Risk Of Long-term Adverse Events Research Articles

P-642 The effect of oral dydrogesterone (DYD) on the hypothalamic-pituitary-ovarian (HPO) axis (gonadotropin and sex-steroid levels) and ovulation inhibition: a double-blind, phase I, randomized-controlled, parallel-group trial

Abstract Study question What is the effect of oral dydrogesterone (three cycles daily 20mg/30mg) on pituitary, ovarian and adrenal hormones, ovulation inhibition and endometrium in healthy ovulatory women? Summary answer Daily oral dydrogesterone, 20mg or 30mg, suppresses LH and inhibits ovulation in 33% and 73% of subjects, respectively, while not reducing E2 and other hormones. What is known already Dydrogesterone, a stereoisomer of progesterone, has high oral bioavailability and has demonstrated clinical utility in several indications, including endometriosis and assisted reproduction technologies. Progestin primed ovarian stimulation (PPOS) provides a cost effective and convenient alternative to the GnRH antagonist protocol to suppress a premature LH surge during ovarian stimulation in preparation for frozen embryo transfer IVF. In PPOS, studies have shown that dydrogesterone provides a comparable number of mature oocytes as a standard GnRH antagonist. The effects of various formulations and routes of administration of different progestins on sex hormones and the HPO has not been determined across the indications. Study design, size, duration A single-centre, double-blind, randomised, multiple-dose, parallel-group study of two doses of oral dydrogesterone over three 28-day treatment cycles: dydrogesterone 30mg, 10mg in the morning, afternoon and evening; dydrogesterone 20mg, afternoon dose replaced with placebo. The primary efficacy outcome was the number of subjects with “no ovulation at all” (Hoogland and Skouby score [HSS] 1-4) or “ovulation without pregnancy risk” (HSS 5-6 with negative Landgren criterion) recorded in all treatment cycles. Participants/materials, setting, methods The study population was 44 healthy, pre-menopausal women aged 18–35 years, with proven pre-treatment ovulation. The inclusion/exclusion criteria were defined to reflect the intended target population and the general contraindications for hormonal preparations. The primary objective was to compare the effect of the two self-administered doses of dydrogesterone on ovarian follicular growth leading to ovulation and E2 suppression. Secondary objectives included effect on other HPO hormones, the endometrium, PK characteristics and safety. Main results and the role of chance The number of responders to ovulation inhibition was dose-dependent: DYD 30mg, 72.7%, 95% CI: 49.78–89.27%; DYD 20mg, 33.3%, 95% CI: 14.59–56.97%. Based on HSS and Landgren criteria, there was 42.4% and 15.15% ovulation with pregnancy risk with the 20mg and 30mg doses, respectively. Neither dose had any clinically relevant influence on the average E2 concentration or FSH, androstenedione, dehydroepiandrosterone sulphate, testosterone and sex hormone binding globulin levels, while both doses suppressed the pre-ovulatory LH surge. Endometrial proliferation was mildly suppressed to a comparable extent with both daily doses. Hyperechogenic endometrium pattern was observed in 50% and 72% of treatment cycles in ovulating women in the 20mg and 30mg groups, respectively. Treatment with DYD did not significantly delay follicular growth or postpone ovulation in ovulating women. The more pronounced progesterone suppression with the higher 30mg dose may be due to the higher number of subjects without ovulation and thus without a post-ovulatory progesterone rise in that group. Return of ovulation after treatment cessation occurred in 91% women in the 42-day post-treatment period. The most frequently reported TEAE was ‘ovarian cyst’; all cases were of mild intensity and resolved at the end of the trial. No severe TEAE was reported. Limitations, reasons for caution Only two doses were studied in healthy, ovulatory women. DYD is used in various clinical contexts with concomitant other medications, such as gonadotropins for ovarian stimulation, or under luteotropic circumstances with human chorionic gonadotropin activity from exogenous or endogenous sources. Only limited morning PK sampling was performed. Wider implications of the findings Oral dydrogesterone used for endometriosis symptom reduction may be associated with a low risk of long-term adverse events from hypoestrogenism and suppression of androgens. Oral dydrogesterone displays relevant and short-term effects on LH levels, supporting its use in PPOS protocols. At therapeutic doses, dydrogesterone does not completely inhibit ovulation. Trial registration number EudraCT-No.: 2021-004747-24

Intramuscular methylprednisolone administration in hand osteoarthritis patients: a feasibility study to inform a randomized controlled trial.

