Higher Risk Of Cardiac Events Research Articles

Association between B-lines on Lung Ultrasound, Invasive Hemodynamics and Prognosis in Acute Heart Failure Patients.

Increased left atrial pressure leads to pulmonary congestion. Although the B-lines in lung ultrasound (LUS) are useful in detecting pulmonary congestion, data regarding the association between B-lines and invasive hemodynamics are inconsistent. This study aimed to explore the correlation of the B-line count by LUS with pulmonary capillary wedge pressure (PCWP) stratified for preserved and reduced ejection fraction (EF) in acute heart failure patients. We performed a prospective observational study on 116 hospitalized patients with acute heart failure (mean age, 75.2 ± 10.3 years), who underwent right heart catheterization before discharge. LUS was performed in eight zones within 4 h of right heart catheterization and compared with PCWP separately in each EF group. Cardiac events were recorded 1 year after discharge. PCWP revealed a clear pivot point at which the B-lines began to increase in the overall cohort and each EF. Specific thresholds of the increase in B-lines were identified at 19 and 25 mmHg for preserved and reduced EF, respectively. Residual congestion at discharge was defined as the presence of ≥6 B-lines. Patients with residual congestion had a higher risk for cardiac events than those without residual congestion (hazard ratio, 12.6; 95% CI, 4.71-33.7; log-rank, P < 0.0001). A clear pivot point was associated with increased B-lines count in PCWP at 19 and 25 mmHg for preserved and reduced EF, respectively. Moreover, the increased B-line count above the defined cutoff used to quantify residual congestion was associated with significantly worse outcomes.

Association of the P441L KCNQ1 variant with severity of long QT syndrome and risk of cardiac events.

Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.

Risk stratification of perioperative myocardial infarction/injury following noncardiac surgery in high risk patients

Abstract Background Perioperative myocardial infarction/injury (PMI) screening is increasingly recommended by current guidelines. PMI is often caused by type 2 myocardial infarction, and risk stratification tools for these patients are lacking. Purpose To derive and internally validate a risk prognostication model for PMI of likely type 2 infarction (lT2MI) Methods We included consecutive high-risk patients undergoing noncardiac surgery into this prospective multicenter study. Patients received a systematic routine PMI screening with pre- and postoperative measurement of cardiac troponin (cTn). PMI was prospectively defined as an absolute increase of cTn above the preoperative value. PMI etiology was centrally adjudicated and hierarchically classified by 2 independent physicians based on all clinical information obtained during index hospitalization and selected those with lT2MI for further analyses. To identify risk factors and allow risk stratification in lT2MI, we prespecified that only perioperative variables should be included into the model. We constructed a logistic binary regression model for major adverse cardiac events (MACE) within 120 days, including variables available at time of clinical evaluation: additional symptoms or ECG-criteria required according to the Universal Definition of Myocardial Infarction, absolute increase in cTn (categorized according to level of absolute increase 1–&amp;lt;2 times the 99th percentile, ≥2 to &amp;lt;4 times, and ≥4 times), urgency of procedure, perioperative bleeding (drop in haemoglobin &amp;gt;30g/L or deemed relevant for PMI by adjudicator), and ESC/ESA surgery risk (low, medium, high risk of cardiac events). Variables were omitted from the final model if the p-value was &amp;gt;0.05. Variable levels with similar odds ratios were grouped for simplification of the prognostic model. We constructed a calibration plot and calculated the area under the receiver-operating characteristics curve (AUC) and Brier Score. For internal validation we calculated the predicted probabilities and classified patients into low-risk (predicted event rate &amp;lt;10%), intermediate range (10–20%), and high-risk (&amp;gt;20%), and compared the predicted with the observed event rate. Results PMI occurred in 1016/7754 patients (13.1%) of which 750/1016 (73.8%) were adjudicated as lT2MI. MACE within 120 days occurred in 118/750 (15.7%) patients. The initial and final logistic prognostic model for 120-day MACE or death is shown in the table. Internal validation found a good fit of predicted and observed event rate following bootstrapping of 1000 iterations (Figure 1), a good AUC of 0.71 and a Brier score of 0.12. Conclusion The derived risk prognostication model for PMI of lT2MI can aid in the stratification of patients and support clinical decision making following noncardiac surgery. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation

