Nocturnal Angina Research Articles

The Impact of Head-Up Tilt Sleeping on Orthostatic Tolerance: A Scoping Review.

To systematically summarize the evidence of head-up tilt sleeping (HUTS) on orthostatic tolerance, we conducted a systematic, predefined search in PubMed, OVID Embase, Cochrane and Web of Science. We included studies assessing the effect of HUTS on orthostatic tolerance and other cardiovascular measures and rated the quality with the American Academy of Neurology risk of bias tool. We included 10 studies (n = 185) in four groups: orthostatic hypotension (OH; 6 studies, n = 103), vasovagal syncope (1 study, n = 12), nocturnal angina pectoris (1 study, n = 10) and healthy subjects (2 studies, n = 58). HUTS duration varied (1 day-4 months) with variable inclinations (5°-15°). In two of six OH studies, HUTS significantly improved standing systolic blood pressure. Orthostatic tolerance was consistently enhanced in OH studies with higher angles (≥12°), in 2 out of 3 with smaller angles (5°) but also in one studying horizontal sleeping. In vasovagal syncope, HUTS significantly augmented resilience to extreme orthostatic stress. One study was rated as a class II risk of bias, one of Class II/III and eight of Class IV. The evidence favouring HUTS to improve orthostatic tolerance is weak due to variable interventions, populations, small samples and a high risk of bias. Despite this, we found some physiological signs suggesting a beneficial effect.

Autoimmune rheumatic diseases in women with coronary microvascular dysfunction: a report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project.

While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Apnea-Hypopnea Index an indicator of increased right cardiac preassures

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Obstructive sleep apnea (OSA) is a disorder frequently associated with clinical conditions and complications such as refractory hypertension, atrial fibrillation, nocturnal angina, dysrhythmias, congestive heart failure and stroke. Polysomnography is the gold standard test required to diagnose OSA, along with a targeted history and comprehensive examination of the patient. It involves the recording of various physiologic variables during sleep. Sleep related obstructive events may be measured using two indices: the apnea-hypopnea index (AHI) and the respiratory disturbance index, an AHI≥15 being diagnostic for OSA. The aim of this study was to determine the interaction between sleep apnea and demographic or echocardiographic markers. Material and methods This was a prospective study that included 33 patients with sleep apnea. Polysomnography was performed using a VitalNight cardiorespiratory polygraph to determine the apnea hypopnea index (AHI) and echocardiography was performed using a Vivid E95 scanner to determine the left ventricular ejection fraction (LVEF), the peak systolic right ventricular to right atrial pressure gradient (Gmax) and the right ventricular diameter and function (TAPSE and s’). Results The mean age of the patients was of 63±8 years and 14 patients (42%) had a Gmax>25mmHg. Regarding cardiovascular risk factors, 31 patients (94%) had arterial hypertension and 26 (79%) were smokers. Out of all patients, 25 (76%) had an appropriate echocardiographic acoustic window. The patients had mean values of AHI of 45±19. Mean values for the LVEF, Gmax, TAPSE and s’ were 53 ± 11%, 25± 14 m/s, 22 ± 4 mm, and 14 ± 3 cm/s, respectively. AHI showed moderate correlations to age (r=0.27), cervical perimeter (r=0.38) and BMI (r=0.30), but also to echocardiographic parameters as LVEF (r=0.29), Gmax (r=0.42), RV diameter (r=0.39), TAPSE (r=0.38) and s’ (r=0.34). ROC curves were determined to calculate the value of AHI to predict a Gmax >25 mmHg. A significant Gmax, as an indicator for increased right cardiac pressures, was predicted with a high sensitivity (86%) and specificity (84%) by a value of AHI > 45 (AUC=0.81, 95%CI = 0.64-0.927, p<0.001). Conclusion In conclusion the study demonstrated that smoking and hypertension are important risk factors in patients with sleep apnea syndrome. There was a significant correlation between AHI and echocardiographic parameters of the right heart. AHI can be used as a predictor of increased right cardiac preassure when the value is above 45.