Inflammation is thought to play an important role in hand osteoarthritis (HOA), which is associated with pain and increased limitation of hand function. To explore the acceptability of therapy with intramuscular methylprednisolone in HOA among health-care providers (HCPs) and HOA patients. Additionally, the response to a single methylprednisolone injection was investigated. We adopted a mixed-methods design. In a qualitative study, we asked HCPs and patients for their acceptability of intramuscular methylprednisolone. A prospective observational study was performed afterward in HOA patients who received a single 120-mg intramuscular methylprednisolone injection as part of off-label administration. Average pain, functional impairment, and occurrence of adverse events were assessed at baseline and at 4, 8, and 12 weeks after the injection. Fourteen HCPs and 15 patients participated in the first part of the study. They considered intramuscular methylprednisolone potentially effective, yet expressed concerns about the risk for long-term adverse events. Among the 22 HOA patients who received intramuscular methylprednisolone, 13 patients reported 44 adverse events, with half of them occurring within the first 4 weeks after injection and being classified as nonserious. Mean hand pain decreased the most 4 weeks after injection and this effect persisted till week 12, though less pronounced. Similar results were seen with HOA-related functional impairment, which improved the most at week 4 and to a lesser extent at week 12. We found a good acceptability of intramuscular methylprednisolone treatment among HCPs and HOA patients, as well as a potential to reduce pain and improve hand function with a good safety profile for as long as 12 weeks after a single administration.

Arterial hypertension in patients with takotsubo syndrome: prevalence, long-term outcome, and secondary preventive strategies: a report from the Takotsubo Italian Network register.

The aim of this study was to investigate the long-term outcome of takotsubo syndrome (TTS) patients with and without hypertension (HT) and to evaluate the effectiveness of treatment with beta-blockers (BBs) and/or renin-angiotensin-aldosterone system inhibitors (RAASi). The study population includes a register-based, multicentre cohort of consecutive patients with TTS, divided into two groups according to the history of HT. Further stratification was performed for BB/RAASi prescription at discharge. The primary outcome was the composite of all-cause death and TTS recurrence at the longest available follow-up. The propensity score weighting technique was used to account for potential confounding. In the overall population (903 patients, mean age 70 ± 11 years), HT was reported in 66% of cases. At a median 2-year follow-up, there was no difference in the risk of the primary composite outcome between patients with and without HT. The adjusted Cox regression analysis showed a significantly lower risk for the primary outcome [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.49-0.99] in patients who received BB vs. those who did not. Renin-angiotensin-aldosterone system inhibitors treatment was not associated with the primary study outcome. The lower risk for the primary outcome with BB treatment was confirmed in patients with HT (aHR: 0.37; 95% CI: 0.24-0.56) but not in patients without (aHR: 1.83; 95% CI: 0.92-3.64; Pinteraction < 0.001). In this TTS study, HT did not affect the long-term risk of adverse events but increased the probability of benefit from BB treatment after discharge. Owing to the favourable outcome impact of BB prescription in TTS patients with HT, a tailored pharmacological therapy should be considered in this cohort.

Moving toward Precision Medicine in Acute Coronary Syndromes: A Multimodal Assessment of Non-Culprit Lesions.

Patients with acute coronary syndrome and multivessel disease experience several recurrent adverse events that lead to poor outcomes. Given the complexity of treating these patients, and the extremely high risk of long-term adverse events, the assessment of non-culprit lesions becomes crucial. Recently, two trials have shown a possible clinical benefit into treat non-culprit lesions using a fraction flow reserve (FFR)-guided approach, compared to culprit-lesion-only PCI. However, the most recent FLOW Evaluation to Guide Revascularization in Multivessel ST-elevation Myocardial Infarction (FLOWER-MI) trial did not show a benefit of the use of FFR-guided PCI compared to an angiography-guided approach. Otherwise, intracoronary imaging using optical coherence tomography (OCT), intravascular ultrasound (IVUS), or near-infrared spectroscopy (NIRS) could provide both quantitative and qualitative assessments of non-culprit lesions. Different studies have shown how the characterization of coronary lesions with intracoronary imaging could lead to clinical benefits in these peculiar group of patients. Moreover, non-invasive evaluations of NCLs have begun to take ground in this context, but more insights through adequately powered and designed studies are needed. The aim of this review is to outline the available techniques, both invasive and non-invasive, for the assessment of multivessel disease in patients with STEMI, and to provide a systematic guidance on the assessment and approach to these patients.

