Sublingual Nitroglycerin Research Articles

Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions

Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a β blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.

Time-course of vascular dysfunction of brachial artery after transradial access for coronary angiography.

Prior studies have demonstrated endothelial and smooth muscle brachial artery dysfunction after transradial cardiac catheterization for diagnostic coronary angiography. The duration of this vascular dysfunction is unknown. To determine the time-course of endothelial and smooth muscle cell dysfunction in the upstream brachial artery after transradial cardiac catheterization. We studied 22 consecutive patients with suspected coronary artery disease (age 64.4 ± 7.7 years) undergoing diagnostic transradial cardiac catheterization. Using high-resolution vascular ultrasound, we measured ipsilateral brachial artery diameter changes during reactive hyperemia (endothelium-dependent dilatation) and administration of sublingual nitroglycerin (endothelium-independent dilatation). The measurements were taken at baseline (before cardiac catheterization), 6 h, 24 h, 1 week, and 1 month postprocedure. The contralateral brachial artery served as a control. Ipsilateral brachial artery diameter during endothelium-dependent dilatation decreased significantly compared with the contralateral diameters at 6 h and 24 h after transradial cardiac catheterization (3.22 vs. 4.11 and 3.29 vs. 4.11, respectively, P < 0.001). The administration of nitroglycerin did not affect this difference. At 1 week and 1 month postprocedure there was no significant difference in diameter of the ipsilateral versus the contralateral brachial artery. As expected the contralateral brachial artery showed no significant changes in diameter. Our results showed that transradial cardiac catheterization causes transient vascular endothelial and smooth muscle dysfunction of the ipsilateral brachial artery, which resolves within 1 week postprocedure. These findings strongly suggest the absence of systemic vascular dysfunction after transradial catheterization both immediately postprocedure as well as 1 week postprocedure. © 2015 Wiley Periodicals, Inc.

Maastricht experience with the second generation endoscopic laser balloon ablation system for the atrial fibrillation treatment.

Gal et al. [1] reported the results of the 50 patients treated for atrial fibrillation (AF) using the endoscopic laser balloon ablation system (EAS) in the Netherlands, who were recruited for the study between December 2011 and December 2013. The second-generation EAS uses a compliant balloon to improve balloon/tissue contact, which improves the energy delivery to create consistent lesions and, ultimately, to achieve durable pulmonary vein (PV) isolation. The study’s mean procedure and fluoroscopy time were 171 and 36 min, respectively. Temporary phrenic nerve palsy was observed during a single procedure. After a median follow-up of 17.3 (12.9–19.5) months, 58 % of the patients remained free of AF, after a single EAS PV isolation without the use of antiarrhythmic drugs. Between November 2012 and July 2013, 24 patients underwent PV isolation using the second-generation EAS at the Maastricht University Medical Center. Oesophageal temperature monitoring was adopted for all patients to avoid undesired excessive oesophageal thermal injury. Acute PV isolation was achieved in all 80 PVs of 20 patients (100 %). The mean procedure and fluoroscopy time were comparable with that of Gal et al., 180 ± 44 and 25 ± 10 min, respectively. In all of these patients except four, a bolus of 15–21 mg of adenosine was injected followed by a rapid saline flush, 30 min after the last energy application [2]. Restoration of electrical conduction by adenosine-mediated hyperpolarisation occurred in 11 PVs (13.7 %) in seven patients (35 %), namely the left superior PV in four, the left inferior PV in two, the right superior PV in four, and the right inferior PV in one. Additional EAS-guided ablation was performed in these veins achieving complete isolation. We did not observe any oesophageal temperature rise above 39 °C for any of the patients. The complication rate was relatively low with one case of spontaneously resolving phrenic nerve palsy, one patient with transient ST-segment elevation conservatively managed by sublingual nitroglycerin, and one groin haematoma. After a 3-month blanking period, patients received a 24–48 h Holter monitor every 3 months for 1 year to assess AF recurrence. Previously, we have reported that of these patients, 85 % were free of AF without antiarrhythmic drugs, after a median follow-up of 267 ± 76.9 days [3]. Currently, after a follow-up of 18.9 ± 2.3 months, the success rate is 81 % [4]. The higher medium-term AF-free survival after EAS-PV isolation at Maastricht may be partly explained by a potentially shorter learning curve due to prior experience with a similar balloon-based ablation system, i.e. cryoballoon. In addition, the elimination of adenosine-mediated PV reconnections may have contributed to the clinical benefit, although the incremental value remains to be resolved. In addition, elimination adenosine-mediated PV reconnections may have increased the overall success rate [5, 6].