Obstructive sleep apnea, myocardial perfusion and myocardial blood flow: A study of older male twins.

Obstructive sleep apnea (OSA) has been associated with incidence of cardiovascular disease and with nocturnal angina, but evidence of a link with coronary atherosclerosis and myocardial ischemia is limited and previous studies may have been affected by selection bias or unmeasured confounding factors. We performed overnight polysomnography in 178 older male twins. The Apnea/Hypopnea Index (AHI) was calculated to assess OSA from the overnight sleep evaluation. AHI ≥15 was used as indicator of moderate/severe OSA. The following day, twins underwent myocardial perfusion imaging with [82Rb]-chloride positron emission tomography. Quantitative and semiquantitative measures of myocardial perfusion and absolute myocardial blood flow were obtained. The mean age was 68 years and 40% of the sample had an AHI≥15, which indicates moderate to severe OSA. Abnormal myocardial perfusion, both with stress and at rest, was more common in twins with elevated AHI. After adjusting for clinical, lifestyle and behavioral factors, and previous history of cardiovascular disease, twins with AHI ≥15 had 3.6 higher odds (95% CI, 1.5-8.9) of an abnormal total severity score, defined as a score ≥100, and for each 5-point increment in AHI, the odds of abnormality increased by 20% (95% CI, 7%-34%). Twin pairs where both twins had OSA exhibited the greatest risk. There were no differences in measures of ischemia and absolute myocardial blood flow and flow reserve by AHI status. OSA is associated with myocardial perfusion abnormalities that suggest prior subclinical myocardial scarring or infarction. Early environmental factors that affect both twins equally may play a role and should be further explored.

Disfunción microvascular, angina vasoespástica e isquemia silente

Almost two thirds of patients with angina show no obstructive lesions on coronary angiography. It is important to rule out microvascular dysfunction or vasospastic angina in these patients. Microvascular dysfunction encompasses abnormalities in vessels smaller than 500μm. The capacity for correct vasodilation is lost and coronary flow cannot be increased in situations of stress causing ischaemia. In recent years, invasive diagnostic methods during catheterisation have been developed, the main method being coronary flow reserve. The aim of treatment is to improve endothelial function. ACE inhibitors/ARBs, beta-adrenergic-blocking drugs (BABs), and statins are recommended.Vasospastic angina is caused by vasoconstriction of the epicardial arteries or the arteries of microcirculation (microvascular dysfunction). It should be ruled out in patients with predominantly nocturnal rest angina. If suspected, provocation testing is indicated during catheterisation with acetylcholine, ergonovine or substance P. It responds to calcium antagonists and nitrates. ACE inhibitors and statins are also recommenced. BABs are contraindicated.Asymptomatic ischaemia is termed silent ischaemia. It is more frequent in diabetic patients. Diagnostic delay will determine prognosis.

Correlation between coronary artery disease and obstructive sleep apnea syndrome and analysis of risk factors.

The correlation between coronary artery disease (CAD) and obstructive sleep apnea syndrome (OSAS) was investigated to analyze its risk factors. A total of 84 patients with suspected CAD due to chest tightness and pain or nocturnal angina, were selected. They were admitted and received coronary angiography in The Affiliated Hospital of Medical College Qingdao University from March, 2016 to June, 2017. The vital signs were monitored, and the sleep monitoring was performed before and after coronary angiography. Before angiography, the fasting blood was drawn for blood biochemical detection, followed by routine electrocardiogram and echocardiographic examination. In addition, the body mass index was calculated and whether patients suffered from hypertension and diabetes mellitus was observed. The patients were divided into the control group (patients with a negative coronary angiography) and the CAD group (patients with a positive coronary angiography). There were 34 cases in the control group, including 21 cases of OSAS (61.76%), and 50 in the CAD group, including 40 cases of OSAS (80.00%). Statistical analysis revealed that there were statistically significant differences in the apnea hypopnea index (AHI), lowest oxygen saturation, degree of coronary stenosis (Gensini score) and triglyceride level between the two groups (P<0.05). There were no statistically significant differences in the cholesterol level and prevalence rates of hypertension and diabetes mellitus between the two groups. Logistic regression analysis revealed that smoking and AHI >20 were the risk factors of CAD (OR=7.036 and 5.377). Thus, CAD is closely correlated with OSAS and AHI >20 is one of the risk factors of CAD.