The impact of pharmacist intervention on the intravenous-to-oral switch therapy of proton pump inhibitors in cardiovascular surgery

ABSTRACT Background The prescriptions of proton pump inhibitors (PPIs) have been widely concerned due to both huge increase in medical costs and possible long-term adverse events (AEs) caused by the improper route of drug administration. The aim of this study was to assess the effectiveness of pharmacist interventions on the clinical outcome and safety of switching from intravenous (IV) to oral PPIs therapy. Patients and methods A retrospective, single-center, pre- intervention (early -stage)- and intervention (later -stage) study was performed in a Chinese hospital. Results A total of 1736 patients were included in the study. After 12 months of interventions, significant improvements in the number of rational IV to oral switch in patients with oral switch indications were found. The median duration of oral therapy was increased, while the duration of PPIs therapy was decreased. Pharmacist interventions led to significant reductions in mean PPI costs, mean total drug costs, mean hospitalization costs, and the risk for long-term adverse events. Conclusion This study provides important evidence on the beneficial effect of pharmacist interventions on promoting an optimal IV to oral switch of PPIs and substantial cost saving by shortening the duration of IV PPIs therapy and reducing the risk for long-term AEs.

Impact of Clinical Presentation on Outcomes After Rotational Atherectomy in Patients Who Underwent Percutaneous Coronary Intervention

Rotational atherectomy (RA) is widely used in the percutaneous treatment of heavily calcified coronary artery lesions in patients with chronic coronary syndromes (CCS). However, the safety and efficacy of RA in acute coronary syndrome (ACS) is not well established and is considered a relative contraindication. Therefore, we sought to evaluate the efficacy and safety of RA in patients presenting with non-ST-elevation myocardial infarction (NSTEMI), unstable angina (UA), and CCS. Consecutive patients who underwent percutaneous coronary intervention with RA between 2012 and 2019 at a tertiary single center were included. Patients presenting with ST-elevation myocardial infarction (MI) were excluded. The primary end points of interest were procedural success and procedural complications. The secondary end point was the risk of death or MI at 1year. A total of 2,122 patients who underwent RA were included, of whom 1,271 presented with a CCS (59.9%), 632 presented with UA (29.8%), and 219 presented with NSTEMI (10.3%). Although an increased rate of slow-flow/no-reflow was noted in the UA population (p=0.03), no significant difference in procedural success or procedural complications, including coronary dissection, perforation, or side-branch closure, was noted (p=NS). At 1year, there were no significant differences in death or MI between CCS and non-ST-elevation ACS (NSTE-ACS: UA+NSTEMI; adjusted hazard ratio 1.39, 95% confidence interval 0.91 to 2.12); however, patients who presented with NSTEMI had a higher risk of death or MI than CCS (adjusted hazard ratio 1.79, 95% confidence interval 1.01 to 3.17). Use of RA in NSTE-ACS was associated with similar procedural success without an increased risk of procedural complications compared with patients with CCS. Although patients presenting with NSTEMI remained at higher risk of long-term adverse events, RA appears to be safe and feasible in patients with heavily calcified coronary lesions presenting with NSTE-ACS.

Risk Prediction Models for Ischemic Cardiovascular Outcomes in Patients with Acute Coronary Syndrome.

Acute coronary syndrome (ACS) has a high incidence of adverse cardiovascular events, even after early invasive treatment. Patients may still have a poor prognosis after discharge. The keys to the long-term survival of patients with ACS include effective treatment in a timely manner and identification of those patients who are at higher risk for long-term adverse events. Therefore, several nations have now devised a range of risk assessment models to provide data for accurately formulating treatment plans for patients with various risk levels following an ACS to prevent short and long-term cardiovascular events. The purpose of this article is to review the risk scores associated with mortality and ischemic events in patients with ACS. By using the clinical risk prediction score, we can accurately and effectively judge the prognosis of patients, so as to take a more reasonable treatment.

