Huay-Cheem Tan

Obstructive Sleep Apnea in Patients Admitted for Acute Myocardial Infarction: Prevalence, Predictors, and Effect on Microvascular Perfusion

BACKGROUND We investigated the prevalence and predictors of obstructive sleep apnea (OSA) in patients admitted to the hospital for acute myocardial infarction and whether OSA has any association with microvascular perfusion after primary percutaneous coronary intervention (PCI). METHODS Recruited patients were scheduled to undergo an overnight sleep study between 2 and 5 days after primary PCI. An apnea-hypopnea index (AHI) of > or = 15 was considered diagnostic of OSA. Impaired microvascular perfusion after primary PCI was defined as an ST-segment resolution of < or = 70%, myocardial blush grade 0 or 1, or a corrected Thrombolysis in Myocardial Infarction (TIMI) [antegrade flow scale] frame count > 28. RESULTS Sleep study was performed in 120 patients and completed in 105 patients (study cohort, mean age 53 +/- 10 years, male 98%) with uncomplicated myocardial infarction. An AHI was > or = 15 in 69 patients (OSA-positive), giving a prevalence of 65.7%. Diabetes mellitus was found to be a significant risk factor for OSA (odds ratio, 2.86; 95% confidence interval, 1.06 to 8.24; p = 0.033). There were no differences between OSA-positive and OSA-negative groups with regard to the percentage of patients with < or = 70% ST-segment resolution (73% vs 64%, respectively; p = 0.411), myocardial blush grade 0 or 1 (39.1% vs 38.9%, respectively; p = 1.000), or corrected TIMI frame count > 28 (21.7% vs 25.0%, respectively; p = 0.807). CONCLUSIONS We found a high prevalence of previously undiagnosed OSA in patients admitted with acute myocardial infarction. Diabetes mellitus was independently associated with OSA. No evidence indicated that OSA is associated with impaired microvascular perfusion after primary PCI.

Usefulness of ST elevation II/III ratio and ST deviation in lead I for identifying the culprit artery in inferior wall acute myocardial infarction.

In a study of 92 patients presenting with inferior wall acute myocardial infarction, the infarct-related artery was the right coronary artery in 72 patients (78%) and the left circumflex artery in 20 (22%). An ST II/III ratio of 1 or an isoelectric ST in lead I are sensitive and specific markers of left circumflex artery occlusion, whereas an ST II/III ratio <1 (ST elevation in lead III >II) or ST depression in lead I are sensitive and specific markers of right coronary artery occlusion.

The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent.

OBJECTIVES This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months. BACKGROUND Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations. METHODS One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events. RESULTS The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group. CONCLUSIONS In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.

New Set of Intravascular Ultrasound-Derived Anatomic Criteria for Defining Functionally Significant Stenoses in Small Coronary Arteries (Results from Intravascular Ultrasound Diagnostic Evaluation of Atherosclerosis in Singapore (IDEAS) Study)

We sought to determine the intravascular ultrasound-derived anatomic criteria for functionally significant lesions in small coronary arteries with a reference segment diameter <3 mm. A fractional flow reserve (FFR) of <0.75, as determined by pressure wire using high-dose (100 to 150 microg) intracoronary adenosine, was used as the reference standard for functional significance. For the 94 patients/lesions involved in the present study, the average reference vessel diameter was 2.72 mm. The FFR was <0.75 in 38 patients (40.4%) and > or =0.75 in 56 patients (59.6%). Logistic regression analysis identified the minimal lumen area, plaque burden, and lesion length as the 3 most important determinants of the FFR. Using classification and regression tree analysis, the best cutoff values for these determinants to discriminate a FFR of <0.75 versus > or =0.75 were a minimal lumen area of < or =2.0 mm(2) (sensitivity 82.35%, specificity 80.77%), plaque burden of > or =80% (sensitivity 87.9%, specificity 78.9%), and lesion length of > or =20 mm (sensitivity 63.6%, specificity 78.9%). A significant increase was found in the area under the receiver operating characteristic curve of the combined parameters (minimal lumen area plus plaque burden plus lesion length) compared to the plaque burden (p = 0.014) and other individual parameters (p <0.001). In conclusion, we found that intravascular ultrasound-derived anatomic criteria are able to predict the functional significance of intermediate lesions in small coronary arteries. A minimal lumen area of < or =2.0 mm(2), plaque burden of > or =80%, and lesion length of > or =20 mm predicted a FFR of <0.75 with good sensitivity and specificity.