Recurrent syncope in two patients with a sigmoid-shaped interventricular septum and no left ventricular hypertrophy

Sigmoid-shaped interventricular septum (SIS) is not uncommon in elderly patients and is considered a normal part of the aging process. However, several patients have been reported to have clinical symptoms due to the narrowing of the left ventricular outflow tract (LVOT). Two patients with SIS presented with recurrent episodes of syncope after drinking or taking sublingual nitroglycerin (NG). In both patients, a head-up tilt test involving provocation with alcohol, NG, or isoproterenol induced the vasovagal reflex along with an increase in the pressure gradient between the apex and LVOT. The patients experienced no further episodes of syncope after initiating bisoprolol treatment. In patients with SIS, induction of the vasovagal reflex via an increase in left ventricular (LV) pressure due to LVOT obstruction concomitant with increased LV construction is a potentially important cause of syncope, which may be effectively prevented by beta-blockers.

Under-pressure: Right Ventricular Infarction

PRESENTATION When a 60-year-old woman’s electrocardiogram (ECG) indicated both anterior and inferior ST-segment elevation myocardial infarction, it was unclear which artery was blocked until treatment with nitroglycerin and morphine rendered her hypotensive. The patient, who had a history of type 2 diabetes mellitus and hypertension, arrived at the emergency department 30 minutes after acute onset of diaphoresis and shortness of breath. The ECG (Figure 1) showed atrial fibrillation, ST-segment elevations in the inferior leads, and reciprocal ST depressions in leads I and aVL. Marked ST-segment elevations were also visible in the anterior leads, V3 and V4. She had a heart rate of 119 beats per minute and a blood pressure of 116/56 mmHg. On physical examination, the patient was in mild distress and diaphoretic. Her cardiovascular examination was significant for tachycardia with an irregularly irregular heartbeat. She was treated immediately with aspirin, clopidogrel, and heparin. A few minutes later, she was given sublingual nitroglycerin and a bolus dose of intravenous morphine. Shortly after receiving the nitroglycerin and morphine, her blood pressure dropped to 72/49 mmHg. She was hydrated aggressively and taken to the cardiac catheterization laboratory for coronary angiography.

Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review.

ObjectiveTo systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography.MethodsA systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied.ResultsOf the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention.ConclusionSublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes.Key Points• Sublingual nitroglycerin administration results in significant coronary artery dilatation.• Nitroglycerin increases the number of evaluable coronary branches.• Image quality is improved the most in smaller coronary branches.• Nitroglycerin increases the diagnostic accuracy of coronary CT angiography.• Most side effects are mild and do not require medical intervention.

Complications Associated With Nitrate Use in Patients Presenting With Acute Pulmonary Edema and Concomitant Moderate or Severe Aortic Stenosis

We evaluate the incidence of complications associated with the use of nitrates in patients presenting with acute pulmonary edema and concomitant moderate or severe aortic stenosis compared with patients without aortic stenosis. Nitrates are contraindicated in severe aortic stenosis because of the theoretical yet unproven risk of precipitating profound hypotension. A cohort design with retrospective chart review study was conducted at two Canadian hospitals. Patients with aortic stenosis (moderate or severe) and without aortic stenosis were included if they presented with acute cardiogenic pulmonary edema, received intravenous or sublingual nitroglycerin, and had an echocardiography report available. The primary outcome was clinically relevant hypotension, defined as hypotension leading to any of the following predefined events: nitroglycerin discontinuation, intravenous fluid bolus, vasopressor use, or cardiac arrest. The secondary outcome was sustained hypotension, defined as a systolic blood pressure less than 90 mm Hg and lasting greater than or equal to 30 minutes. The cohort consisted of 195 episodes of acute pulmonary edema, representing 65 episodes with severe aortic stenosis (N=65) and an equal number of matched episodes with moderate aortic stenosis (N=65) and no aortic stenosis (N=65). Nitroglycerin was administered intravenously only in 70% of cases, intravenously and sublingually in 25%, and sublingually only in the remaining 5%. After adjustment for sex, initial systolic blood pressure, furosemide dose, and use of noninvasive ventilation, moderate and severe aortic stenosis were not associated with clinically relevant hypotension after receipt of nitroglycerin (adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.40 to 2.37 for moderate aortic stenosis; adjusted OR 0.99, 95% CI 0.41 to 2.41 for severe aortic stenosis). The incidence of clinically relevant hypotension was 26.2% for moderate and severe aortic stenosis and 23.1% in the no aortic stenosis reference group. The secondary outcome of sustained hypotension occurred in 29.2% of patients with severe aortic stenosis, 16.9% with moderate aortic stenosis, and 13.8% in the no aortic stenosis group (adjusted OR for severe aortic stenosis 2.34; 95% CI 0.91 to 6.01). In this retrospective study, neither moderate nor severe aortic stenosis was associated with a greater risk of clinically relevant hypotension requiring intervention when nitroglycerin was used for acute pulmonary edema. Future studies should investigate safety and efficacy of nitroglycerin for patients with aortic stenosis because this study was limited by a small sample size and design limitations. Cautious use of nitroglycerin in patients with moderate or severe aortic stenosis and presenting with acute pulmonary edema may be a safer strategy than traditionally thought.