Time series clustering of left atrial strain curves for risk stratification in the general population

Abstract Objective Currently, only the peak reservoir left atrial (LA) strain has been in use while a huge amount of useful information during different phases of cardiac cycle has been ignored. In this study, therefore, we tested the hypothesis that an unsupervised time series analysis utilizing the whole LA deformation curves will identify distinct clusters associated to risk factors and improve cardiovascular (CV) risk prediction over the traditionally used covariables in the general population. Design and method We prospectively studied 929 community-dwelling individuals (mean age, 51.6 years; 52.9% women), in whom we acquired clinical and echocardiographic data including LA strain traces at baseline and collected cardiac events on average 7.2 years later. We employed two unsupervised time series techniques such as Self-Organizing map and Variational Autoencoder (VAE) with Convolutional Neural Network as building block to cluster spatiotemporal patterns of LA strain curves. Clinical characteristics and cardiac outcome were used to evaluate the validity of the clusters (k). Results According to the quantization error value for every k, the optimal number of clusters was 5 for applied methods. Figure 1 (left panel) illustrates the centroids of the clusters using the proposed VAE network. The first three clusters had differences in sex distribution and heart rate, but had similar low CV risk profiles. On the other hand, cluster 5 had the worst CV risk factors combination, and higher prevalence of left ventricular remodelling and diastolic dysfunction (ie, lowest e' velocity and highest E/e') compared to other clusters. We also observed an increase in the risk for incidence of adverse events between cluster 5 and other clusters (Figure 1, right panel). After adjustment for traditional risk factors, cluster 5 had the highest risk of cardiac events as compared to cluster 1, 2 and 3 (HR: 1.36; 95% CI: 1.10–1.69); P=0.0046). Conclusion Unsupervised Machine/Deep Learning algorithms employed on time series LA strain curves identifies clinically meaningful clusters of LA deformation, and provides incremental prognostic information over traditional risk stratification. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven

Usefulness of the pulmonary venous flow waveform for assessing left atrial stiffness.

This study investigated the novel non-invasive left atrial (LA) stiffness parameter using pulmonary venous (PV) flow measurements and the clinical usefulness of the novel LA stiffness parameter. We retrospectively analyzed 237 patients who underwent right heart catheterization and echocardiography less than one week apart. From the pulmonary artery wedge pressure waveform, the difference between x-descent and v-wave (ΔP) was measured. Using the echocardiographic biplane method of disks, the difference between LA maximum volume and that just before atrial contraction (ΔVMOD) was calculated, and the ΔP/ΔVMOD was calculated as a standard LA stiffness index. From the PV flow waveform, the peak systolic velocity (S), peak diastolic velocity (D), and minimum velocity between them (R) were measured, and S/D, S/R, and D/R were calculated. From the speckle tracking echocardiography-derived time-LA volume curve, the difference between LA maximum volume and that just before atrial contraction (ΔVSTE) was measured. Each patient's prognosis was investigated until threeyears after echocardiography. Among the PV flow parameters, D/R was significantly correlated with ΔP (r = 0.62), and the correlation coefficient exceeded that between S/D and ΔP (r = - 0.39) or S/R and ΔP (r = 0.14). The [D/R]/ΔVSTE was significantly correlated with ΔP/ΔVMOD (r = 0.61). During the follow-up, 37 (17%) composite endpoints occurred. Kaplan-Meier analysis showed that patients with [D/R]/ΔVSTE greater than 0.13 /mL were at higher risk of cardiac events. The [D/R]/ΔVSTE was useful for assessing LA stiffness non-invasively and might be valuable in the prognostic evaluation of patients with cardiac diseases.