Predictors of Long-Term Outcomes after Surgical Myocardial Revascularization

High mortality from cardiovascular diseases (CVD) requires improved approaches to the treatment of this socially significant pathology. Wide implementation of surgical myocardial revascularization makes it possible to improve significantly both life quality and expectancy in patients with coronary heart disease. The aim of this work was to analyze the literature on the impact of preoperative, operative and postoperative factors on the long-term prognosis after coronary artery bypass grafting (CABG). The review refers to both recent and earlier informative works. The target groups for this article are therapists, cardiologists, rehabilitologists, who work with patients in the short and long term after CABG. Data of Russian and foreign literature show that the long-term prognosis after CABG is largely determined by preoperative factors, in particular – age, set of cardiovascular risk factors (RF) and comorbidity, specifically – severity of coronary and systemic atherosclerosis, incident cardiovascular complications, structural and functional state of the heart. In the aggregate these factors reflect the cumulative effect and further potential of actual cardiovascular RFs, affect longterm risk of adverse events, and determine the therapeutic targets of secondary prevention. Priority of arterial conduits and completeness of revascularization are the main operative factors that determine the course of the long-term period after CABG. Among the postoperative factors, the efficiency of secondary CVD prevention is of paramount importance, in particular – achievement of target RF levels, compensation of cardiac and extracardiac pathology, adherence to the long-term medical therapy, known to improve outcomes based on specific comorbidity. Efficiency of secondary CVD prevention largely depends on patient's health attitudes, the key influence on which beyond attending physician can be provided by participation in rehabilitation programs, teaching patients the meaning and essentials of lifestyle modification and cardiovascular RFs’ control.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Abstract Background There is a positive continuous association between Lipoprotein(a) (Lp[a]) levels and the risk of recurrent ischemic events in patients with recent myocardial infarction (MI). However, the prognostic significance of the association between high Lp(a) levels and diabetes has been poorly investigated after MI. Purpose The aim of this study was to evaluate the association of Lp(a) levels with the long-term risk of adverse events in post-MI patients, and to investigate whether diabetes may influence this association. Methods Consecutive MI patients who underwent urgent/emergent coronary angiography at our Institution from February 2013 to June 2019 were prospectively collected. Lp(a) serum concentrations was expressed for increasing range values (≤10, &amp;gt;10–30, &amp;gt;30–50, &amp;gt;50–70, and ≥70 mg/dL). The primary outcome was the recurrence of MI; the secondary outcome was all-cause death. The propensity score weighting technique was used to account for potential confounding between patients with and without diabetes. Results The study population consisted of 1018 post-MI patients (median age: 63 years; 76% males). Diabetes was reported in 280 patients (27.5%). The median value of Lp(a) was 10 mg/dL, and patients with diabetes showed significantly lower Lp(a) levels than patients without diabetes (p=0.025). At a median follow-up of 1121 days, the primary outcome was reported in 109 patients (10.7%), and the secondary outcome in 100 (9.8%). After propensity score weighting, there was a significant association between increasing Lp(a) range values and the primary outcome both in the overall population (p trend = 0.030) and in non-diabetic patients (p trend = 0.009), but not in diabetics. Conversely, no significant association with the risk of all-cause mortality across increasing Lp(a) categories both in the overall population and in the study groups according to the presence or not of diabetes was found. Compared with the lowest Lp(a) category, Lp(a) plasma levels &amp;gt;70 mg/dL were independently associated with the risk of recurrent MI (HR: 3.222; 95% CI, 1.225–8.478, p=0.018) and all-cause death (HR: 2.656; 95% CI, 1.009–6.991, p=0.048) in non-diabetic patients, but not in diabetics. Conclusions In this real-world post-MI population, Lp(a) serum levels were lower in diabetic than in non-diabetic patients. Increasing Lp(a) levels were significantly associated with the risk of recurrent MI, and very high Lp(a) serum concentration (&amp;gt;70 mg/dL) independently predicted recurrent MI and death in non-diabetic patients, but not in diabetics. These results reinforce the importance of routine assessment of Lp(a) levels after MI, particularly in patients without diabetes. Funding Acknowledgement Type of funding sources: None.

Machine learning in predicting immediate and long-term outcomes of myocardial revascularization: a systematic review

Machine learning (ML) is among the main tools of artificial intelligence and are increasingly used in population and clinical cardiology to stratify cardiovascular risk. The systematic review presents an analysis of literature on using various ML methods (artificial neural networks, random forest, stochastic gradient boosting, support vector machines, etc.) to develop predictive models determining the immediate and long-term risk of adverse events after coronary artery bypass grafting and percutaneous coronary intervention. Most of the research on this issue is focused on creation of novel forecast models with a higher predictive value. It is emphasized that the improvement of modeling technologies and the development of clinical decision support systems is one of the most promising areas of digitalizing healthcare that are in demand in everyday professional activities.