Escala de Calgary para el diagnóstico del síncope vasovagal. Estudio de pruebas diagnósticas

ObjectiveEvaluate the utility of Calgary score for the diagnosis of vasovagal syncope compared with the results of the Tilt table test using sensibilized protocol with medicines. MethodologyProspective study of diagnostic tests in patients with suspected diagnostic of vasovagal syncope who underwent tilt table test with induced vasodilation with sublingual nitroglycerin. Patients over 18 years were included and patients with documented structural heart disease were excluded. Results100 patients were analyzed, averaging 48.7 years of age (SD 19.7), 69% of feminine genre and 4% residents in rural area. Medium of syncope at the moment of tilt table test was 5 (IQR 2-15), with presentation of first episode at 41 years (IQR 21-57), in 52% of the patients triggers were not identified and the clinical manifestations referred in episodes previous to Tilt test were diaphoresis (58%), pallor (55%), dizziness (70%), palpitations (50%) and nausea (42%); during the test dizziness (65%), diaphoresis (19%), nausea (18%) and blurred vision (18%) were reported. A sensitivity of 77.7% was obtained (95% CI 88.8 66.7) and specificity of 40.5% (95% CI 23.3 - 57.7) for the Calgary score. ConclusionsDue to its high sensitivity and easy application, the Calgary score is a useful diagnostic approach instrument for patients with suspected vasovagal syncope and who have a structurally healthy heart, especially in those younger than 50 years.

Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study.

BackgroundThere is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls.MethodsHealthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated.ResultssVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR.ConclusionOxidized-LDL and sVCAM might be used as endothelial dysfunction biomarkers for elderly with normal cardiovascular risk factors.

Effect of smoking on endothelium-independent vasodilatation

BackgroundSmoking induces an impairment of endothelium-dependent vasodilatation. In this study we assessed whether smoking also causes an impairment of endothelium-independent vasodilatation. MethodsWe studied 2 groups of young healthy subjects: 1) 12 medical students (24.5 ± 0.9 years; 6 male) without cardiovascular risk factors (CVRFs), except smoking (≥10 cigarettes/day); 2) 12 matched controls (24.5 ± 1.1 years; 6 male) without any CVRF. Nitrate-mediated dilatation (NMD) of the brachial artery was assessed in response to the random administration of 4 different doses (10, 20, 30 and 40 μg) of sublingual nitroglycerin (NTG). Flow-mediated dilatation (FMD) was also assessed. ResultsThe increasing doses of NTG determined a progressive increase of NMD in both groups, but the dose–response curve was significantly lower in smokers compared to controls (p < 0.001). FMD was also lower in smokers, compared to controls (6.12 + 0.6 vs. 8.06 + 0.9%, p < 0.001). ConclusionsOur data show that smoking induces an early impairment of endothelium-independent arterial dilatation.

