Dec 20, 2019
In this Live Friday CME Series recap, Dr. Todd Holcomb, an Internist and hospitalist with Lakeview Clinic and Ridgeview Medical Center, presents an interesting Internal Medicine case that is sure to scratch some heads, and remind us of the need to go back to the beginning, if it's not making sense after several attempts. Dr. Holcomb is accompanied by cardiologist Dr. Joshua Buckler, with Minneapolis Heart Institute, Dr. Jonathan Larson, family physician at Lakeview Clinic, Dr. Carl Dean, nephrologist with Kidney Specialists of Minnesota, and Dr. David Gross, radiologist with Consulting Radiologists.
So put on your thinking caps, listen closely and ask yourself what you would do as Dr. Holcomb guides us through this interesting case.
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Alright, let's break down the first portion of this case discussion. This is a 60 yo male with chest pain for over a year. Intermittent aching and burning in right anterior chest, worse with activity and lately has worsened overall with a stressful job and strong family hx of heart disease. General exam ins unremarkable. ECG normal. HDL is 60 and LDL slightly up at 137. PFTs and CXR are normal. Stress echo is normal. Cardiology referral results in a low Ca++ score but some plaque in the LAD.
Dr. Buckler, the cardiologist, feels this is ischemic heart disease until proven otherwise. Therefore, a coronary angiogram is necessary. Imaging has its limitations, as do stress tests. When the history still doesn't point in another explicable direction, we must follow the logic and most likely etiology, which is till coronary artery disease and ACS. One of the problems with stress tests in general, is there are limitations inherent. It's hard to miss the big stuff, but the more minor findings can be missed. With a high pretest probability, he could have perhaps gone straight to angio. In this case, though, he was started on a statin and aspirin. Per Dr. Buckler, Imdur could also have been given.
Two year later, he comes in with headaches in the same area of the head since his wife recently passed away. He takes Advil for this. BP has been elevated at home. Dr. Jonathan Larson, family physician, questions the type of headache, it's location and possible etiologies. Is the Advil causing rebound headaches or contributing to the headaches? The elevated home blood pressures also need further investigation. His kidney function is temporarily normal. NSAIDs are d/c'd and Lisinopril is started.
A month later, the headaches have improved. BP improved, but not tremendously. In addition, his chest pain has gone away. A new antihypertensive, a combo HCTZ/Lisinopril regimen is started. Although Amlodipine would have been a reasonable choice.
A year later, he returns with the same chest pain on exertion. Normal ECG. Normal renal function too. He now goes back to a CT angiogram showing multi-vessel disease. Per Dr. Buckler, one of the reasons he has worsened on a statin is that we may have limited understanding of his pathology, or potentially the CTA was not accurate the first time. Virtual FFT now can show the flow and how significant the lesion is, which is an advancement in this technology. Unfortunately, despite aggressive lipid therapy, sometimes people progress. A few days after the CTA, his Creatinine goes up a bit and GFR goes to 43. This is also after years of Lisinopril. Dr. Carl Dean comments on this alteration in renal function. He feels this is not entirely unexpected, but the data doesn't really reflect CIN (contrast induced nephropathy). Yet intuitively and experientially, we sometimes see this. The amount of contrast used is significantly more on a CTA than on an invasive angio.
At this point, the ACE inhibitor is held and Amlodipine is started. Renal function now has improved.
The angiogram demonstrates significant 3 vessel disease, with good downstream targets. The SYNTAX surgical risk score directs the cardiologist toward CABG instead of PCI.
Post angio, he develops some lower extremity edema, and he is discontinues on Amlodipine, resumed on the HCTZ, Lisinopril. The creatinine is now 2.4. Did he receive enough fluids for the angiogram? Or was the few hundred cc's he obtained during the angio okay? Again, hindsight is 20/20, but the data doesn't support a causality for AKI due to CIN, nor is there a true preventable measure, including n-acetylcysteine or bicarbonate. Perhaps, in this case, CIN as a possibility in the past as discussed, that many would not argue with overhydrating. Ultimately it was felt the ACE and contrast contributed to his creatinine elevation. The ACE combo is now stopped and he is started on Hydralazine and Metoprolol.
Creatinine improves, and he goes into CABG surgery. He is discharged and he continues on aspirin and Plavix for 3 months, and Carvedilol and Hydralazine. Atorvastatin is increased to 80 mg daily, a more aggressive dose. EF is normal on echo.
Do statins affect kidney function positively or negatively? According to Dr. Dean, there is no trial that supports either. His BP starts to increase, and Lisinopril is once again added, along with an increase of creatinine, and the ACE is again d/c'd. HCTZ was added. Then spironolactone for ongoing HTN. He's still running high though. Labetalol is replacing carvedilol now. And the pressure is still running high. What is happening here? What to do next? Do we try Lisinopril again? It is attempted, and he once again fails the creatinine test. It goes up again.
