Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction.

BACKGROUND: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear. OBJECTIVES: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI. METHODS: Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models. RESULTS: Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (ß = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury. CONCLUSIONS: The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).

Factors affecting thrombolysis in myocardial infarction myocardial perfusion frame count: insights of myocardial tissue-level reperfusion from a novel index for assessing myocardial perfusion.

BACKGROUND: Myocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown. METHODS: A total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC. RESULTS: STEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021). CONCLUSIONS: STEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.

Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction.

OBJECTIVE: The impact of gender on clinical course after ST-elevation myocardial infarction (STEMI) is not fully understood. We prospectively investigated whether there are gender-related differences in epicardial and myocardial tissue-level perfusion, both of which represent important prognostic determinants in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: A total of 594 consecutive non-selected STEMI patients undergoing PPCI were prospectively enrolled. Primary end-point of the study was post-procedural epicardial and myocardial perfusion. Secondary end-points were the 30-day and 6-month composite occurrence of major adverse cardiac events (MACE). RESULTS: Women with STEMI had higher risk factor profiles than men. Although PPCI achieved equal rates of successful epicardial reperfusion, women tended to have impaired microvascular reperfusion as reflected by lower rates of normal TIMI myocardial perfusion grade (P=0.007) and complete ST-segment resolution (P=0.079). After adjustment for the risk profiles, multivariable analysis showed that gender itself was not an independent predictor of impaired microvascular reperfusion. Both female gender and impaired myocardial reperfusion were independent predictors of 30-day MACE, whereas gender lost its prognostic significance for 6-month MACE. Multivariable analysis restricted to female patients identified incomplete ST-segment resolution as the strongest determinant of 30-day MACE. CONCLUSION: The differences in microvascular reperfusion after PPCI between women and men are attributed to higher risk profiles in women. Both female gender and impaired myocardial reperfusion were independent predictors of 30-day outcomes after PPCI, emphasizing the importance of successful microvascular reperfusion in the women with STEMI.

Comparison of epicardial and myocardial perfusions after primary coronary angioplasty for ST-elevation myocardial infarction in patients under and over 75 years of age.

BACKGROUND AND AIMS: Patients aged ≥75 years compose a high-risk subgroup for acute myocardial infarction (AMI). It is unknown whether myocardial perfusion in these patients is decreased compared with younger ones after primary percutaneous coronary intervention (PPCI), which may contribute to their worse prognosis. We compared epicardial and myocardial perfusions as well as short-term outcomes between elderly and younger patients undergoing PPCI. METHODS: A total of 547 consecutive PPCI patients were prospectively enrolled; of these, 106 were elderly (≥75 yrs). Epicardial perfusion was evaluated by the Thrombolysis in Myocardial Infarction (TIMI) flow grade and corrected TIMI frame count (CTFC), and myocardial perfusion was evaluated by the TIMI myocardial perfusion grade (TMPG) and ST-segment resolution (STR). RESULTS: Despite comparable epicardial perfusion pre- and post-PPCI, elderly patients had impaired myocardial perfusion after PPCI, as measured by reduced TMPG (35.9% vs 14.5%, p=0.001) and absent STR (18.9% vs 9.8%, p=0.009). After adjusting for clinical and angiographic risk profiles, multivariate analysis showed that age ≥75 years remained independently associated with reduced TMPG or absent STR. In the whole population, multivariate analysis revealed that both age ≥75 years and absent STR were independently associated with 3-month major adverse cardiac events (MACE). In the elderly subgroup, multivariate analysis identified absent STR as the strongest determinant of 3-month MACE. CONCLUSIONS: Age is associated with impaired myocardial perfusion, but not epicardial perfusion, after PPCI for AMI. To further improve the outcome of elderly AMI patients, efforts should be aimed at improving myocardial perfusion beyond epicardial recanalization.