Epidemiology of sudden cardiac death and sudden cardiac arrest with resultant disability during high school organized sport in Japan

ObjectivesTo examine the incidence and survival rates of sudden cardiac arrest that were documented during school organized sports in Japan. DesignRetrospective cohort study. MethodsInsurance claim data of cardiac events (sudden cardiac death and sudden cardiac arrest with resultant disabilities) that occurred during Japanese high school organized sports between 2009 and 2018 were retrieved. Participation data from All Japan High School Athletic Federation and Japan High School Baseball Federation were used for incidence rate calculations. Incidence rate ratios with 95 % confidence interval were calculated to compare the risk by sports and sex. The survival rate was calculated with the proportion of resuscitated cases to total number of cardiac events in this dataset. ResultsA total of 55 cardiac events (25 survivors and 30 deceased) were identified in the dataset. The majority affected male student-athletes (92.7 %). The frequency and incidence rate of cardiac events were highest in male baseball (n = 16 [29.1 %], incidence rate: 0.91 per 100,000 athlete-years). Incidence rate ratio revealed that male basketball (2.19, 95 % confidence interval: 1.04–4.60), male baseball (2.31, 95 % confidence interval: 1.32–4.03), and first-year male baseball (4.11, 95 % confidence interval: 2.10–8.07) had significantly higher risk of cardiac events, compared to the overall incidence rate (0.38 per 100,000 athlete-years). The survival rates were 37.5 % in the first half (2009–2013) and 56.5 % in the latter half (2014–2018) of the study period. ConclusionsThe risk of cardiac events was highest in male, baseball, first-year student-athletes. Rapid AED application by bystanders should be advocated to enhance better survival.

Type 1 Diabetes Mellitus and Premature Coronary Artery Disease

Cardiovascular disease, which affects more than half of all diabetics, is the leading cause of morbidity and mortality in patients with type 1 and type 2 Diabetes Mellitus (DM). Around 55% of diabetes patients are thought to have it, in comparison to 2-4% of the general population. A significant risk factor for the development of Coronary Artery Disease (CAD) exists in people with Type 1 Diabetes Mellitus (T1DM). However, it is worth noting that the present Models of risk prediction for T1DM have a variety of flaws. CAD risk is expected to double or quadruple over the next two to four decades, and diabetes mellitus is the third most significant risk factor for the etiology of illness. As a result, diabetes increases the chance of developing Acute Coronary Syndromes (ACS), whose incidence surpasses 20% after seven years, compared to a rate of 3.5 percent in non-diabetics – a rate comparable to individuals who have already experienced an Acute Myocardial Infarction (AMI). Additionally, it is crucial to identify any well-defined specific risk factors for T1DM as well as any extra subclinical atherosclerosis that may influence these patients at an advanced stage of disease progression. T1DM patients have more severe lesions, a lower left ventricle (LV) ejection fraction, a higher risk of cardiac events, and a higher rate of silent ischemia when compared to non-diabetics. They continue to have impaired microcirculation and endothelial function, both of which contribute to tissue perfusion problems.

