, decrease the rate of gastric emptying, and suppress appetite.  

• Benefits of GLP-1 agonists include HbA1c reduction of 1.2-1.7%, weight loss, no risk of hypoglycemia (unless combined with insulin or sulfonylurea), and CV risk reduction  (non fatal heart attack and stroke-- see below for details)
• Side effects: mostly GI (nausea, vomiting, constipation, diarrhea), headache, injection site reaction, possibly pancreatitis, and a black box warning MEN2 or medullary thyroid cancer
• Currently available forms: short and long acting exenatide, liraglutide, dulaglutide, semaglutide (oral and sq)

SGLT-2 inhibitors: sodium-glucose co-transporter-2 inhibitors (aka gliflozins) are ORAL medications that inhibit resorption of glucose into the kidneys, thereby lowering blood sugar

• Benefits of SGLT-2 inhibitors include: Hba1c reduction 0.8-1.2%, systolic BP reduction (~5mm Hg), weight loss (2-4% of body weight), heart failure risk reduction, slowed progression of CKD, CV risk reduction (non fatal heart attack and stroke-- see below for details), and even CVD death reduction (empagliflozin only)
• Side effects:  yeast infections (women>>men), UTI/pyelo, polyuria, transient decrease in GFR, orthostasis (esp in elderly), small increase in LDL, hypoglycemia (if combined with sulfonylurea, insulin), DKA with minimal glucose elevation, increase in fractures, possible increase in amputation, fournier's gangrene
• Currently available forms: canagliflozin, empagliflozin, dapagliflozin, ertugliflozin

Is HbA1c lowering the only outcome that matters?
Standard diabetes management has focused on reduction of HbA1c, which we know prevents progression of microvascular disease but has little effect on macrovascular outcomes. HbA1c goals are the metric by which we have considered a patient "controlled" or "uncontrolled". You all know, our  goal is HbA1c<7 in most adults, <8 in elderly and those with significant comorbidity.  Secondary goals have been to prevent/avoid hypoglycemia and prevent weight gain/promote weight loss.

It may be time to rework our paradigm; start thinking diabetes meds in CV Risk Reduction
Yes, we know lowering HbA1c is important to prevent retinopathy, diabetic nephropathy, peripheral neuropathy. However, we also know that cardiovascular disease (CVD) is an important cause of morbidity and mortality in diabetic patients. What if there were medications that reduce HbA1c and also reduce the risk of MI, stroke, and CV death?

Guess what? There are! Both the GLP-1 agonists and the SGLT-2 inhibitors seem to have a positive effect on CV outcomes (ie they reduce heart attack, stroke, and maybe even CV death). To be right up front, no one is exactly sure why.

Since 2008-- due to concern about thiazolidinidiones (TZD) actually showing increased CV risk in diabetic patients-- the FDA has required that any new blood sugar lowering med be evaluated for cardiovascular safety ("a cardiovascular outcome trial" or CVOT). Most of these studies use a composite endpoint called a 3 point MACE (time to a Major Adverse Cardiac Event, including non-fatal MI, CVA or cardiovascular death). Initial studies found most novel diabetes meds to be neutral, but  more recently, they started to show some benefit.

Here are the studies Dr. Magnotti reviewed during Grand Rounds:

• EMPA-REG: (empagliflozin), NEJM 2015
• DM2, a1c range 7-10%, BMI<45, established CVD--> primary outcome 3P MACE 
• Relative risk reduction of 38%, 2.2% Absolute risk reduction
• NNT 46 patients for 3.1 years to prevent on CV death (for comparison sake, NNT is 31 patients for simvastatin x5.4 years, 49 patients with ramipril x 5 years)
• There were also significant reductions in all-cause mortality and heart failure hospitalizations
• FDA indication for empagliflozin: to reduce risk of CV death in diabetic patients with known CVD
• CANVAS/CANVAS R (canagliflozin), Circulation 2018
• Primary outcome: 3P MACE
• Relative risk reduction 14%, NNT=224
• LEADER: (liraglutide), NEJM 2016
• Primary outcome: 3P MACE
• Relative risk reduction, 13%, 3P MACE
• Reduction in all cause mortality 15%, CV death 22%
• SUSTAIN 6 (semaglutide injection), NEJM 2016
• 26% relative risk reduction 3P MACE

Dr. Magnotti's summary of the literature: 

• To date, 5 new diabetes agents have been shown to lead to a significant reduction in 3 point MACE. 
• This effect is INDEPENDENT of A1c and other risk factors. 
• These were all measured in addition to other standard of care therapies (such as ASA and statin)

In light of these studies, both the American Diabetes Association (in 2018, again in 2020) and the American COllege of Cardiologists (ACC, 2020) have updated their guidelines with regards to using SGLT-2 and GLP1 medications in diabetes. 

For patients with known ASCVD, these medications should now considered first line after metformin (see diagrams below from ADA and ACC).

ADA guidelines HERE in FULL text (snippet of image).

ACC guidelines HERE in FULL text (snippet of image). 