Pre-procedural ATI score (age-thrombus burden-index of microcirculatory resistance) predicts long-term clinical outcomes in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention

BackgroundThe ATI (Age-Thrombus burden-Index of Microvascular Resistance [IMR]) score was developed to predict suboptimal myocardial reperfusion in patients with ST-Elevation Myocardial Infarction (STEMI). When applied in the early phases of revascularization (e.g. before stent insertion), it predicts which patients are most likely to have a larger infarct size. In this study, we assessed the score's utility in determining which STEMI patients are at highest risk of clinical events during follow-up. MethodsThe ATI-score was calculated prospectively in 254 STEMI patients using age (>50 years = 1 point), pre-stenting IMR (>40 U and < 100 U = 1 point; ≥100 U = 2 points) and angiographic thrombus score (4 = 1 point, 5 = 3 points); the cohort was stratified in high vs. low-intermediate ATI-score strata (≥4 vs. < 4, respectively). ResultsAfter 3 years of follow-up, patients with high ATI-score presented a higher rate of Major Adverse Cardiac Events (MACE) defined as the composite of all-cause mortality, resuscitated cardiac arrest and new heart failure diagnosis (Hazard Ratio [HR]: 3.07; 95% Confidence Interval [CI]: 1.19–7.93; p = 0.02). The ATI-score showed a moderate discriminative power (c-stat: 0.69), not significantly different from that of other risk scores used in the STEMI setting. A high ATI-score was an independent predictor of MACE (HR: 3.24; 95% CI: 1.22–8.58; p = 0.018). ConclusionsThe ATI-score can discriminate patients at higher risk of long-term adverse events. The score allows predication of subsequent events even before coronary stenting, and consequently it may allow the option of individualized therapy in the early stages of the clinical care-pathway.

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs. ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.

Safety and Efficacy of Tattoo Removal Using a Dual-Wavelength 1064/532-nm Picosecond Laser in Patients With Fitzpatrick Skin Type III and IV.

To investigate the safety and efficacy of a dual-wavelength 1064/532-nm picosecond-domain laser for tattoo removal in Vietnamese patients. This prospective clinical study enrolled 30 subjects with 52 decorative tattoos treated with up to six treatments of laser removal at intervals of 6-8 weeks. Safety and efficacy were assessed at each treatment session and at 4 weeks after the final session. A "good" response was defined as at least 75% clearance of tattoo pigments. A significant reduction of tattoo appearance was achieved in all subjects. 88.5% of tattoos exhibited a "good" response to treatment by the end of the six sessions and more than 36% of tattoos exhibited better than "good" responses. Adverse events were common in the early period after treatment but did not persist in most patients. Only one case of prolonged hypopigmentation was reported. Treatment using a 1064/532-nm picosecond laser is an effective approach for removal of decorative tattoos, which poses a minimal risk of long-term adverse events in patients with Fitzpatrick skin type III or IV. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Peripheral Artery Disease Patients With Chronic Limb-Threatening Ischemia Show Altered Blood Microbiota Composition as Compared with Intermittent Claudication

Chronic limb-threatening ischemia (CLTI) is a severe manifestation of peripheral artery disease (PAD) with high morbidity for aging populations. While metabolites produced by the intestinal microbiota have been shown to predict long-term risk of adverse events in PAD patients, the contribution of the blood microbiota to the development of CLTI has not been investigated. We sought to profile the blood microbiota of PAD patients with CLTI as compared with intermittent claudication (CLAUD) to identify differences in microbial composition.

Post-contrast acute kidney injury in a hospitalized population: short-, mid-, and long-term outcome and risk factors for adverse events