Presentation, Precipitants and Outcomes of Heart Failure and Preserved Ejection Fraction

Background: Although heart failure with preserved ejection fraction (HFpEF) is increasingly important, it has not been as well characterised as has heart failure with reduced ejection fraction (HFrEF). The aim of this study was to compare the precipitants, presenting symptoms, and outcomes of HFpEF versus HFrEF. We also investigated the long-term outcomes in response to medical therapy. Methods: We classified 5236 patients enrolled in the Management of Cardiac Failure (MACARF) program in Northern Sydney, into HFpEF (n = 1956, 37.3%) and HFrEF (n = 3280, 62.6%) patients using a cut-off left ventricular ejection fraction of 50%. Cox proportional hazards models were used for analysis of discharge medications. Results: Compared to HFrEF, the precipitant of hospitalisation for patients with HFpEF was more commonly infection (31.3% vs. 26.3%), and less likely to be ischaemia (18.7% vs. 23.3%). Although the predominant presenting symptom for all patients was dyspnoea, HFpEF patients were more likely to present with peripheral oedema (52.6% vs. 43.4%), whilst HFrEF patients were more likely to present with paroxysmal nocturnal dyspnoea, fatigue, weight gain, nausea and angina. Mortality rates at 30-days and 1-year were similar however HFpEF patients had higher 1-year readmission rates (45.4% vs. 40.7%) due to increased non-HF readmissions (34.7% vs. 29.8%). Adjusted hazard ratios showed improved survival for HFpEF patients discharged with beta blockers (HR 0.74; 95% CI: 0.60-0.88) and statins (HR 0.68; 95% CI: 0.53-0.88). Conclusion: Our study provides insight into differences between heart failure patients with preserved and reduced ejection fraction, and provides clues for prevention of hospitalisation and improved outcome.

Current and future developments in the field of central sleep apnoea.

Central sleep apnoea (CSA) occurs in ∼30-50% of patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and in as much as in 18-30% of patients with preserved LVEF. In HF patients, it is characterized by periodic breathing also known as the Cheyne-Stokes respiration followed by pauses of breathing. Central sleep apnoea remains often unrecognized due to its chronic and insidious incidences. Patients may report excessive daytime somnolence, poor sleep quality, nocturnal angina, recurrent arrhythmias, refractory HF symptoms, or demonstrate abnormal respiratory pattern or apnoeas. The pathogenesis of CSA remains incompletely understood, but changes in CO2 above and below the apnoea threshold play a major role in its pathogenesis. The presence of CSA in patients with HF is associated with some neurohumoral and haemodynamic responses that are detrimental to the failing heart including increased morbidity and mortality. The development of successful therapies targeting CSA and its harmful downstream effects is therefore important. Several different therapies from medications to implantable devices have been tested with varying effects and primarily in small non-randomized and/or single-centre studies. Large studies to date have been disappointing, but therapeutic options targeting the physiology of the disease may herald a new era in understanding and treating CSA.