TIME SERIES CLUSTERING OF LEFT ATRIAL STRAIN CURVES FOR RISK STRATIFICATION IN THE GENERAL POPULATION

Objective: Currently, only the peak reservoir left atrial (LA) strain has been in use while a huge amount of useful information during different phases of cardiac cycle has been ignored. In this study, therefore, we tested the hypothesis that an unsupervised time series analysis utilizing the whole LA deformation curves will identify distinct clusters associated to risk factors and improve cardiovascular (CV) risk prediction over the traditionally used covariables in the general population. Design and method: We prospectively studied 929 community-dwelling individuals (mean age, 51.6 years; 52.9% women), in whom we acquired clinical and echocardiographic data including LA strain traces at baseline and collected cardiac events on average 7.2 years later. We employed two unsupervised time series techniques such as Self-Organizing map and Variational Autoencoder with Convolutional Neural Network as building block to cluster spatiotemporal patterns of LA strain curves. Clinical characteristics and cardiac outcome were used to evaluate the validity of the clusters (k). Results: According to the quantization error value for every k, the optimal number of clusters was 5 for applied methods. Overall, both methods agreed with respect to cluster assignment. Figure (left panel) presents centroid LA strain curves which represent each cluster. The first three clusters had differences in sex distribution and heart rate, but had similar low CV risk profiles. On the other hand, cluster 5 had the worst CV risk factors combination, and higher prevalence of left ventricular remodelling and diastolic dysfunction (ie, lowest e’ velocity and highest E/e’) compared to other clusters. We also observed an increase in the risk for incidence of adverse events between cluster 5 and other clusters (Figure, right panel). After adjustment for traditional risk factors, cluster 5 had the highest risk of cardiac events as compared to cluster 1, 2 and 3 (HR: 1.34; 95%CI: 1.05–1.73); P = 0.020). Conclusions: Unsupervised Machine/Deep Learning algorithms employed on time series LA strain curves identifies clinically meaningful clusters of LA deformation, and provides incremental prognostic information over traditional risk stratification.

P140 EFFICACY AND SAFETY OF CHEMOTHERAPY CONTAINING NON–PEGYLATED LIPOSOMAL DOXORUBICIN IN PATIENTS AT HIGH CARDIOVASCULAR RISK: A SINGLE–CENTER EXPERIENCE

Abstract Anthracyclines represent the most effective chemotherapeutic agent in the treatment of non–Hodgkin‘s lymphoma (NHL), although their use is limited due to the risk of cardiac toxicity. This occurs mainly in elderly patients, those with a history of cardiovascular (CV) disease and/or multiple concomitant risk factors. Liposomal doxorubicin has been shown to reduce this toxicity. The aim of this retrospective study is to investigate the use of non–pegylated liposomal doxorubicin in high–risk patients in terms of haematological response rate and CV events. In a single centre, 15 patients undergoing R–COMP regimen (Rituximab, Prednisone, Cyclophosphamide, Vincristine, Myocet liposomal doxorubicin) were consecutively collected from January 2020 to December 2021. The mean age of patients was 73.9 years and 60% were male. The baseline mean left ventricular ejection fraction (LVEF) was 55.9%; four patients had a baseline FE of &amp;lt; 50%, two of them had a severe reduction in LVEF. Among all patients, 86.7% had systemic hypertension, 40% diabetes mellitus, 46.7% dyslipidaemia and 20% a family history of CV disease. Moreover, 46.7% of patients had at least two concomitant risk factors and 20% at least three. 20% had a history of ischemic heart disease, 13.3% had previous exposure to anthracyclines and 20% with mediastinal radiotherapy; 26.7% had moderate to severe aortic valvulopathy. According to the joint Cardio–Oncology evaluation, 100% of patients had been considered unsuitable for conventional doxorubicin.. More than 85% of the cases were already on cardioactive therapy at baseline evaluation and 66.7% required titration or modification during chemotherapy. With R–COMP, the whole population was able to finish treatment achieved complete haematological remission. The mean LVEF at the end of treatment was 55.8% (p = 0.814). Conclusions Our results support the efficacy and safety of R–COMP in a population at high risk for cardiac events, otherwise excluded from anthracycline–containing therapy. Liposomal formulatio reduces doxorubicin cardiomyocyte accumulation and thus toxicity, providing the best possible treatment for the majority of the onco–haematological population.

Improvement of Sympathovagal Balance by Regular Exercise May Counteract the Ageing Process. A Study by the Analysis of QT Variability.