Abstract W P60: Blood Pressure Reduction In Acute Ischemic Stroke Does Not Affect Ischemic Core Tissue Perfusion

Introduction: Blood pressure (BP) reduction in acute ischemic stroke patients can potentially decrease cerebral blood flow (CBF) in ischemic tissue due to disrupted autoregulation, particularly in the ischemic core. We tested this hypothesis using a 3 group non-randomized controlled study of serial CBF measurements in ischemic stroke patients. Methods: Patients with acute ischemic stroke ≤72h of symptom onset were recruited. Groups were assigned according to baseline mean arterial blood pressure (MAP): patients with MAP &gt;120mmHg were treated with intravenous labetalol and sublingual (SL) nitroglycerin and those with MAP 100-120 mmHg were treated with SL nitroglycerin. The BP reduction target was 10% of the baseline MAP. Patients with MAP&lt;100 mmHg formed the control group. Patients underwent MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) before and after BP reduction. Blinded planimetric assessment was done to determine PWI deficits and DWI lesion volumes in the ischemic core region. Results: A total of 48 patients with mean±SD age of 65.4±13.2 years were enrolled at 23.4±15.3h after symptom onset. The mean time difference between perfusion scans was 25.6±9.5 min.Median(IQR) DWI volume was 11.1 (96.8) ml. Mean MAP was 126±7.5 mmHg in the MAP&gt;120 group(n=13), 109.9±4.9 mmHg in the MAP 100-120 group (n=16), and 89.9±6.2 mmHg in the controls (n=19). Mean BP reduction in the treated patients was 11.9±6.7 mmHg (95% CI 15.6-3; p=0.04). Baseline mean relative CBF (rCBF) in ischemic core tissue was 1.1±0.47 in the MAP &gt;120 group, 0.87±0.35 in the MAP 100-120 group and 0.78±0.32 in controls. The mean change in rCBF following BP reduction did not differ between the MAP &gt;120 group (0.03±0.17), MAP 100-120 group (0.06±0.17) and controls (0.08±0.25) (p=0.28). Similarly, there was no difference in the mean relative cerebral blood volume (p=0.3) and relative mean transit time (p=0.58) before and after BP reduction. In patients treated with SL nitroglycerin (n=17), there was no improvement in mean lesional rCBF (0.04±0.17 vs.-0.02±0.18, p=0.25). Conclusion: Modest BP reduction does not lead to an immediate decrease in CBF, within the ischemic core. Acute antihypertensive therapy may be less directly harmful than has been postulated.

Positive effect of sublingual nitroglycerin on performance of non-contrast enhanced magnetic resonance coronary angiography

Background Cardiac magnetic resonance imaging (CMR) is increasingly proposed for non-invasive detection of relevant coronary artery disease (CAD), currently using an integrated assessment of myocardial perfusion, viability and function. Magnetic resonance coronary artery imaging (MRCA) is still experimental. Currently, it is not proven if sublingual nitroglycerin (slNitro) should be given to enhance performance of MRCA. Methods 15 volunteers, 9 (60%) of them male, mean age 37.2 years (±11) without known CAD underwent MRCA, without and with slNitro. slNitro dosage was adjusted according to blood pressure (systolic blood pressure (BP) >180 mmHg =>1.6 mg glyceroltrinitrat, BP 140-179 mmHg =>1.2 mg, BP 100-139 mmHg =>0.8 mg, BP 90-100mmHg =>0.4mg). All volunteers were examined in supine position using a GE Signa HDxt 1.5 Tesla scanner, equipped with EchoSpeed gradients, and a dedicated 8-element phased array cardiac coil (GE Healthcare, Milwaukee, Wisconsin). For imaging of the coronary arteries a commercially available whole heart 3D navigator gated multislab steady state free precession sequence (3D HEART, based on 3D FatSat FIESTA) without the administration of contrast medium was employed. This sequence is designed for free breathing cardiac MR angiography, using a navigator echo pulse that detects motion of the diaphragm. We used an abdominal belt in all vol to reduce motion of the diaphragm. Post processing was perfomed with cvi 42 5.0 (Circle, Calgary, Canada). Vessel diameter was measured before and after slNitro. Image quality was graded visually before and after slNitro on a 4-point scale: 1 = non-assessable with severe image artifacts, poor vessel contrast; 2 = assessable with

“Requiring Intravenous Nitroglycerin” Should be considered a High Risk Feature in Patients with Non-ST Elevation Myocardial Infarction and Unstable Angina

