Higher BP May Limit Myocardial Injury in AMICS
In a surprise finding, escalating inotropes and vasopressors was linked to lower hs-cTnT but not to harm.
Setting a more ambitious target for mean arterial pressure (MAP) through pharmacologic support in patients with acute MI complicated by cardiogenic shock (AMICS) appears to safely reduce myocardial injury, suggests a post hoc analysis of data from the Neuroprotect and COMACARE randomized trials.
Patients who reached around 80/85 to 100 mm Hg with more inotropes and vasopressors during the first 36 hours of their intensive care unit stay had lower values of high-sensitivity cardiac troponin T (hs-cTnT) over 72 hours compared with those treated with the typical goal of 65 mm Hg.
Koen Ameloot, MD (Ziekenhuis Oost-Limburg, Genk, Belgium), who led the study along with Pekka Jakkula, MD, PhD (Helsinki University Hospital, Finland), told TCTMD that the results came as a surprise to him. Originally, when conducting the Neuroprotect trial, Ameloot and colleagues had sought to see whether increasing cerebral perfusion through a higher MAP target could decrease anoxic brain damage. They feared, though, that one consequence of this strategy might be larger myocardial infarct size, as the heart was tasked with working harder.
“This was the reason why we decided to do close monitoring of troponins in the study protocol. . . . To our surprise, we found actually it was the other way around: improving blood pressure actually decreased myocardial infarct size,” Ameloot recalled. After hearing that the COMACARE investigators also had the same unexpected benefit when putting greater emphasis on inotropes and vasopressors, they decided to dig deeper, he said. “This was so in contrast with our daily practice that we absolutely wanted to investigate it.”
Despite the troponin difference, they found that mortality and neurologic outcomes were similar for both targets. Even so, Ameloot said, “it pays off to do everything you can to limit infarct size, because we know from MRI studies that every 5% decrease in infarct size translates into a 20% decrease in event rates over 5 years.”
Higher MAP Equals Lower hs-cTnT
For their study, published online ahead of the August 18, 2020, issue of the Journal of the American College of Cardiology, the investigators combined patient-level data from Neuroprotect and COMACARE, which randomized participants to a MAP target of either 65 mm Hg or a goal of 80/85 to 100 mm Hg. Of the 235 patients in that data set, the 120 who’d experienced AMICS were the focus of the current analysis. Among them, 58 had been allocated to the higher MAP target.
Patients in the higher-target group, as would be expected, received larger doses of norepinephrine and dobutamine and reached a higher MAP level than those in the lower-target group (86 vs 72 mm Hg; P < 0.001). Just six patients received “bailout” mechanical circulatory support, which consisted of intra-aortic balloon pump or extracorporeal membrane oxygenation.
At this point it’s not strong enough to advocate [for] the world to change practice, but I think the signal in both trials is strong enough, at least for me, to change my practice. Koen Ameloot
Admission hemodynamics and angiographic findings were similar in the two groups. Moreover, all patients underwent immediate angiography and PCI. Yet those with the higher MAP target had a significantly lower area under the curve for 72-hour hs-cTnT (median 1.14 µg/L) than those with the lower target (median 2.31 µg/L; P = 0.04). There was no penalty to be paid in terms of new cardiac arrest or atrial fibrillation.
By 180 days, all-cause mortality was statistically similar for patients at the higher and lower targets (36% vs 40%), as was the proportion who had a Cerebral Performance Category score of 1 to 2 (64% vs 53%). The researchers note that “the major cause of death was post-anoxic encephalopathy with brain death or withdrawal of ICU support because of neurologic futility,” which together accounted for 70% of the 46 deaths.
The mechanism by which myocardial injury was suppressed isn’t known, they acknowledge, though they propose that it relates to a core area of necrotic cell death.
“In patients with a large AMI, the necrotic infarcted core is surrounded by a large edematous border zone that on average accounts for one-half of the total area at risk,” they explain. “Although it is incompletely understood how the border zone may be salvaged, immediate restoration of the cellular oxygen balance is paramount. Additional use of inotropes and vasopressors would theoretically increase afterload, contractility, heart rate, and stroke work resulting in an unfavorable increase of myocardial oxygen consumption.”
However, that wasn’t what they saw here, the researchers continue. “Although we did not measure coronary perfusion and cardiac metabolites, one may assume that the reduction of myocardial injury is the net result of an increased oxygen delivery that offsets increased oxygen consumption.” Raising diastolic BP “plausibly provides more driving pressure for coronary perfusion and may potentially also recruit microcollaterals,” they propose.
Ameloot acknowledged the drawbacks to the pooled analysis, many of which were noted in an accompanying editorial by Venu Menon, MD (Cleveland Clinic, OH). “At this point it’s not strong enough to advocate [for] the world to change practice, but I think the signal in both trials is strong enough, at least for me, to change my practice,” Ameloot said. Now, he aims for 85 mm Hg for 24 hours.
For him, the main takeaway for clinicians is clear: “When you have a patient in cardiogenic shock after a STEMI with a blood pressure of 65 mm Hg, you should consider boosting the blood pressure to improve the coronary perfusion to salvage the border zone, which is not yet irreversibly damaged. This is the core message of the paper.”
Menon, the editorialist, stresses that the potential benefit seen here is intriguing but inconclusive. He points to numerous adverse consequences that can occur when escalating vasopressors; these “include increasing oxygen demand and afterload, worsening and provocation of ischemia, arrhythmogenicity, and direct myocyte toxicity.” That there was no harm here is “reassuring,” he adds, “but is possibly due to the completeness of revascularization and as a consequence of ongoing hypothermia.”
The aforementioned risks “will concern many cardiologists. Perhaps future studies that use varying degrees of temporary mechanical support to modify MAP will shed further light on this area,” Menon suggests.
Ameloot said a study is being planned that will measure coronary perfusion and cardiac metabolism in a larger sample of patients, with the primary outcome to cardiac MRI results at 3 months. “It’s at a very preliminary stage at this point,” in part due to the challenges of obtaining informed consent in the AMICS setting, he said.
Ameloot K, Jakkula P, Hästbacka J, et al. Optimum blood pressure in patients with shock after acute myocardial infarction and cardiac arrest. J Am Coll Cardiol. 2020;76:812-824.
Menon V. Targeting mean arterial pressure to limit myocardial injury: novel finding or wild goose chase? J Am Coll Cardiol. 2020;76:825-827.
- Ameloot, Jakkula, and Menon report no relevant conflicts of interest.