QT interval (QT) variability analysis provides pathophysiological and prognostic information utilized in cardiac and non-cardiac diseases, complementary to those obtained from the analysis of heart period (HP) variability. An increased QT variability has been associated to a higher risk for cardiac events and poorest prognosis. Autonomic cardiovascular adaptation to internal and external challenges, such those occurring in athletes exposed to high levels of physical stress and in ageing could also be deepen by analyzing QT variability, searching for early prognostic signatures. The aim of the study was to analyze the QT variability and cardiac control complexity in a group of middle-aged half-marathon runners at baseline (B) and at a 10-year follow-up (FU). We found that the overall QT variability decreased at FU, despite the inescapable increase in age (52.3 ± 8.0 years at FU). This change was accompanied by an increase of the HP variability complexity without changes of the QT variability complexity. Of notice, over the years, the group of athletes maintained their regular physical activity by switching to a moderate intensity rather than strenuous. In conclusion, regular and moderate exercise over the years was beneficial for this group of athletes, as reflected by the decreased overall QT variability that is known to be associated to lower cardiovascular risk. The concomitant enhanced cardiac control complexity also suggests a trend opposite to what usually occurs with ageing, resulting in a more flexible cardiac control, typical of younger people.

Surgical Outcomes in Canada and the United States: An Analysis of the ACS-NSQIP Clinical Registry.

There has been longstanding uncertainty over whether lower healthcare spending in Canada might be associated with inferior outcomes for hospital-based care. We hypothesized that mortality and surgical complication rates would be higher for patients who underwent four common surgical procedures in Canada as compared to the US. We conducted a retrospective cohort study of all adults who underwent hip fracture repair, colectomy, pancreatectomy, or spine surgery in 96 Canadian and 585 US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) between January 1, 2015 and December 31, 2019. We compared patients with respect to demographic characteristics and comorbidity. We then compared unadjusted and adjusted outcomes within 30-days of surgery for patients in Canada and the US including: (1) Mortality; (2) A composite constituting 1-or-more of the following complications (cardiac arrest; myocardial infarction; pneumonia; renal failure/; return to operating room; surgical site infection; sepsis; unplanned intubation). Our hip fracture cohort consisted of 21,166 patients in Canada (22.3%) and 73,817 in the US (77.7%), for colectomy 21,279 patients in Canada (8.9%) and 218,307 (91.1%), for pancreatectomy 873 (7.8%) in Canada and 12,078 (92.2%) in the US, and for spine surgery 14,088 (5.3%) and 252,029 (94.7%). Patient sociodemographics and comorbidity were clinically similar between jurisdictions. In adjusted analyses odds of death was significantly higher in Canada for two procedures (colectomy (OR 1.22; 95% CI 1.044-1.424; P = .012) and pancreatectomy (OR 2.11; 95% CI 1.26-3.56; P = .005)) and similar for hip fracture and spine surgery. Odds of the composite outcome were significantly higher in Canada for all 4 procedures, largely driven by higher risk of cardiac events and post-operative infections. We found evidence of higher rates of mortality and surgical complications within 30-days of surgery for patients in Canada as compared to the US.

Genetic risk and its role in primary prevention of CAD

Coronary artery disease (CAD) is a pandemic disease and the number one cause of death in the world. Predisposition to CAD is about 50% acquired and 50% genetic. CAD prevention has been proven in randomized clinical trials with statin therapy. However, primary prevention is limited by the lack of biomarkers to detect asymptomatic young individuals at risk. Traditional risk factors (TRFs) such as hypertension or Type 2 Diabetes are age-dependent and often not present until the sixth or seventh decade. In contrast, genetic risk determined at conception is potentially a biomarker to detect young individuals at risk for CAD. The first genetic risk variant for CAD (9p21) was discovered in 2007, and subsequently, over 200 risk variants for CAD were discovered. A genetic risk score (GRS) based on the genetic risk variants for CAD was evaluated in over one million individuals. Retrospective analysis of clinical trials assessing the effect of statin therapy showed that individuals with the highest GRS had the highest risk for cardiac events and also the most benefit from lowering cholesterol. In a recent study of 55,685 individuals, those with the highest GRS (20%) had a 91% higher risk for cardiac events. Furthermore, those with high genetic risk on a favorable lifestyle had 46% fewer cardiac events than those with an unfavorable lifestyle. The GRS is superior and independent of TRFs. Incorporation into clinical practice will be a paradigm shift in preventing this pandemic.