ObjectivesTo investigate the prognosis including major adverse kidney events within 30 days (MAKE30) and 90-day and 1-year adverse outcome in hospitalized patients with post-contrast acute kidney injury (PC-AKI) to identify high-risk factors.MethodsThis retrospective observational study included 288 PC-AKI patients selected from 277,898 patients admitted to hospitals from January 2015 to December 2015. PC-AKI was defined according to the 2018 guideline of European Society of Urogenital Radiology. Multivariable Cox regression and logistic regression analyses were used to analyze main outcome and risk factors.ResultsPC-AKI patients with AKI stage ≥ 2 had much higher incidence of MAKE30 than those with AKI stage 1 (RR = 7.027, 95% CI 4.918–10.039). Persistent renal dysfunction, heart failure, central nervous system failure, baseline eGFR < 60 mL/min/1.73 m2, oliguria or anuria, blood urea nitrogen ≥ 7.14 mmol/L, respiratory failure, and shock were independent risk factors of 90-day or 1-year adverse prognosis (p < 0.05). Compared with transient renal dysfunction, PC-AKI patients with persistent renal dysfunction had a higher all-cause mortality rate (RR = 3.768, 95% CI 1.612–8.810; RR = 4.106, 95% CI 1.765–9.551) as well as combined endpoints of death, chronic kidney disease, or end-stage renal disease (OR = 3.685, 95% CI 1.628–8.340; OR = 5.209, 95% CI 1.730–15.681) within 90 days or 1 year.ConclusionsPC-AKI is not always a transient, benign creatininopathy, but can result in adverse outcome. AKI stage is independently correlated to MAKE30 and persistent renal dysfunction may exaggerate the risk of long-term adverse events.Key Points• PC-AKI can result in adverse outcome such as persistent renal dysfunction, dialysis, chronic kidney disease (CKD), end-stage renal disease (ESRD), or death.• AKI stage is independently correlated to MAKE30.• Persistent renal dysfunction may exaggerate the risk of long-term adverse events.

Extreme ST-segment elevations in seemingly no significant angiographic coronary artery abnormalities: a case report

BackgroundObstructive coronary artery disease is found in approximately 97% of patients presenting with ST-elevation myocardial infarction and 92% of patients with non ST-elevation myocardial infarction (Bainey KR, Welsh RC, Alemayehu W, Westerhout CM, Traboulsi D, Anderson T, et al. Int J Cardiol 264: 12–17, 2018). Recent studies showed that myocardial infarction without obstructive coronary atherosclerosis (MINOCA) is also associated with a long-term risk of adverse events (Bainey KR, Welsh RC, Alemayehu W, Westerhout CM, Traboulsi D, Anderson T, et al. Int J Cardiol 264: 12–17, 2018).. The following case illustrates that MINOCA may also be associated with short term adverse events (depending on the underlying mechanism).Case presentationA 49-year old Caucasian male with no significant medical history was referred to our cardiac emergency department with acute chest pain. The ambulance ECG showed extreme ST-segment elevation anterolateral (‘tombstone sign’), which had resolved completely at arrival in the hospital. Coronary angiography showed no obstructive coronary artery disease. Conservative (medical) therapy was started and patient was discharged. Two days later he presented with recurrent cardiac ischemia with ventricular fibrillation. Coronary angiography showed no changes compared with earlier presentation. During admission to the ICU his clinical condition gradually deteriorated, eventually leading to his death. Post-mortem studies showed no significant atherosclerotic lesions. Massive myocardial infarction was found, probably caused by temporary occlusion of the left main coronary artery.ConclusionsSeveral pathophysiological mechanisms are recognized in MINOCA, of which vasospasm is the most probable one in this case. MINOCA is associated with increased over-all mortality and risk of ventricular arrhythmias. Therefore, additional testing should be considered when there is no explanation for the mismatch between ST-elevations (STEMI) and (no significant) coronary abnormalities.

Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort.

Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment. We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p<0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p<0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p<0·0001). Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population. National Cancer Institute and the American Lebanese-Syrian Associated Charities.

Relationship between intra-operative vein graft treatment with DuraGraft® or saline and clinical outcomes after coronary artery bypass grafting