Severe obstructive sleep apnea and outcomes following myocardial infarction.

STUDY OBJECTIVE We sought to determine the effect of severe obstructive sleep apnea (OSA) on long-term outcomes after myocardial infarction. We hypothesized that severe OSA was associated with lower event-free survival rate after ST-segment elevation myocardial infarction (STEMI). METHODS A total of 120 patients underwent an overnight sleep study during index admission for STEMI. Severe OSA was defined as apnea hypopnea index (AHI) ≥ 30, and non-severe OSA defined as AHI < 30. RESULTS Among the 105 patients who completed the study, 44 (42%) had severe OSA and 61 (58%) non-severe OSA. The median creatine kinase level and mean left ventricular systolic function were similar between the 2 groups. None of the 105 study patients had received treatments for OSA. Between 1- and 18-month follow-up, the severe OSA group incurred 1 death, 2 reinfarctions, 1 stroke, 6 unplanned target vessel revascularizations, and 1 heart failure hospitalization. In contrast, there were only 2 unplanned target vessel revascularizations in the non-severe OSA group. The incidence of major adverse events was significantly higher in the severe OSA group (15.9% versus 3.3%, adjusted hazard ratios: 5.36, 95% CI: 1.01 to 28.53, p = 0.049). Kaplan-Meier event-free survival curves showed the event-free survival rates in the severe OSA group was significantly worse than that in the non-severe OSA group (p = 0.021, log-rank test). CONCLUSION 42% of the patients admitted with STEMI have undiagnosed severe OSA. Severe OSA carries a negative prognostic impact for this group of patients. It is associated with a lower event-free survival rate at 18-month follow-up.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention

Background— There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. Methods and Results— The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. Conclusions— OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Everolimus-eluting bioresorbable vascular scaffold (BVS) implantation in patients with ST-segment elevation myocardial infarction (STEMI).

AIMS Recent studies have demonstrated favourable clinical outcomes for the everolimus-eluting bioresorbable vascular scaffold (BVS) ABSORB™ in patients with stable coronary artery disease. There are currently no data on its use in patients with ST-segment elevation myocardial infarction (STEMI). We assessed the safety and impact of BVS in the setting of primary percutaneous coronary intervention (PCI) in patients presenting with STEMI to our institution. METHODS AND RESULTS A total of 11 patients who underwent primary PCI with intent for BVS implantation between October 2012 and April 2013 at our institution were included. Median follow-up period was 53.0 ± 45.9 days. One patient presented to the hospital with cardiogenic shock and subsequently died. The other 10 patients did not have any major adverse cardiac events (MACE). There were no acute or subacute stent thromboses at short-term follow-up. CONCLUSIONS These are the first real-world data using BVS in patients with STEMI. The ABSORB™ BVS may be safely used in patients with STEMI undergoing primary PCI with favourable short-term outcome.

Endothelial progenitor cell capture stent implantation in patients with ST-segment elevation acute myocardial infarction: one year follow-up

AIMS The Genous endothelial progenitor cell (EPC) capture stent is a bioengineered R stent coated with immobilised antibodies on its stent struts to allow for the capture of circulating EPCs to promote rapid endothelisation. We assessed the impact of this stent in the primary percutaneous coronary intervention (PCI) of patients with acute ST-elevation myocardial infarction (STEMI) and examined its long term clinical outcomes. METHODS AND RESULTS All patients with acute STEMI without cardiogenic shock who underwent primary PCI between January 2005 and April 2007 and received the stent were enrolled in the study. The study endpoints were major adverse cardiac events (MACE) defined as death, MI and target vessel revascularisation (TVR) at 30 days, six months and one year. A total of 321 enrolled patients received 357 EPC capture stents during the study period. The cohort comprises 81.0% males with mean age of 54.6+/-11.6 years. The mean stent length used was 20.98+/-5.50 mm and mean stent size was 2.99+/-0.32 mm. Ninety-four percent of patients achieved Thrombolysis in Myocardial Infarction (TIMI) 3 flow post-procedurally. The cumulative MACE rate was 8.1% at 30 days, 10.0% at six months and 12.2% at one year. There was one patient who developed acute stent thrombosis and another two with subacute stent thromboses. No late thrombosis or late cardiac mortality was observed in our cohort. The need for TVR was 4.4% at one year. CONCLUSIONS The use of EPC capture stents in patients who underwent primary PCI for STEMI is safe and showed good clinical outcomes, with low rates of TVR and no late stent thrombosis.

Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions.

BACKGROUND Contrast nephropathy (CIN) increases adverse clinical outcomes. We examine risks and clinical predictors of CIN in patients undergoing percutaneous coronary intervention (PCI) and effectiveness of prophylactic therapy. METHODS A cohort of 8,798 patients who underwent PCI from May 2000 to April 2008 was enrolled. We divided patients into 3 groups. A: STEMI patient undergoing primary PCI; B: UA/NSTEMI patients undergoing early PCI; C: Patients without MI undergoing elective PCI. Pre-PCI saline hydration was given to group B and C if baseline glomerular filtration rate (GFR) <60 ml/min/1.73 m². RESULTS Mean age was 57.4 years; 35.9% was diabetics. Incidence of CIN were 12.0%, 9.2%, and 4.5%, in group A, B and C (P = <0.0005). CIN correlated with higher mortality (15.5% vs. 1.3%, P < 0.0005) at 1 month. The important predictors of CIN were age >70, female gender, anemia, low systolic BP < 100 mmHg, high creatinine kinase level, abnormal LVEF, baseline renal impairment, MI and insulin dependent diabetes. Incidence of CIN in patients with GFR >60 were 8.2%, 9.2%, and 4.3% in group A, B, and C respectively (p < 0.0005). Incidence of CIN in patients with GFR = 30-60 were 19.1%, 4.5%, and 2.4% (p < 0.0005) and in patients with GFR < 30 were 34.4%, 40.0%, and 25.9% (p = 0.510). CONCLUSIONS Pre-hydration prophylaxis was effective in preventing CIN in mild renal impaired patients (GFR 30-60) but are less so in more severely renal impaired patients (GFR < 30). STEMI patients undergoing primary PCI regardless of baseline GFR were at high risk. Accelerated prophylactic regime can be considered in this cohort.

Reducing ischaemia/reperfusion injury through δ-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling

AIMS The purpose of this study was to determine whether intrinsic cardiac adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting synergistic adrenopeptidergic cardioprotection. METHODS AND RESULTS In situ hybridization coupled with immunostaining demonstrated that ICA cells exclusively expressed CGRP mRNA and co-expressed CGRP and delta-opioid receptor in human and rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP release from ICA cells in human and rat hearts. The delta-opioid agonist [D-Pen(25)]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with DPDPE reduced infarct size (IS) by 51 +/- 16% (P < 0.01). Co-infusion of beta(2)-adrenergic receptor (beta(2)-AR) and CGRP receptor (CGRP-R) antagonists increased IS by 62 +/- 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS reduction. Pre-treatment of ICA cell-myocyte co-culture with the beta(2)-AR/CGRP-R antagonists increased myocyte death rate by 24 +/- 4% (P < 0.01) and abolished DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O(2)). In the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection. Supplementing ICA cell-depleted myocyte culture with beta(2)-AR/CGRP-R agonists reduced hypoxia/re-O(2)-induced myocyte death by 24 +/- 5% (P < 0.01), simulating endogenous neurohormonal effects of ICA cells. Western blot analysis showed that DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was abolished in the presence of beta(2)-AR/CGRP-R blockade. Terminal dUTP nick-end labelling staining analysis of the LV infarct zone demonstrated that DPDPE reduced myocyte apoptosis by 58 +/- 19% (P < 0.05), an effect that was eliminated in the presence of beta(2)-AR/CGRP-R blockade. Finally, echocardiography showed that DPDPE increased LV contractility in a manner dependent on beta-AR/CGRP-R stimulation. CONCLUSION ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.