By Peter Laird, MD
Dialysis induced myocardial ischemia (myocardial ischemia is the condition where the blood supply is inadequate for the heart's oxygen demand. Typically this can lead to symptoms of angina, but during hemodialysis it seems to be silent i.e. without symptoms) is found in the majority of patients tested in several small cohort studies to date, as well as the secondary sequelae of myocardial stunning and hybernation. Of note is that the patients selected in this study, Haemodialysis is associated with a pronounced fall in myocardial perfusion, had no clinical evidence of coronary artery disease but this was not confirmed with coronary angiogram.
This article is of interest because the historical risk of sudden cardiac death is greater in dialysis patients than myocardial infarction, so even though small and lacking confirmatory data, the results of the paper present an intriguing postulate of what is the cause of this ubiquitous phenomenon of myocardial ischemia.
Several complex factors leading to myocardial fibrosis may create an intrinsic cardiac substrate in dialysis patients, perhaps dating from the earlier CKD stages, increasing their susceptibility to external hemodynamic stressors as well as complex fluid and electrolyte balances. Higher than normally recommend blood pressure reduces the risk of death in hemodialysis patients which is a paradoxical finding to the general population. However, in light of the prevalent myocardial ischemia during dialysis sessions, this makes intuitive sense since the coronary arteries are the only arteries in the body that fill during diastole when the heart muscle relaxes and not during systole when the heart muscle contracts. A higher mean arterial pressure translates into higher perfusion pressures in the coronary arteries. This may be a protective mechanism against myocardial ischemia that is not present in patients with lower average blood pressures.
Another interesting datum is that cooling of the dialysate from the standard 37C to 35 C has been shown to reduce regional wall motion abnormalities and heart arrhythmias during dialysis. How this happens is understood reasonably well. Reducing the dialysate temperature promotes vascular reflexes in the extremities constricting those blood vessels which secondarily raises the mean arterial blood pressures. It is quite possible that the beneficial effects of cooling the dialysate is directly related to the beneficial effects of higher than normal blood pressures as well. Dialysis-Induced Regional Left Ventricular Dysfunction Is Ameliorated by Cooling the Dialysate:
Forty-nine new RWMA developed in nine patients during hemodialysis with dialysate at 37°C (HD37), compared with thirteen [Regional Wall Motion Abnormalities] RWMA that developed in four patients during [dialysate at 35°C] HD35 (odds ratio 3.8; 95% confidence interval 2.1 to 6.9). The majority of RWMA displayed improved function by 30 min after dialysis. Overall, regional systolic LV function was significantly more impaired during HD37 (P < 0.001). BP was higher during HD35, with fewer episodes of hypotension as a result of a higher peripheral resistance and no difference in stroke volume.
A recent article by Kidney Disease: Improving Global Outcomes (KDIGO) on blood pressure controversies offers a unique clue to a possible contributor to an increased risk of sudden cardiac death: Blood pressure in chronic kidney disease stage 5D—report from a Kidney Disease: Improving Global Outcomes controversies conference (PDF link):
Cardiac deaths account for the majority of CV deaths in dialysis patients. The exact etiologies of these cardiac deaths are often unknown and likely include primary and secondary arrhythmias, cardiomyopathy, and coronary artery disease, and involve complex pathogeneses. Although fluid overload, increased afterload from HTN and vascular calcification, calcified valvular disease, and ischemia are probably important contributory factors, uremia per se seems to be an additional factor. To what extent hyperkalemia and hypokalemia, frequently present in these patients, contribute to the high incidence of sudden death in dialysis patients is not certain, but recent papers suggested the greater danger of hypokalemia.
Hypokalemia not only increases the risk of cardiac arrhythmias, it can also directly impair skeletal muscle contraction and contribute to vascular constriction through its action on vascular smooth muscle.
Low potassium baths correlate directly with an increased risk of cardiac arrhythmias that can be attenuated by potassium profiling. The issue that has not been clarified is whether rapid removal of potassium with low K baths could produce vascular constriction and ischemia to not only the heart but other vascular beds such as the cerebral and mesenteric. Hypokalemia (a lower-than-normal amount of potassium in the blood) experimentally produced in dogs can cause such severe vascular constriction that rhabdomyolysis occurs. Is it possible that the near universal myocardial ischemia seen in conventional hemodialysis patients is a combination of myocardial fibrosis which predisposes dialysis patients to hemodynamic and electrolyte shifts seen in dialysis, combined with severe and progressive vascular constriction as the potassium levels progressively fall during a dialysis session?
There is no direct evidence that hypokalemia is the cause of myocardial ischemia in dialysis patients, but the confluence of progressive arrhythmias with lower levels of potassium in the dialysate and hypokalemia causing severe vascular constriction capable of cerebral ischemia and rhabdomyolysis is a potentially actionable etiology if present. I believe it is time to return to basic laboratory studies with animal models to test the effects of potassium concentrates during dialysis looking specifically for myocardial ischemia.
My review of papers since the ADC suggests there is telling, though indirect, evidence to implicate a component intrinsic to high speed conventional dialysis as causing myocardial ischemia universally in conventional hemodialysis patients. This initial insult then causes a cascade of problems leading to LVH, and CHF and is also associated with sudden cardiac death. It is a progressive finding that appears to worsen during the course of dialysis in a near linear manner, which does parallel the removal of potassium during conventional HD. Conversely potassium profiling has shown success in reducing episodes of ventricular ectopy and other forms of cardiac arrhythmias, which are markers of a higher risk of sudden cardiac death.
The vasoconstrictive effects of hypokalemia require that this single factor have its day in court as it were. Research is needed now to tease out whether to include or exclude it as a putative cause. If we are looking for a single entity that can cause both arrhythmias and vascular constriction in the coronary arteries, then hypokalemia related to low potassium mixtures in dialysate is the most logical first place to look.
You're over my head with the physiology, Peter. But there's another piece of the puzzle: erectile dysfunction, which is staggeringly common among folks doing standard in-center HD, and which turns out to be a "strong predictor of fatal heart ailments" in a new study of folks NOT on dialysis... http://www.latimes.com/news/nation-and-world/la-sci-ed-heart16-2010mar16,0,6988279.story
Posted by: Dori Schatell | March 16, 2010 at 09:29 AM