What we do now for this patient? It seems he can only improve on Lisinopril for blood pressure, but his creatinine continues to go up. According to Dr. Dean, in this patient, Lisinopril may not be a great option going forward, not only due to creatinine increase, but it will not help him in terms of mortality outcome. renal artery stenosis is a concern in this case. Dr. Tara McMichael interjects the question, could a loop diuretic have been tried? With a creatinine of 2.3, a loop diuretic could have been an option, since volume and sodium retention could be contributing to the hypertension. Isosorbide with hydralazine is also an option if more meds were to be added. Per Dr. Buckler, however, a four drug regimen that is poorly controlling blood pressure doesn't necessarily indicate adding a fifth drug. We need to know if there is a secondary cause of HTN. Sometimes, even in the setting of renal artery stenosis, patients still require significant anti-HTN drug regimens. Also, per Dr. Dean, the pretest probability in this type of patient for renal artery disease is high. And will an intervention be desirable if it is found? The ASTRAL trial demonstrated no improvement in outcomes. The CORAL trial was also done and considered to be a negative trial. One of the trial criticisms though was that it didn't include patients with severe enough disease. According to Dr. Dean, refractory hypertension should cause screening for this and an intervention should be done if it is seen. Our patient has a renal u/s that shows bilateral RAS.
Dr. David Gross, radiologist discussed the results of the MRA. The aorta, SMA and celiac trunk show atherosclerosis. The renal arteries are paired bilaterally. They have moderate to high grade narrowing of the arteries. Dr. Buckler asks the question of the safety of gadolinium in renal disease. In the setting of low GFR, in other words, less than 30, the risk for nephrogenic systemic fibrosis exists, although very rare. This is usually fatal, though. Basically, he has 4 out of 4 arteries occluded. Dr. Dean feels referral to a center of excellence for this unique issue is best for the patient. He undergoes transaortic endarterectomy, as his creatinine is rapidly going up. A significant plaque is resected from the aorta which was extending into the renal arteries. Post-procedure, he is placed on metoprolol, requiring nothing further. Rosuvastatin, Zetia and baby aspirin is started. Basically, unclogging the pipes resulted in a cure. And a while later, he's no longer on any antihypertensives. Blood pressures are great now. LDL now 57 on the new cholesterol meds. Zetia has limited data, but the PcsK9 inhibitor and his LDL is now 1. Dr. Buckler states there is a lot of unknowns about the LDL levels and whether there is a point of diminishing returns, but the science is not there yet. In this case, Dr. Buckler feels that stopping the Zetia and continuing the pcksk9 inhibitor makes sense.
Renovascular HTN is more commonly found in the setting of acute, severe, refractory, very high blood pressure. Work-up is needed when there is a strong possibility of secondary cause, and in the absence of another secondary cause, like pheochromocytoma or hyperaldosteronism. Also in an acute rise in BP, a young age, elevated Cr after starting an ace inhibitor, etc. Renal asymmetry on imaging and flash pulmonary edema are other clues. If Cr and BP are stable in the setting of stenosis, no intervention is indicated. Testing can potentially worsen function, as can the interventions performed to treat the disease. Who benefits most? People with short term hx of HTN, people who fail optimal medical therapy, not tolerating medical therapy and progressive renal failure. Ultrasound and CTA or MRA are the options for work-up. US is cheaper, but time consuming and operator dependent, with modest sensitivity/specificity. CTA is accurate for atherosclerosis. Highly sensitive and better if GFR below 30. MRA is highly sens/spec. Gadolinium complications can ensue in low GFR situations. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9) will lower LDL up to 60%. 50% decease in stroke and MI risk. The PCSK9 enzyme binds to liver LDL receptors and thereby increases plasma LDL levels. so inhibiting this enzyme leads to a lower LDL level. These inhibitors also can decrease triglycerides, increase HDL somewhat and decrease the volume of atheroma. Low adverse effects are noted with the med as well.
Regarding renovascular HTN, Dr. Dean also reminds us that someone who is significantly older with chronic renal ischemia in the setting of this disease, may not have improvement in renal function even after intervention. Therefore, some of these patients who suddenly reperfuse a chronically ischemic kidney may actually worsen. Renal artery stenosis is also not an absolute contraindication for ACE. Such as in low EF heart failure. If the creatinine markedly rises, it can be discontinued again. Fibromuscular dysplasia patients, unlike atherosclerosis patients, should all receive an intervention. This is more commonly found in younger patients.
Dr. Buckler addresses the ease of use and cost of the PCSK9 inhibitors. It turns out the cost is high at this point, up to $14k/year. But coverage has shown promise in FH and refractory high LDL.
As it was alluded to by Dr. Holcomb, the patient really doesn't exercise and has a very stressful job, as it turns out. His dies wasn't discussed. Was he managing his risk factors very well? What does that mean nowadays? We have potent medications and skillful intervention options for reacting to this sort of pathology nowadays, but where are we at with prevention? Hopefully a conversation for another day.