Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the high-risk myocardial infarction database.

AIMS: Among patients with acute myocardial infarction (AMI) complicated by heart failure [HF; clinical HF or left ventricular (LV) systolic dysfunction], we explored the probability of subsequent non-fatal cardiovascular (CV) events and sudden cardiac death (SCD). METHODS AND RESULTS: The high-risk myocardial infarction (HRMI) database contains 28 771 patients with signs of HF or reduced LV ejection fraction (<40%) after AMI. We evaluated the temporal association between SCD with preceding non-fatal CV event [HF hospitalization, recurrent myocardial infarction (MI), or stroke]. Median follow-up was 1.9 years. Mean age was 65.0 ± 11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-years and for SCD was 3.1 per patient-years (40% of CV deaths). The incidence of SCD preceded by HF hospitalization was greater than SCD without preceding HF hospitalization (P < 0.05). However, overall, SCD was less likely to be preceded by a non-fatal CV event compared to other causes of death: 9.6% of SCD events were preceded by an MI (vs. 46.6% for non-sudden CV death); 17.0% of SCD events were preceded with an HF hospitalization (vs. 25.4% for non-sudden CV death); and 2.7% of SCD events were preceded by stroke (vs.12.9% for non-sudden CV death). CONCLUSION: Among patients with AMI complicated by HF, SCD, compared with other causes of death, was less likely to be preceded by a non-fatal CV event. As patients are less likely to have preceding non-fatal CV events to alert the healthcare team of a possible impending SCD event, additional strategies for risk stratification for SCD are needed.

Genetics of coronary artery disease: should they impact the choice of revascularization?

PURPOSE OF REVIEW: Patients with multivessel coronary artery disease (CAD) may undergo revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). This review will discuss the use of polygenic risk scores for risk-stratification of patients with multivessel CAD in order to guide the choice of revascularization. RECENT FINDINGS: A 57-single nucleotide polymorphism (SNP)-polygenic risk score can accurately risk-stratify patients with CAD and identify those who will receive greater benefit from statin therapy. The most recent genomic studies reveal 243 different SNPs are now significantly associated with CAD. Randomized clinical trials comparing PCI vs. CABG (FREEDOM, SYNTAX, NOBLE, EXCEL) have uncovered factors related to CAD severity (diabetes, SYNTAX score) are critical determinants of outcomes after revascularization. SUMMARY: There is a need to discover predictors of outcomes after PCI vs. CABG to improve clinical decision-making in multivessel CAD. High polygenic risk score is associated with increased CAD severity and better outcomes with statin therapy. Randomized clinical trials indicate CAD severity is associated with better outcomes after CABG compared with PCI. Accordingly, polygenic risk score could also be associated with better outcomes after CABG vs. PCI and used to optimize revascularization for patients with multivessel CAD.

The aortic root does not dilate over time after replacement of the aortic valve and ascending aorta in patients with bicuspid or tricuspid aortic valves.

OBJECTIVE: Whether the aortopathy associated with bicuspid aortic valve (BAV) disease occurs secondary to genetic or hemodynamic factors remains controversial. In this article we describe the natural history of the aortic root in patients with bicuspid versus tricuspid aortic valves (TAVs) after replacement of the aortic valve and ascending aorta. METHODS: From 1990 to 2010, 406 patients (269 BAV, 137 TAV) underwent aortic valve and ascending aorta replacement at a single institution. Patients with aortic dissection, endocarditis, previous aortic surgery, or Marfan syndrome were excluded. All available follow-up imaging was reviewed. RESULTS: Mean imaging follow-up was 5.5 (±5.3) years. Of all patients, 66.5% had at least 1 aortic root measurement after the index operation. Baseline aortic diameter was comparable between groups. In patients with BAV, aortic root diameter increased at a clinically negligible rate over time (0.654 mm per year; 95% confidence interval, 0.291-1.016; P < .001), similar to patients with TAV (P = .92). Mean clinical follow-up was 8.1 (±5.4) years. During follow-up, 18 patients underwent reoperation, 89% for a degenerated bioprosthetic aortic valve. Only 1 patient underwent reoperation for a primary indication of aortic aneurysmal disease, 22 years after the index operation. There were no differences in cumulative incidence rates of aortic reoperation (P = .14) between patients with BAV and TAV. CONCLUSIONS: Mid-term imaging after aortic valve and ascending aorta replacement indicates that if the aortic root is not dilated at the time of surgery, the risk of enlargement over time is minimal, negating the need for prophylactic root replacement in patients with BAV or TAV.

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes.

Diabetes strongly associates with microvascular complications that ultimately promote multiorgan failure. Altered myogenic responsiveness compromises tissue perfusion, aggravates hypertension, and sets the stage for later permanent structural changes to the microcirculation. We demonstrate that skeletal muscle resistance arteries isolated from patients with diabetes have augmented myogenic tone, despite reasonable blood glucose control. To understand the mechanisms, we titrated a standard diabetes mouse model (high-fat diet plus streptozotocin [HFD/STZ]) to induce a mild increase in blood glucose levels. HFD/STZ treatment induced a progressive myogenic tone augmentation in mesenteric and olfactory cerebral arteries; neither HFD nor STZ alone had an effect on blood glucose or resistance artery myogenic tone. Using gene deletion models that eliminate tumor necrosis factor (TNF) or sphingosine kinase 1, we demonstrate that vascular smooth muscle cell TNF drives the elevation of myogenic tone via enhanced sphingosine-1-phosphate (S1P) signaling. Therapeutically antagonizing TNF (etanercept) or S1P (JTE013) signaling corrects this defect. Our investigation concludes that vascular smooth muscle cell TNF augments resistance artery myogenic vasoconstriction in a diabetes model that induces a small elevation of blood glucose. Our data demonstrate that microvascular reactivity is an early disease marker and advocate establishing therapies that strategically target the microcirculation.