Sleep, Death and the Heart

Normal sleep is associated with state changes in heart rate, blood pressure and neural circulatory control. During slow wave sleep, heart rate, blood pressure and sympathetic activity decrease whereas during REM sleep, sympathetic traffic to blood vessels increases significantly and heart rate and blood pressure are very labile. While these changes are physiologic, they may have implications for ischemia and arrhythmias in people with an underlying vulnerable substrate. While the overall decline in blood pressure during sleep is physiologic, subjects in whom the blood pressure decline is blunted or absent (non-dippers) are often at higher risk for cardiac and vascular events. Conversely, excessive nocturnal blood pressure decline has also been associated with cardiovascular risk including development of lacunar infarction. REM sleep has been linked to significant arrhythmias including asystole. REM has also been associated with coronary vasospasm and with angina (with ST depression) that causes waking from sleep. REM may also contribute to arrhythmogenesis in patients with ion-channelopathies. Indeed in patients with Long QT2 and Long QT3 syndromes, there is a markedly increased risk of fatal arrhythmic events occurring during sleep. Patients with Brugada syndrome also have a high risk of sleep-related sudden death. Interestingly these patients may have a higher than expected prevalence of obstructive sleep apnea. Disturbed sleep may also predispose to cardiac ischemia, arrhythmias and death. Obstructive sleep apnea (OSA) has been implicated in nocturnal angina and in myocardial infarction presenting during the nighttime hours. Apneic episodes have also been linked to bradyarrhythmias, including cardiac asystole. OSA patients have a higher risk of experiencing sudden death at night, and of receiving nighttime shocks from implanted defibrillators.

When to Suspect Sleep Apnea and What to Do About It

Obstructive sleep apnea (OSA), which is characterized by recurrent upper airway obstruction during sleep with resultant hypoxia-reoxygenation and sleep fragmentation, is prevalent among patients with cardiovascular disease. Refractory hypertension, nocturnal angina or arrhythmias, and stroke in particular should prompt consideration of OSA. The symptoms of OSA include snoring and excessive daytime sleepiness; risk factors include obesity and reduced upper airway dimensions. Up to 50% of patients with congestive heart failure (CHF) may manifest OSA, central sleep apnea-Cheyne-Stokes respiration (CSA-CSR), or both. Patients with CSA-CSR may present with fatigue, disrupted sleep, and paroxysmal nocturnal dyspnea. Objective sleep recording is required to document the nature and severity of sleep apnea. The gold standard is in-laboratory overnight polysomnography (PSG), including monitoring of electroencephalography and other signals to determine sleep-wake state, and recording of body position, airflow, respiratory effort, and pulse oximetry. Portable cardiorespiratory recorders are now approved for diagnosis in patients without comorbidities. Full PSG is recommended for diagnosis in all other cases, although OSA and CSA-CSR can be identified from portable recorders in some patients with CHF and other conditions. The objectives of treatment are to improve symptoms, quality of life, and cardiovascular outcomes. The mainstay of treatment for moderate-to-severe OSA is positive airway pressure (PAP). Automated PAP devices may be used in uncomplicated OSA, whereas continuous fixed PAP is the treatment of choice for other patients with OSA, and may also treat a proportion of patients with CSA-CSR. A form of bi-level PAP known as adaptive servoventilation is effective in treating a majority of patients with CSA-CSR.

Polymeric Drug Delivery Approaches for Colon Targeting: A Review

Colorectal cancer being a life style disease, number of cases is increasing day by day. Oral drug delivery to treat colonic diseases encounters many problems like drug stability in the harsh environment of the upper GI tract, low percentage of drug remained in the dosage form to be released in the colon, heavy dilution of the drug released in the colon fluid etc. Hence novel strategies for colon targeting has attracted significant attention during the past 20 years in providing several therapeutic advantages particularly for drugs that are sensitive to acidic condition and to intestinal enzymes. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis while site specific release strategy is needed for local action for conditions involving colonic pathologies, such as ulcerative colitis, colorectal cancer, Crohn's disease and colon cancer. This article is focused on different polymeric materials particularly of natural origin that are considered to design different types of colon delivery systems and their comparative efficacies are discussed. Keywords: Colon cancer, colon targeting, colon delivery of drugs, natural polymers.

