Vasopressors independently associated with mortality in acute myocardial infarction and cardiogenic shock.

BACKGROUND: Increasing vasopressor dose is associated with increasing mortality in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS). It is unknown whether the use of vasopressors is independently harmful or if their use is secondary to decreasing intrinsic cardiac power output (CPO). Mechanical circulatory support (MCS) devices enhance CPO. We sought to evaluate the independent impact of increasing vasopressor dose on survival in the National Cardiogenic Shock Initiative (NCSI). METHODS: The NCSI is a single arm prospective trial evaluating outcomes associated with the use of MCS using Impella in patients with AMICS. Early initiation of MCS placement before percutaneous coronary intervention (PCI) and rapid de-escalation of vasopressors guided by systematic use of invasive hemodynamic measures led to 70% in-hospital survival for the first 300 patients enrolled from July 2016 to December 2019 in 57 U.S. sites. RESULTS: Hemodynamic measures were obtained immediately after MCS and PCI. Survival curves were constructed based on CPO and use of vasopressors. For patients with CPO ≤0.6 W, survival was 77.3%, 45.0%, and 35.3% when 0, 1, or ≥ 2 vasopressors were used (p = 0.02). Similarly, for patients with CPO >0.6 W survival was 81.7%, 72.6%, and 56.8%, respectively (p = 0.01). Logistic regression analysis demonstrated that increasing vasopressor requirements were independently associated with increasing mortality (p = 0.02). CONCLUSION: Increasing vasopressor requirement is associated with increased mortality in AMICS independent of underlying CPO. Methods to decrease the need for vasopressors may enhance survival in AMICS.

Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative.

BACKGROUND: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI). METHODS: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS. Inclusion and exclusion criteria mimicked those of the "SHOCK" trial with an additional exclusion criteria of intra-aortic balloon pump counter-pulsation prior to MCS. RESULTS: A total of 171 consecutive patients were enrolled. Patients had an average age of 63 years, 77% were male, and 68% were admitted with AMICS. About 83% of patients were on vasopressors or inotropes, 20% had a witnessed out of hospital cardiac arrest, 29% had in-hospital cardiac arrest, and 10% were under active cardiopulmonary resuscitation during MCS implantation. In accordance with the protocol, 74% of patients had MCS implanted prior to PCI. Right heart catheterization was performed in 92%. About 78% of patients presented with ST-elevation myocardial infarction with average door to support times of 85 ± 63 min and door to balloon times of 87 ± 58 min. Survival to discharge was 72%. Creatinine ≥2, lactate >4, cardiac power output (CPO) <0.6 W, and age ≥ 70 years were predictors of mortality. Lactate and CPO measurements at 12-24 hr reliably predicted overall mortality postindex procedure. CONCLUSION: In contemporary practice, use of a shock protocol emphasizing best practices is associated with improved outcomes.

Impact of Age in Acute Myocardial Infarction Cardiogenic Shock: Insights From the National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMICS) is associated with high mortality. Patients ≥75 years old represent an increasing proportion of those who present with AMICS and are at high risk for adverse outcomes. METHODS: The National Cardiogenic Shock Initiative includes patients with AMICS treated using a standard shock protocol with early invasive hemodynamic monitoring, mechanical circulatory support (MCS), and percutaneous coronary intervention (PCI). We evaluated the outcomes of patients based on their age group, dividing them into <75 and ≥75 years old. RESULTS: We included 300 consecutive patients: 238 were <75 years old (79.3%) and 62 patients ≥75 years old. There were significant differences in survival; patients <75 years old had a 75.6% survival, while those ≥75 years old had a 50% survival (adjusted OR: 10.4, P = 0.001). SCAI shock classification impacted survival as well; those <75 years old with class C or D shock had a survival of 84%, compared with 57% in those ≥75 years old. Patients ≥75 years old requiring 1 or 2 vasopressors had significantly lower survival rates (36% and 25%, respectively) when compared with patients <75 years old (76.7% with 1 and 60.5% with >1 vasopressor). CONCLUSIONS: Age is inversely proportional to survival; patients <75 years old have high rates of survival if treated using best practices with invasive hemodynamic monitoring, early MCS, and PCI. However, using a standardized protocol can improve survival in the elderly; therefore, age on its own should not be a reason to withhold PCI or MCS use.

Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis.

BACKGROUND: Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis. METHODS: We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR). RESULTS: Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in APOA5, APOC2, CETP, LPL and LIPC (each q

Optimizing the use of thrombolytics in ST-segment elevation myocardial infarction.

The advent of thrombolytic therapy was a major advance in the treatment of ST-segment elevation myocardial infarction (STEMI). The administration of fibrinolytic reperfusion therapy can reduce mortality rates by as much as 30%, with the greatest benefit observed if therapy is administered soon after symptom onset. Outcomes with thrombolytic therapy are improved if there is adjunctive treatment with aspirin, clopidogrel and an anti-thrombin agent. Although there is evidence that primary percutaneous coronary intervention (PCI) is the most effective reperfusion strategy, the majority of hospitals still do not have PCI capabilities and, thus, thrombolytic therapy remains a cornerstone of treatment for STEMI. Trials of thrombolytic therapy have demonstrated that initial patency rates can approach 85%, but there is still a need for improvement of non-invasive markers that predict failure or re-occlusion of the infarct-related artery. Because of the overwhelming data demonstrating the importance of rapid reperfusion, current studies are examining the role of earlier treatment of patients with STEMI via pre-hospital administration and/or coordinated systems for rapid diagnosis, transfer and delivery of definitive care. Facilitated PCI, a strategy of thrombolytic therapy followed by immediate PCI, has not been shown to be beneficial and current studies are examining the optimal timing of coronary angiography after thrombolytic therapy.

Optimal low-density lipoprotein levels: evidence from epidemiology and clinical trials.

Aggressive lipid lowering was initially controversial due to evidence from epidemiologic studies that implied an increase in total mortality with low cholesterol levels combined with equivocal results from early trials utilizing bile acid resins or fibric acid derivatives. The advent of statin therapy allowed significant reductions of circulating lipid levels and clearly reduced cardiovascular morbidity and mortality. Additionally, in adequately powered trials, total mortality was also reduced. The optimal level of circulating low-density lipoprotein (LDL) has not been definitely established. However, recent clinical trials with aggressive lipid goals have established that LDL cholesterol can be significantly lowered below 100 mg/dL with improvement in both surrogate measurements and hard clinical endpoints. Ongoing clinical trials have been initiated that will determine the optimal level of LDL cholesterol that will insure cardiovascular benefits and establish the risk-benefit relationship of aggressive pharmacologic lowering of circulating lipid levels.