In Type 2 patients with Diabetes AND CVD (ie. known CAD, hx MI, hx CVA, PVD), regardless of A1c or current diabetes therapy, patient should be started on EITHER GLP-1 (liraglutide daily injection, dulaglutide weekly injection, semaglutide weekly injection) OR SGTL-2 (empagiflozin oral, canagliflozin oral)

Dr. Magnotti's Considerations when choosing an SGLT2 vs. GLP-1

• SGTlL-2 in patients with Heart Failure, CKD (GFR>30), those who might need improved BP control (or who you aren't worried to be on a diuretic), someone with history of pancreatitis, gastroparesis, significant nausea, or MEN2/MTC
• GLP-1 in patients who need MORE Hba1c reduction, CKD with GFR<30, recurrent yeast infections or UTI, concern for risk of DKA or other potential side effects from SGLT-2

Some practicalities:

You don't need to adjust a patient's other diabetes meds UNLESS they are on insulin or sulfonylurea (for risk of hypoglycemia)

• IF they are on a sulfonylurea:
• A1C<7 to 7.5, stop the sulfonylurea
• A1C 7.5-8.5, cut sulfonylurea dose in half
• A1c >8, no change
• IF on basal insulin
• a1c<7, cut insulin dose in half
• a1c7-8, reduce insulin dose by 20%
• IF on prandial insulin, consider getting endocrinology input OR cut prandial insulin at least in HALF. 
• IF patient on antihypertensive, for SGLT2, consider reducing dose, if diuretic cut dose or stop

What about insurance coverage?

Coverage has substantially improved for these medications with CV indications. (Even with Partnership Health Plan). There are NO other medications that can be used for "step therapy" for CV risk reduction, so be sure to prescribe these under CVD (rather than DM). 

What about patients who don't want to take an injection?

If the patient meets criteria for a GLP-1 but doesn't want an injection, remind them: 1) this isn't insulin 2) they will likely LOSE weight and improve their blood sugar control and 3) they will reduce their risk of heart attack and stroke. Then get them nursing and diabetic educator assistance with getting over the injection!

If you work in the hospital, you might at least consider discharging every diabetic patient with established CVD (MI, CVA, TIA, PVD) on a GLP-1 or SGLT-2 agent. 

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Another reason I love Grand Rounds is that I love sitting in the same room with engaged, big-brained, big hearted colleagues. (This is the part I miss during our shelter in place-- Zoom works-- but it sure isn't the same). Join us next week on Zoom. We will be back in that conference room eventually.

ACS (Brenner 12/18/2019)

Thank you to Dr. Dan Brenner for his great talk this week on Acute Coronary Syndrome (ACS).

A dear mentor and teacher of mine who knows more than almost anyone I know said in the hallway after GR, “You know, you think you know everything there is to know about a topic, and then you go to Grand Rounds. . .and I learn something new every time!”

It’s true.

Here’s what I learned this week:

·         Family docs are the masters of prevention. (I already knew that!)

o   Diet and exercise modifications can reduce CAD risk up to 50%. Wow!

o   Use the ASVD calculator to guide primary prevention recommendations (not applicable to those with known CAD)

§  Patients with ASCVD 10 year risk >7.5% OR with Diabetes should be on a statin AND aspirin

§  Coronary calcium score may also help guide decisions about ASA for primary prevention

·         Stable Coronary Artery Disease should be managed medically

o   Ischemia Trial  of >5000 patients with stable CAD (excluded left main disease) raises questions about medical management vs. invasive treatment (PCI) in Stable CAD

§  Their bottom line: medical management trumps PCI, BUT I will note that Dr. Brenner took issue with some of their conclusions

·         Optimal medical therapy is CRITICAL in the treatment of stable disease, AND  revascularization may still be indicated in patients to prevent long-term risk of MI and improve symptoms (i.e. angina)

§  Shared decision-making should be employed (my favorite topic!!)

·         To review definitions in ACS

o   Unstable angina: chest pain, no EKG changes, no cardiac enzyme elevation

o   NSTE-ACS: chest pain, +/- EKG changes (e.g. non-specific, ST depressions, T wave inversions, etc), +cardiac enzyme elevation

o   STEMI: chest pain, ST elevation EKG changes, +/- cardiac enzyme elevation

·         The best thing a patient can do if they are having an MI is call 911. The ambulance can expedite an EKG and mobilize cardiology teams at the hospital because “time is myocardium”

o   Goal EMS to drug (heparin) <30 minutes

o   Goal EMS to balloon <90 minutes

o   Symptom onset to reperfusion <120 minutes

·         Pharmacotherapy: beta blocker (slow heart rate), nitrates, ACE-I, statin, dual antiplatelet (ASA+ ticagrelor, ASA+clopidogrel),

o   Goal: optimize balance of myocardial supply/demand

·         Percutaneous intervention (PCI)

o   Goal: open the artery, optimize balance of myocardial supply/demand

o   Radial approach is better than femoral (decreased risk bleeding complications)

o   After a drug eluting stent (DES) is placed, dual antiplatelet therapy (DAPT) should be continued for at least a year (call the cardiologist if you have questions).

o   Complications of PCI occur of 1-2% of patients: bleeding, contrast-induced neophropathy, Acute CVA/embolism, dissection/perforation, MI, emergent CT surgery, death

·         ACS secondary prevention (that is us again!)

o   Smoking cessation

o   Cardiac rehab (supervised exercise program)

o   Diet

o   Medical therapy: ASA +/- p2y12 inhibitor (ticagrelor, clopidogrel), statin, ACE-I (improved survival), aldosterone antagonist (reduced HF and sudden cardiac death), beta blockers (reduced HF, infarct size, arrhythmia, sudden cardiac death)