Typical angina without significant coronary stenosis

The spectrum of patients with 'angina and normal coronary arteries' ranges from severe vasospasm to atypical chest pain. Among those with typical angina, however, little is known about similarities in the clinical profile and circadian presentation between typical nonvasospastic angina and normal coronary arteries (tANCA) and vasospastic angina (VA). Clinical, ECG, and angiographic features as well as the circadian characteristics of angina were compared between 384 tANCA and 273 VA patients. Follow-up events were also analyzed. tANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524). Despite differences in the clinical profile between VA and tANCA patients, there is notable sharing of circadian presentation of rest angina, response to nitroglycerin, and long-term presence and frequency of angina that suggests more similarities in underlying mechanisms than heretofore suspected.

Sudden cardiac arrest and syncope triggered by coronary spasm

BackgroundPatients with coronary spasm generally have a good prognosis, although it can result in sudden cardiac arrest (SCA) and syncope. We hypothesized that the nature of coronary spasm triggering lethal arrhythmias may be different from that which induces angina-only. MethodsClinical characteristics were examined in patients who had experienced SCA (n=18) or syncope (n=28) triggered by coronary spasm. These characteristics were compared to those of patients who had coronary spastic angina-only (n=52). ResultsSCA and syncope occurred frequently during daytime in 57% and 68%, respectively. Spontaneous ST-segment changes during daytime were recorded more often in patients with SCA (50%) and syncope (39%) than angina-only patients (4%, p<0.01 for each). Nocturnal angina occurred less frequently in patients with SCA (33%) and syncope (32%) than angina-only patients (83%, p<0.01 for each). Severe multivessel spasm, daytime ST-segment changes, and younger age were significant predictors of SCA. Daytime ST-segment changes and active smoking were related to syncope. ConclusionsThe circadian variance of coronary spasm triggering SCA or syncope may be different from that inducing typical coronary spastic angina. The coronary spasm should be evaluated for patients with aborted SCA or recurrent syncope of unknown cause, even though the patients have not experienced the typical nocturnal angina.

82-Year-Old Man With Bilateral Leg Swelling

An 82-year-old man with a medical history remarkable for chronic heart failure, diabetes mellitus, benign prostatic hyperplasia (BPH), and degenerative joint disease presented to the outpatient clinic with bilateral lower extremity swelling of 1 month's duration. The lower extremity edema was bilateral but slightly worse on the right. The edema worsened during the day but transiently improved when the patient was in the supine position. He had no symptoms of paroxysmal nocturnal dyspnea, angina, or orthopnea. He denied prolonged immobility and had no history of deep venous thrombosis (DVT). He had a history of myocardial infarction 20 years previously with resulting chronic heart failure. Of note, he had no known history of kidney or liver disease and had no remote or recent history of smoking. He denied a history of cancer or recent surgeries.

Clinical Risk Stratification in the Emergency Department Predicts Long-Term Cardiovascular Outcomes in a Population-Based Cohort Presenting With Acute Chest Pain

The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years.The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk.In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy.

Angina pectoris bei Koronaranomalie

Nocturnal angina occurred in a 43-year-old man. Biplane left-ventricular angiography demonstrated normal left ventricular function (ejection fraction of 75%) with mild apical hypokinesia. The right coronary artery had a normal origin, was dominant and its lumen smooth. The left coronary artery also originated from the right coronary cusp, the left main stem coursing between the pulmonary artery and aorta within the aortic wall. It had a long, 40% stenosis. During atrial stimulation (130 beats/min) angiography demonstrated a 60% increase in luminal narrowing. Because of the symptoms caused by the stenosis in the anomalous coronary artery a mammary artery implant into the anterior interventricular branch and a vein graft to the circumflex artery were performed. The patient has since been free of symptoms. In relatively young persons the presence of coronary artery anomalies should be considered in the differential diagnosis even of atypical chest pain; indications for cardiac catheterization with angiography should be broad.