Introduction: Early risk stratification of patients with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) is crucial to identify those at high risk for further cardiac events as they may benefit from an early invasive strategy of coronary angiography and revascularization. The TIMI score, a widely used predictive model to guide management strategy in UA and NSTEMI may not accurately stratify risk. Case description: A 63-year-old man, who is an active smoker with past medical history of hypertension and dyslipidemia, presented with severe sub-sternal, crushing chest pain, which began four hours prior to presentation. His EKG revealed sinus tachycardia, without ST segment deviations or Q waves. He received aspirin, three doses of sublingual nitroglycerin and metoprolol, but continued to have chest pain, thus he was commenced on intravenous nitroglycerin infusion. His chest pain went away after two hours on nitroglycerin infusion. His initial serum troponin I was 0.31 ng/mL and 3.60 ng/mL four hours after presentation. He was admitted for NSTEMI and started on clopidogrel, atorvastatin and intravenous heparin. Echocardiogram revealed inferio-septal wall a kinesis and severely reduced left ventricular systolic function. His troponin I continued to rise, peaking at 37.4 ng/mL. He was started on eptifibatide and was referred for coronary angiography and percutaneous coronary intervention, with finding of fifty percent proximal and distal left anterior descending artery (LAD) lesions. Discussion: With a TIMI score of 2, our patient was classified as low risk at presentation. The need for intravenous nitroglycerin infusion for continuing chest pain in the management of UA or NSTEMI may suggest a greater degree of myocardial ischemia and a higher risk for adverse cardiovascular outcomes. This case demonstrates that UA and NSTEMI patients requiring intravenous nitroglycerin initially planned for conservative therapeutic approach need continuous risk stratification which may dictate a change to the invasive management strategy.

Effect of aldehyde dehydrogenase 2 gene polymorphism on hemodynamics after nitroglycerin intervention in Northern Chinese Han population.

Background:Nitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population.Methods:This study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes.Results:Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05).Conclusion:ALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Evaluation of Pharmacologic Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review

There is controversy over the efficacy of pharmacologic agents for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). We performed a systematic review of PEP pharmacoprevention to evaluate safety and efficacy. We performed a systematic search of the literature for randomized controlled trials (RCTs) and meta-analyses of PEP pharmacoprevention through February 2014. After identifying relevant studies, 2 reviewers each extracted information on study characteristics, clinical outcomes, and risk of bias. A research classification scale was developed to identify pharmacologic agents ready for clinical use, agents for which a confirmatory RCT should be considered a high priority, agents for which exploratory studies are still necessary, and agents for which additional research should be of low priority. Clinical and research recommendations for each agent were made by consensus after considering research classification results and other important factors such as magnitude of benefit, safety, availability, and cost. After screening 851 citations and 263 potentially relevant articles, 2 reviewers identified 85 RCTs and 28 meta-analyses that were eligible. On the basis of these studies, rectal nonsteroidal anti-inflammatory drugs were found to be appropriate for clinical use, especially for high-risk cases. Sublingual nitroglycerin, bolus-administered somatostatin, and nafamostat were found to be promising agents for which confirmatory research is warranted. Additional research was found to be required to justify confirmatory RCTs for topical epinephrine, aggressive intravenous fluids, gabexate, ulinastatin, secretin, and antibiotics. On the basis of a systematic review, NSAIDs are appropriate for use in prevention of PEP, especially for high-risk cases. Additional research is necessary to clarify the role of other pharmacologic agents. These findings could inform future research and guide clinical decision-making and policy.

Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes

AimIrisin is first discovered as a potential mediator of obesity related energy homeostasis. Recent studies indicate that irisin is associated with endothelial dysfunction and atherosclerosis in patients with type 2 diabetes. Our objective was to examine the relationship between irisin and urinary albumin excretion in patients with type 2 diabetes. Methods100 newly diagnosed patients with type 2 diabetes and 100 healthy subjects were selected. Serum irisin levels were measured by ELISA, and urine albumin was measured by radioimmunoassay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated arterial dilation, FMD) and after sublingual glyceryltrinitrate. ResultsPatients with type 2 diabetes presented decreased irisin levels when compared to controls (14.12±3.93 versus 28.98±2.56ng/ml, P=0.015).Serum irisin levels in the microalbuminuric and macroalbuminuria subgroup were 9.89±1.56ng/ml and 5.67±1.89ng/ml, respectively, which were significantly lower than those in the normoalbuminuria (15.97±3.12ng/ml). In comparison to microalbuminuric subgroup, macroalbuminuria subgroup had lower levels of irisin. By dividing the distribution of serum irisin levels into quartiles, FMD was increased gradually with the increase of serum irisin levels (P<0.001). Multiple stepwise linear regression analysis showed that FMD (β=0.75, P=0.002), 2-hBG (β=−0.25, P=0.038) and UAE (β=−0.87, P=0.008) were significantly associated with irisin. Pearson's correlation analyses showed a negative correlation between irisin and logUAE (r=−0.57) and between FMD and logUAE (r=−0.47), and positive correlations between irisin and FMD (r=0.51). ConclusionsDecreased plasma levels of irisin seem to be associated with UAE and FMD in patients with type 2 diabetes.