Increased myocardial oxygen consumption rates are associated with maladaptive right ventricular remodeling and decreased event-free survival in heart failure patients

BackgroundReduced left ventricular (LV) function is associated with increased myocardial oxygen consumption rate (MVO2) and altered sympathetic activity, the role of which is not well described in right ventricular (RV) dysfunction. Methods and results33 patients with left heart failure were assessed for RV function/size using echocardiography. Positron emission tomography (PET) was used to measure 11C-acetate clearance rate (kmono), 11C-hydroxyephedrine (11C-HED) standardized uptake value (SUV), and retention rate. RV MVO2 was estimated from kmono. 11C-HED SUV and retention indicated sympathetic neuronal function. A composite clinical endpoint was defined as unplanned cardiac hospitalization within 5 years. Patients with (n = 10) or without (n = 23) RV dysfunction were comparable in terms of sex (male: 70.0 vs 69.5%), LV ejection fraction (39.6 ± 9.0 vs 38.6 ± 9.4%), and systemic hypertension (70.0 vs 78.3%). RV dysfunction patients were older (70.9 ± 13.5 vs 59.4 ± 11.5 years; P = .03) and had a higher prevalence of pulmonary hypertension (60.0% vs 13.0%; P = .01). RV dysfunction was associated with increased RV MVO2 (.106 ± .042 vs .068 ± .031 mL/min/g; P = .02) and decreased 11C-HED SUV and retention (6.05 ± .53 vs 7.40 ± 1.39 g/mL (P < .001) and .08 ± .02 vs .11 ± .03 mL/min/g (P < .001), respectively). Patients with an RV MVO2 above the median had a shorter event-free survival (hazard ratio = 5.47; P = .01). Patients who died within the 5-year follow-up period showed a trend (not statistically significant) for higher RV MVO2 (.120 ± .026 vs .074 ± .038 mL/min/g; P = .05). ConclusionsRV dysfunction is associated with increased oxygen consumption (also characterized by a higher risk for cardiac events) and impaired RV sympathetic function.

Artificial intelligence derived age algorithm after heart transplantation

Abstract Background An artificial intelligence (AI) algorithm detecting age from 12-lead ECG has been suggested to signal “physiological age” of the individual. Importantly, increased physiological age gauged by an increased difference between ECG-age and chronological age has been associated with higher risk of cardiac events in non-transplant population. Purpose We sought to investigate the validity of the AI-derived ECG-age algorithm in patients who underwent heart transplantation and its relationship to major adverse cardiovascular events (MACE). Methods A total of 489 consecutive patients who had undergone heart transplantation in our institution between 1994 and 2018 were studied. AI-ECG age was calculated by a previously-trained artificial intelligence (AI) algorithm using a 12-lead ECG per patient. ECGs used in the training process of the algorithm were excluded. The average of the ECG-ages within one year before and one year after heart transplantation was used to represent pre- and post-transplant ECG-ages. MACE was defined as any incidence of revascularization, re-transplantation, and death. Results Pre-transplant ECG-age (mean 63±10 years) correlated significantly with recipient chronological age (mean 50±13 years, r=0.57, p&amp;lt;0.0001), but this correlation between recipient and ECG-ages was weakened after transplantation (mean post-transplant ECG age of 55±10 years, r=0.34, p&amp;lt;0.0001). Interestingly, post-transplant ECG-age correlated significantly with donor age (mean ECG age of 55±10 years vs. mean donor age of 32±13 years, r=0.42, p&amp;lt;0.0001). During a median (IQR) follow-up of 9 (5, 14) years, 251 patients had MACE. Mean change in ECG age after transplantation compared to before was −8.8±12.7 years. Patients who had an increase in ECG-age after compared to before transplantation showed increased risk of MACE (HR: 1.53 [1.16, 2.01], p=0.002), independent of recipient and donor ages (adjusted HR: 1.68 [1.26, 2.25], p=0.001); whereas there were no significant differences in risk of MACE in patients who were transplanted with an older donor heart (HR: 1.07 [0.77, 1.50], p=0.66). In a Kaplan Meier survival analysis, those with increased ECG-age after transplantation had significantly lower MACE-free survival compared to those with decreased ECG-age. (Log-rank P=0.002; Wilcoxon P=0.001) (Figure) Conclusion Post-transplant ECG-age correlates more faithfully with the donor's than the recipient's chronological age, suggesting that ECG-age more closely reflects cardiac age than the patient age. Furthermore, ECG-age derived cardiac aging after transplantation is associated with higher risk of MACE. Funding Acknowledgement Type of funding sources: None.

