Abstract Mental and physical stress is thought to play an important causative factor in apical ballooning syndrome (ABS) likely secondary to the vasomotor dysfunction. However, there are currently few data related to the impact of physical stress in this unique cardiomyopathy. A total 18 patients, including 8 females with history of ABS and 10 post-menopausal controls, underwent physical and mental tests. Assessments included the pain-induced peripheral artery tonometry scores (PIPATs) and mental stress peripheral artery tonometry scores (PATs). Compared with control group, PIPATs were significantly attenuated in patients with ABS in both baseline and post-mental stress (0.94 ± 0.08 vs1.30 ± 0.54, P <.05 and 0.87 ± 0.19 vs1.24 ± 0.21 P = .01, respectively); mental stress PATs were significantly lower in patients with ABS, both in Stroop test (0.79 ± 0.30 vs 1.24 ± 0.43, P = .01) and arithmetic test (0.91 ± 0.27 vs 1.36 ± 0.57, P = .01). PIPATs correlated significantly with mental stress PATs, both in arithmetic and Stroop test (P <.05). The PIPATs were attenuated in female with history of ABS and the vascular response to pain may provide a different pathogenesis mechanism on detecting patients with ABS.
Left Internal Mammary Artery Versus Coronary Stents: Impact on Downstream Coronary Stenoses and Conduit Patency
Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery ( LIMA ) versus percutaneous coronary intervention with bare metal stent ( BMS ) or drug eluting stent ( DES ). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography ( QCA ; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [ HR ] [95% CI ], 0.34; [0.20–0.59]; P =0.0002; and HR [95% CI ], 0.39; [0.20–0.79]; P =0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES ( HR [95% CI ], 0.18; [0.12–0.28]; P <0.001; and HR [95% CI ], 0.27; [0.16–0.46]; P <0.001, respectively). BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES , but the difference did not reach statistical significance ( HR [95% CI], 1.13; [0.57–2.36]; P =0.73; and HR [95% CI ], 1.46; [0.88–2.50]; P =0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES .
Age‐Dependent Predictive Value of Endothelial Dysfunction for Arrhythmia Recurrence Following Pulmonary Vein Isolation
Background The mechanisms of atrial fibrillation (AF) are highly divergent. The prevalence of AF increases significantly with age, and underling mechanisms might vary with age. Endothelial dysfunction may be associated with AF and atrial arrhythmia recurrence after catheter ablation. We tested the hypothesis that the impact of endothelial dysfunction on arrhythmia recurrence following catheter ablation is age dependent. Methods and Results This study enrolled 92 participants with AF undergoing catheter ablation. Endothelial function was assessed by peripheral arterial tonometry before ablation, and the natural logarithmic transformation of reactive hyperemia index was calculated. Endothelial dysfunction was defined as a natural logarithmic transformation of reactive hyperemia index <0.618 (median). Participants were followed for atrial tachycardia, flutter, and fibrillation recurrence for a median of 14 months. The mean age was 57±10 years. There was significant interaction between age and endothelial dysfunction in association with recurrence of AF ( P =0.029) and any atrial arrhythmia ( P =0.015), and the risk associated with endothelial dysfunction for arrhythmia recurrence was higher in younger versus older participants. Participants were divided into 2 age groups at a threshold of 60 years. Among participants aged ≤60 years, multivariate Cox proportional hazards analysis revealed the independent association between endothelial dysfunction and increased risk of arrhythmia recurrence (hazard ratio for AF 4.18 [95% CI 1.33–15.82], P =0.014, and for any atrial arrhythmia 3.62 [95% CI 1.29–11.81], P =0.014). Kaplan–Meier analysis showed that participants with endothelial dysfunction had significantly higher rates of recurrence of AF ( P =0.01) and any atrial arrhythmia ( P =0.002). Conclusions The risk associated with endothelial dysfunction for arrhythmia recurrence following catheter ablation was age dependent and was higher in younger participants.
Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial
Objectives Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow. Methods In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified. Results Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (−17 (−26, −10) vs 26 (−15, 134); p=0.02 and −17 (−38, 14) vs 107 (2, 446); p=0.007, respectively). Conclusions Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI. Trial registration number NCT00586820; Results.
Prognostic Value of Flow‐Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta‐Analysis
Background Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events. Methods and Results Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91], P <0.001, 0.1 increase in Ln_RHI 0.79 [0.71–0.87], P <0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk. Conclusions Noninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.
Secondary Prevention Strategy of Cardiovascular Disease Using Endothelial Function Testing
Background Cardiac allograft vasculopathy is the leading cause of graft failure and death in heart transplant ( HT x) recipients; however, the association between the etiology of heart failure (ischemic cardiomyopathy [ ICM ] or non‐ ICM ) that led to HT x and progression of c ardiac allograft vasculopathy , and adverse events after HT x has not been explored. Methods and Results We retrospectively included 165 HT x patients, who were followed‐up with at least 2 virtual histology–intravascular ultrasound examinations after HT x, and grouped them as ICM (n=46) or non‐ ICM (n=119). Coronary artery plaque volume was analyzed using virtual histology–intravascular ultrasound, and cardiovascular event data—a composite of myocardial infarction, hospitalization for heart failure and arrhythmia, revascularization, retransplantation, and death including cardiovascular death—were collected from the medical records of all study subjects. ICM patients had significantly higher plaque volume at both first ( P =0.040) and follow‐up ( P =0.015) intravascular ultrasound examinations. After multivariate adjustment for traditional coronary risk factors, ICM was significantly associated with plaque progression (odds ratio 3.10; CI 1.17 to 9.36; P =0.023). Ten‐year cardiovascular event‐free survival was 50% in ICM patients compared with 84% in non‐ ICM patients (log‐rank test P =0.003). In multivariate Cox proportional hazard analysis, ICM was significantly associated with a higher event rate after HT x (hazard ratio 2.02; 95% CI 1.01 to 4.00; P =0.048). Conclusion Our study demonstrates that ischemic etiology of cardiomyopathy prior to HT x may be independently associated with plaque progression and higher event rate after HT x.