Prueba de basculación (Tilt Table Testing): Comparación de dos protocolos: isoproterenol versus nitroglicerina

There is debate about the advantages of different protocols usefulness of tilt test for the diagnosis of vasovagal collapse. To compare the sensitivity, specificity, adverse reactions, complications and time requirements of two different Tilt test protocols. A Tilt test using isoproterenol in progressive doses (2 μg for 10 min and 5 μg for 5 min posteriorly was performed in 159 patients aged 9 to 84 years (59 males). Another Tilt test using sublingual nitroglycerine in doses of 0.3 mg was performed in 201 patients aged 8 to 87 years (62 males). Also, 20 healthy volunteers were tested. The positivity rates of the tests using isoproterenol and nitroglycerin were 75.5 and 77.6% respectively (NS). The figures for sensitivity were 98.4 and 99.3% (NS). The figures for specificity were 93.2 and 98.4% (NS). The test using isoproterenol requires 15 more minutes. As adverse reactions, 38% of participants experienced palpitations with isoproterenol and 22% experienced headache with nitroglycerin. The Tilt test with nitroglycerin is shorter, simpler, painless, with less personnel involved and has the same diagnostic accuracy than the test with isoproterenol.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

Background & objectives:Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease.Methods:Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations.Results:The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI > 30 kg/m2). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex.Interpretation & conclusions:The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

Age and the Head-Up Tilt Test Outcome in Syncope Patients.

Background:The head-up tilt test (HUTT) is a useful diagnostic tool for syncope.Objectives:We sought to investigate the outcome of the HUTT in syncope patients and identify the relationship between age and different hemodynamic outcomes.Patients and Methods:In this cross-sectional study, we prospectively enrolled consecutive patients who presented with syncope and underwent the HUTT with a clinical suspicion of neurocardiogenic syncope after the exclusion of orthostatic hypotension cases. The HUTT consisted of consecutive passive and active phases. In the passive phase, the patients were tilted at 70 degrees for 20 minutes; and if negative, the test was repeated with 400 micrograms of sublingual nitroglycerin for another 20 minutes. Positive responses were classified according to the classification of the vasovagal syncope international study (VASIS) and compared for age and gender.Results:A total of 498 patients were enrolled (age = 44.93 ± 18.77 years; male = 271 [54.4%]). Overall, 291 (58.4%) patients had a positive HUTT, while 256 (88.5%) patients had a positive result during the active phase. The test results were as follows: 107 (36.7%) mixed type (VASIS I), 103 (35.3%) cardioinhibitory (VASIS IIA = 44 [15.1%]; VASIS IIB = 59 [20.2%]), and 80 (27.4%) vasodepressive (VASIS III). There was no relationship between gender and syncope type. The trend of the HUTT result significantly changed with age, and the rate of cardioinhibitory syncope decreased after middle ages (P value for trend = 0.02).Conclusions:Hemodynamic response to the HUTT was associated with age. Cardioinhibitory response became less frequent with age due to exaggerated vagal activity in the younger patients as compared with the older subjects.

Probable hydrochlorothiazide-induced myopericarditis: first case reported.

Hydrochlorothiazide has never been reported as a reason for myopericarditis. An African American female, with past history of hypertension, coronary artery disease, and sulfa allergy, presented with indolent onset and retrosternal chest pain which was positional, pleuritic, and unresponsive to sublingual nitroglycerin. Her medications included hydrochlorothiazide (HCTZ) which was started three months ago for uncontrolled hypertension. Significant laboratory parameters included erythrocyte sedimentation rate (ESR) of 47 mm/hr and peak troponin of 0.26 ng/mL. Transthoracic echocardiogram (TTE) revealed preserved ejection fraction with no segmental wall motion abnormalities; however, it showed moderate pericardial effusion without tamponade physiology. We hypothesize that this myopericarditis could be due to HCTZ allergic reaction after all other common etiologies have been ruled out. There is a scarcity of the literature regarding HCTZ as an etiology for pericardial disease, with only one case reported as presumed hydrochlorothiazide-induced pericardial effusion. Management involves discontinuation of HCTZ and starting anti-inflammatory therapy.