ABSTRACTBackground: Saphenous vein grafts (SVGs) remain the most often used conduits for coronary bypass grafting (CABG). Progressive intimal hyperplasia contributes to vein-graft disease and vein-graft failure (VGF). We compared the impact of intraoperative preservation of SVGs in a storage solution (DuraGraft®) versus heparinized saline on VGF-related outcomes after CABG.Methods: From 1996 to 2004, 2436 patients underwent isolated CABG with ≥ 1 SVG. SVGs were consecutively treated with DuraGraft in 1036 patients (2001−2004) and heparinized saline in 1400 patients (1996−1999). Short- (< 30 days) and long-term (≥ 1000 days) outcomes were assessed using repeat revascularization (primary end point), and major adverse cardiac events (MACE) consisting of the composite of death, nonfatal myocardial infarction, or repeat revascularization.Results: Mean follow-up in the DuraGraft group was 8.5 ± 4.2 years and 9.9 ± 5.6 years in controls. Short-term event rates were low and generally did not differ between groups. DuraGraft was associated with a 45% lower occurrence of nonfatal myocardial infarction after 1000 days (hazard ratio 0.55, 95% CI 0.41−0.74; P < 0.0001). There was 35% and 19% lower long-term risk for revascularization (HR 0.65, 95% CI 0.44−0.97; P = 0.037) and MACE (HR 0.81, 95% CI 0.70−0.94; P = 0.0051), respectively, after DuraGraft. Mortality was comparable between both groups at 1, 5, and 10 years. There was no statistically significant association between DuraGraft exposure and time to death starting at 30 or 1000 days (HR 0.91, 95% CI 0.76−1.09; P = 0.29).Conclusion: In this study, intraoperative treatment of SVGs with DuraGraft was associated with a lower risk of long-term adverse events suggesting that efficient intraoperative SVG treatment may reduce VGF-related complications post-CABG. These data warrant randomized clinical trials to validate these findings.

Impact of major bleeding on the risk of acute kidney injury in patients undergoing off-pump coronary artery bypass grafting.

Patients with perioperative bleeding during cardiac surgery are susceptible to acute kidney injury (AKI) which is proposed to be associated with short-term and long-term risk of adverse events. The relationship between perioperative bleeding in off-pump coronary artery bypass grafting (OPCAB) and AKI remains unknown. The purpose of this study is to evaluate the impact of perioperative bleeding on the risk of postoperative AKI in patient undergoing OPCAB. Perioperative major bleeding was defined by the universal definition of perioperative bleeding (UDPB) class 3 to 4. The primary endpoint was postoperative AKI which was diagnosed using criteria of stage 1 of AKI proposed by Acute Kidney Injury Network (AKIN). The secondary endpoints included in-hospital mortality and the incidence of postoperative myocardial infarction (MI). Baseline characteristics were compared between patients with and without major bleeding. Multivariable logistic regression analysis was performed to identify potential predictive factors for AKI after OPCAB. A total of 4,030 ACS (acute coronary syndrome) patients who underwent OPCAB were included in this study. Major bleeding rate was 9.8% (n =394). AKI was found in 995 (24.7%) patients. Multivariable regression analysis showed that perioperative major bleeding conferred a significantly higher risk of AKI after OPCAB with an odds ratio of 1.67 (95% confidence interval 1.32-2.10, P<0.001). When a decrease in hemoglobin, transfusion and chest tube output were included in the same logistic model separately to replace major bleeding, transfusion was the most strongly risk factor associated with AKI after surgery (OR =2.08, 95% CI: 1.38-3.16, P<0.001). Perioperative bleeding is associated with a higher risk of postoperative AKI in ACS patients who underwent OPCAB. Moreover, blood and blood products transfusion most correlated with AKI after surgery. Prevention of severe bleeding and reducing blood transfusion requirement may improve the outcomes of OPCAB.

Long-term prognostic value of lowering in free triiodothyronine in patients with hypertrophic cardiomyopathy

Objective: To determine whether thyroid hormone (TH) level could also be an independent and incremental predictor of adverse events in patients with hypertrophic cardiomyopathy (HCM). Methods: A total of 982 consecutive patients with HCM at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013 were included in the present study, and followed up till the end of December 2016. The patients were divided into three groups according to the levels of free triiodothyronine (FT3): the group 1 (FT3≤4.28 pmol/L, n=335), the group 2 (FT3>4.28-<4.79 pmol/L, n=310), and the group 3 (FT3 4.79-6.30 pmol/L, n=337). Results: After a follow-up period of (53.8±14.1) months, 39 patients (4.0%) either suffered death with all causes or received a cardiac transplantation (7.8%, 2.9% and 1.2% of the patients in the group 1, group 2 and group 3, respectively). A multivariable Cox regression analysis revealed that FT3≤4.28 pmol/L was associated with a significantly higher risk of all-cause mortality or cardiac transplantation (HR 8.83, 95% CI 1.115- 69.905,P=0.039) in HCM patients. Conclusions: Low levels of FT3 is a risk factor of adverse events for patients with HCM, indicting a role of FT3 as a marker for assessing the risk of long-term adverse events in these patients.