Circulating Hydrogen Sulfide (H2S) and Nitric Oxide (NO) Levels Are Significantly Reduced in HIV Patients Concomitant with Increased Oxidative Stress Biomarkers.

Human immunodeficiency virus (HIV) attacks the immune system and weakens the ability to fight infections/disease. Furthermore, HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. The pathological mechanisms responsible for the increased incidence of cardiovascular disease in HIV patients are largely unknown. We hypothesized that increased oxidative stress and attenuated circulating levels of the cardioprotective gaseous signaling molecules, nitric oxide (NO), and hydrogen sulfide (H2S) were involved in the cardiovascular pathobiology observed in HIV patients. Plasma samples from both HIV patients and age–matched normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products (AOPP) and H2O2. Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H2S (free H2S and sulfane sulfur) and NO2 (nitrite) were determined in the plasma samples by using gas chromatography and HPLC, respectively. In the present study we observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. Circulating levels of the cardiovascular disease biomarkers: ADMA, hs-CRP (high-sensitivity C-reactive protein), and IL-6 were significantly increased in the circulatory system of HIV patients. The levels of both nitrite and H2S/sulfane sulfur were significantly reduced in the plasma of HIV patients as compared with normal subjects. Our data demonstrate significant increases in circulating biomarkers of oxidative stress and cardiovascular (CV) in conjunction with decreased bioavailability of H2S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV.

Culprit-Plaque Morphology and Residual SYNTAX Score Predict Cardiovascular Risk in Acute Myocardial Infarction: An Optical Coherence Tomography Study.

Aims: Culprit-plaque morphology [plaque rupture (PR) and plaque erosion (PE)] and high-risk plaques (HRP) identified by optical coherence tomography (OCT) and residual SYNTAX score (rSS) have been reported to influence clinical outcomes. Thus, in this study, we aimed to investigate the prognostic implication of culprit-plaque morphology and rSS for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Based on plaque morphology and rSS, 274 STEMI patients were divided into 4 groups: PE/low-rSS (n=61), PE/high-rSS (n=58), PR/low-rSS (n=55), and PR/high-rSS (n=100). According to HRP and rSS, patients were stratified to non-HRP/low-rSS (n=97), non-HRP/high-rSS (n=109), HRP/low-rSS (n=19), and HRP/high-rSS (n=49). MACE was defined as the composite of all-cause death, recurrence of myocardial infarction, stroke, and unplanned revascularization of any coronary artery. Results: During the follow-up of 2.2 years, 47 (17.2%) MACE were observed. Patients with PR/high-rSS and HRP/high-rSS presented lower survival probability on revascularization and MACE. In fully adjusted analyses, PR/high-rSS group presented higher MACE risk than PE/low-rSS (HR: 4.80, 95% CI: 1.43–16.11,P=0.025). Patients with non-HRP/high-rSS (HR: 2.90, 95% CI: 1.01–8.38,P=0.049) and HRP/high-rSS (HR: 8.67, 95% CI: 2.67–28.21,P＜0.001) presented higher risk of cardiac events than non-HRP/low-rSS. Adding rSS and HRP to the risk prediction model increased the C-statistic to 0.797 (95% CI: 0.737–0.857), with ΔC-statistic of 0.066 (P=0.002) and the NRI (46.0%, 95% CI: 20.5–56.8%,P＜0.001) and IDI (8.7%, 95% CI: 3.6–18.2%,P＜0.001). Conclusion: High-risk plaques in combination with rSS enhanced the predictive ability for MACE, indicating culprit-plaque features and residual atherosclerosis burden should be taken into account in risk stratification of STEMI patients.

Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study.

IntroductionDuring clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder.ObjectiveThe purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use.MethodsWe conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012–December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated.ResultsOverall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73–0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings.ConclusionsThis large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01095-7.

Physical health audit of gwent specialist substance misuse services (North Team)

Physical health audit of gwent specialist substance misuse services (North Team)

Thermoregulatory and cardiovascular responses in the elderly towards a broad range of gradual air temperature changes.

This study aimed to determine age-related differences in thermoregulatory and cardiovascular responses to a wide range of gradual ambient temperature (Ta) changes. Morphologically matched normotensive elderly and young males participated. The participants wearing only shorts rested during the 3-h experiment. After 30min of baseline at 28°C, Ta increased linearly to 43°C in 30min (warming) and then gradually decreased to 13°C in 60min (cooling). Ta was rewarmed to 28°C in 30min (rewarming), and that temperature was maintained for an additional 30min (second baseline). During the warming phase, there were no age-related differences in blood pressure (BP) and rectal temperature (Tre), despite a significantly lower cutaneous vascular conductance and heart rate in the elderly (P<0.05). At the end of the cooling phase, systolic blood pressure (SBP) in the elderly was significantly higher than the young (155.8±16.1 and 125.0±12.5mmHg, P<0.01). There was a consistent age group difference in SBP during rewarming. Mean skin temperature was significantly lower in the elderly during rewarming (P<0.05). Tre decreased more in the elderly and was significantly lower at the end of the experiment than the younger participants (36.78±0.34 and 37.01±0.15°C, P<0.05). However, there were no age group differences in thermal sensation. In conclusion, even normotensive elderly participants have a greater and more persistent BP response to cold than younger adults, suggesting that the elderly might be at a higher risk of cardiac events during cooling and subsequent rewarming.

Simple Two-Dimensional Echocardiographic Scoring System for the Estimation of Left Ventricular Filling Pressure

When left ventricular filling pressure (LVFP) increases, the mitral valve opens early and precedes tricuspid valve opening in early diastole. The authors hypothesized that a visually assessed time sequence of atrioventricular valve opening could become a new marker of elevated LVFP. The aim of this study was to test the diagnostic ability of a novel echocardiographic scoring system, the visually assessed time difference between mitral valve and tricuspid valve opening (VMT) score, in patients with heart failure. One hundred nineteen consecutive patients who underwent cardiac catheterization within 24hours of echocardiographic examination were retrospectively analyzed as a derivation cohort. In addition, a prospective study was conducted to validate the diagnostic ability of the VMT score in 50 patients. Elevated LVFP was defined as mean pulmonary artery wedge pressure (PAWP)≥15mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0=tricuspid valve first, 1=simultaneous, 2=mitral valve first). When the inferior vena cava was dilated, 1 point was added, and VMT score was ultimately graded as 0 to 3. Cardiac events were recorded for 1year after echocardiography. In the derivation cohort, PAWP was elevated with higher VMT scores (score 0, 10±5; score 1, 12±4; score 2, 22±8; score 3, 28±4mm Hg; P<.001, analysis of variance). VMT score ≥ 2 predicted elevated PAWP with accuracy of 86% and showed incremental predictive value over clinical variables and guideline-recommended diastolic function grading. These observations were confirmed in the prospective validation cohort. Importantly, VMT score ≥ 2 discriminated elevated PAWP with accuracy of 82% in 33 patients with monophasic left ventricular inflow in the derivation cohort. Kaplan-Meier analysis demonstrated that patients with VMT scores ≥ 2 were at higher risk for cardiac events than those with VMT scores ≤ 1 (P<.001). VMT scoring could be a novel additive marker of elevated LVFP and might also be associated with adverse outcomes in patients with heart failure.