Faculty Bibliography

OBJECTIVES: Guidelines recommend beta-blockers and renin-angiotensin-aldosterone system blockers to improve long-term survival in hemodynamically stable myocardial infarction patients with a reduced left ventricular ejection fraction. The prevalence and outcomes associated with beta and renin-angiotensin-aldosterone system blocker therapy in patients with ongoing cardiogenic shock is unknown. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: In patients with cardiogenic shock lasting more than 24 hours enrolled in Tilarginine Acetate Injection in a Randomized International Study in Unstable Myocardial Infarction Patients With Cardiogenic Shock, we compared 30-day mortality in patients who received beta or renin-angiotensin-aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists) within 24 hours of randomization with those who did not. INTERVENTIONS: None. PATIENTS: The final study population included 240 patients. A total of 66 patients (27.5%) had either beta blocker or renin-angiotensin-aldosterone system blocker administered within the first 24 hours after the diagnosis of cardiogenic shock. beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone antagonists were prescribed in 18.8%, 10.6%, and 5.0% of patients, respectively. MEASUREMENTS AND MAIN RESULTS: The observed 30-day mortality among patients was higher in patients who received beta or renin-angiotensin-aldosterone system blockers prior to cardiogenic shock resolution (27.3% vs 16.9%; adjusted hazard ratio, 2.36; 95% CI, 1.06-5.23; p = 0.035). Compared with patients not given beta or renin-angiotensin-aldosterone system blockers, the 30-day mortality was higher among patients treated only with beta-blockers (33.3% vs 16.9%, p = 0.017) but not among those only treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (18.2% vs 16.9%, p = 1.000). CONCLUSIONS: The administration of beta or renin-angiotensin-aldosterone system blockers is common in North America and Europe in patients with myocardial infarction and cardiogenic shock prior to cardiogenic shock resolution. This therapeutic practice was independently associated with higher 30-day mortality, although a statistically significant difference was only observed in the subgroup of patients administered beta-blockers.

There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.

Takotsubo cardiomyopathy is an acute reversible cardiac dysfunction syndrome associated with high circulating catecholamine levels. Our objective was to investigate whether abnormal cardiovascular control might play a role in the pathophysiology. We studied autonomic cardiovascular reflexes in 10 women who had takotsubo (33+/-7 months after being hospitalized) and 10 age/BMI matched healthy women. In the women with takotsubo, indices of vagal modulation of heart rate induced by respiration were uniformly reduced (expiratory:inspiratory ratio: p<0.01, pnn50%: p<0.02, rMSSD: p<0.03). Cognitive (stroop test: p<0.03) and emotional arousal (event recall: p<0.05) produced exaggerated pressor responses, without detectable ECG changes. Pressor responses to hemodynamic stimuli were also amplified (Valsalva SBP overshoot: p<0.05). Takotsubo women had increased BP variability in the short-term (St. Dev. SBP: p<0.01). Ambulatory recordings captured an exaggerated morning surge in SBP after awakening from sleep (p<0.05). Cardiovagal baroreflex gain was significantly lower in the takotsubo women (sequence analysis: p<0.01, regression method: p<0.001, transfer function gain: p<0.001). Women with takotsubo have heightened sympathetic responsiveness, labile BP and reduced vagal modulation of the heart. This shift in sympathovagal balance could play a role in the pathophysiology

PURPOSE OF REVIEW: A substantial minority of myocardial infarction (MI) patients have no obstructive coronary artery disease (CAD) at angiography. Women more commonly have this type of MI, but both sexes are affected. This is not an innocuous problem. Multiple studies have shown 2% death or reinfarction in short-term to mid-term follow-up. RECENT FINDINGS: Two large autopsy series confirmed MI without obstructive CAD as a cause of death. Intravascular ultrasound (IVUS) and cardiac MRI (CMR) were studied in patients with MI without obstructive CAD. Plaque rupture was found in nearly 40% and late gadolinium enhancement was seen in nearly 40%, with little overlap in imaging findings. Additional CMR studies in similar patients have shown variable frequencies and patterns of late enhancement, but consistently demonstrate an ability to identify nonischemic causes (myocarditis, infiltrative disease). Ischemic myocardial injury on CMR may be due to plaque rupture but also occurs in patients without plaque rupture. These cases may be caused by vasospasm, embolism, dissection, or branch occlusion. SUMMARY: MI without obstructive CAD is a heterogeneous disorder with different mechanisms in different patients. Plaque rupture is common. In the absence of clear demonstration of a nonischemic cause, treatment should include guideline-recommended secondary prevention, including antiplatelet and antiatherosclerotic medications.

BACKGROUND: The incidence and predictors of heart failure (HF) after myocardial infarction (MI) with modern post-MI treatment have not been well characterized. METHODS AND RESULTS: A total of 2,201 stable patients with persistent infarct-related artery occlusion >24 hours after MI with left ventricular ejection fraction <50% and/or proximal coronary artery occlusion were randomized to percutaneous intervention plus optimal medical therapy (PCI) or optimal medical therapy (MED) alone. Centrally adjudicated HF hospitalizations for New York Heart Association (NYHA) III/IV HF and mortality were determined in patients with and without baseline HF, defined as a history of HF, Killip Class >I at index MI, rales, S3 gallop, NYHA II at randomization, or NYHA >I before index MI. Long-term follow-up data were used to determine 7-year life-table estimated event rates and hazard ratios. There were 150 adjudicated HF hospitalizations during a mean follow-up of 6 years with no difference between the randomized groups (7.4% PCI vs. 7.5% MED, P = .97). Adjudicated HF hospitalization was associated with subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21-4.92, P < .001). Baseline HF (present in 32% of patients) increased the risk of adjudicated HF hospitalization (13.6% vs. 4.7%, HR 3.43, 99% CI 2.23-5.26, P < .001) and death (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71-3.10, P < .001). CONCLUSIONS: In the overall Occluded Artery Trial (OAT) population, adjudicated HF hospitalizations occurred in 7.5% of subjects and were associated with increased risk of subsequent death. Baseline or prior HF was common in the OAT population and was associated with increased risk of hospitalization and death.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels 90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.