Cardiovascular Manifestations Seen in Obstructive Sleep Apnea

Patients with obstructive sleep apnea (OSA) have an increased prevalence of systemic and pulmonary hypertension, left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunction, and congestive heart failure, increased platelet aggregability, and increased susceptibility to thrombotic and embolic cardiac and cerebrovascular events. Patients with OSA have an increased prevalence of coronary artery disease, myocardial infarction, nocturnal angina, and myocardial ischemia, arrhythmias, and sudden cardiac death. Patients with OSA also have an increased prevalence of stroke. Treatment of OSA with continuous positive airway pressure improves cardiac efficiency in patients with heart failure, causes a reduction in the frequency of nocturnal ischemic ST-segment depression, relieves nocturnal angina, and causes a reduction in the occurrence of new cardiovascular events and an increase in the time to such events.

Coronary spasm reflects inputs from adjacent esophageal system

Mechanisms underlying coronary spasm are still poorly understood. The aim of the study was to assess the hypothesis that fluctuations in the development of coronary spasm might reflect inputs from the adjacent esophageal system. We enrolled patients admitted to the coronary care unit for episodes of nocturnal angina. Seven patients with variant angina and five with coronary artery disease (CAD) had concurrent ECG and esophageal manometric monitoring. ECG monitoring documented 28 episodes of ST elevation in variant angina patients and 16 episodes of ST depression in CAD patients. Manometric analysis showed that esophageal spasms resulted remarkably more frequently in variant angina patients (143 total spasms; individual range 9-31) than in CAD patients (20 total spasms; individual range 0-9; P < 0.01). Time series analysis was used to assess fluctuations in the occurrence of abnormal esophageal waves and its relationship with spontaneous episodes of ST shift. Episodes of esophageal spasm in CAD were sporadic (<1 in 30 min) and not related to ECG-recorded ischemia. In the variant angina group, esophageal spasms were time related to ischemia (>1 into 5 min before ECG-recorded ischemia) (P < 0.05). A bidirectional analysis of causal effects showed that the influence processes between esophageal and coronary spasms were mutual and reciprocal (transfer function model, P < 0.05) in variant angina. We concluded that in variant angina patients, episodes of esophageal spasms and myocardial ischemia influenced each other. Mechanisms that cause esophageal spasm can feed back to produce coronary spasm. Coronary spasm may feed forward to produce additional episodes of esophageal spasm.

Colon drug delivery

Oral drug delivery to the colon has attracted significant attention during the past 20 years. Colon targeting is recognised to have several therapeutic advantages, such as the oral delivery of drugs that are destroyed by the stomach acid and/or metabolised by pancreatic enzymes. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Local treatment of colonic pathologies, such as ulcerative colitis, colorectal cancer and Crohn’s disease, is more effective with the delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents requires smaller doses. This article aims to provide an insight into the design and manufacturing considerations, and an evaluation of colonic drug delivery systems in order to understand why there are still few delivery technologies that have reached the market, despite intensive research in this field. For this purpose, various approaches to colon-specific drug delivery are discussed.

Cardiac Troponin T in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with nocturnal angina and ST-segment depression, which are relieved by treatment with continuous positive airway pressure (CPAP). We tested the hypothesis that severe nocturnal hypoxia in patients with OSA causes myocyte necrosis as evidenced by increases in cardiac troponin T. Prospective cohort study. Cardiovascular physiology and sleep research laboratory. Fifteen male volunteers with coronary artery disease (CAD) and moderate or severe OSA (apnea-hypopnea index [AHI] > 15). Polysomnography and measurement of serum cardiac troponin T before sleep, after 4 h of untreated OSA, and in the morning after 4 h of treatment with CPAP. The mean AHI for the group was 41 (SD 16), and the mean oxygen saturation nadir during sleep was 83% (SD 8%). All measurements of cardiac troponin T were < 0.010 ng/mL. Despite the fact that some patients with OSA may experience nocturnal ischemia, this study shows that patients with severe OSA and coexisting CAD do not have nightly episodes of myocardial injury detectable by the current-generation cardiac troponin T assay.