Excess Cardiac Mortality Research Articles

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.

Abstract EP11: Long-term Outcomes Of Transcatheter Aortic Valve Replacement Compared With Surgical Aortic Valve Replacement: A Retrospective Cohort Study With Overlap Propensity Score Weighting

Objectives: This longitudinal observational study utilized surgical procedure data from Ontario, Canada to compare mid- and long-term clinical outcomes in a representative real-world cohort of patients (2007-2019) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Methods: A novel overlap weighting propensity score method was used to match patients on the date of TAVR or SAVR, conditional on baseline patient characteristics. Primary outcomes were all-cause and cardiovascular mortality either in-hospital or at 1, 3 and 5 years post-discharge. Secondary outcomes included ischemic stroke, hemorrhagic stroke, myocardial infarction, acute kidney injury, vascular complications, atrial fibrillation, endocarditis, permanent pacemaker implantation, defibrillator, reintervention, and cause-specific readmission at 1, 3 and 5 years post-discharge. In-hospital outcomes were compared using multivariable logistic regression. Long-term primary and secondary outcomes for patients undergoing TAVR vs. SAVR were compared using an overlap propensity score-weighted competing risks sub-distribution proportional hazards model. Results: The study included 9,355 SAVR and 2,641 TAVR patients. Hazards of all-cause mortality at 1 year (Hazard Ratio [HR], 1.25; 95% CI, 1.06-1.48), 3 years (HR, 1.48; 95% CI, 1.31-1.68) and 5 years (HR, 1.51; 95% CI, 1.36-1.69) were significantly higher in the TAVR compared to SAVR group. Cardiovascular mortality was significantly higher in the TAVR group at 3 (HR, 1.40; 95% CI, 1.08-1.80) and 5 years (HR, 1.41; 95% CI, 1.13-1.77). Non-cardiovascular mortality was also significantly higher in the TAVR group at 1 year (HR, 1.46; 95% CI, 1.03-2.06), 3 years (HR, 1.48; 95% CI, 1.17-1.88), and 5 years (HR, 1.41; 95% CI, 1.16-1.72). Hazards of myocardial infarction were significantly greater in the TAVR at 1 year (HR, 1.72; 95% CI, 1.08-2.74), 3 years (HR, 1.86; 95% CI, 1.35-2.57), and 5 years (HR, 1.82; 95% CI, 1.37-2.42). Hazards of angina readmission were significantly greater in the TAVR at 3 years (HR, 1.94; 95% CI, 1.26-3.00) and 5 years (HR, 1.87; 95% CI, 1.26-2.78). Conclusions: In real-life patients who underwent a TAVR experienced an excess cardiac and non-cardiac mortality compared to SAVR. More studies with long-term follow-up are needed to confirm the long-term clinical benefits of TAVR and effort to improve patient selection are warranted.

Rationale for Expanding the Use of Low-Dose Aspirin for Primary Cardiovascular Prevention during the COVID-19 Pandemic

The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over one million deaths especially in elderly persons with medical co-morbidities. While now waning, this epidemic continues to cause more than 500 fatalities per week mostly in individuals over70 years of age who are unvaccinated. Since viral epidemics have been shown to increase mortality due to atherosclerotic coronary heart disease and low-dose aspirin has been shown to reduce first myocardial infarctions by 44%, we recommend consideration of expanding the use of aspirin for primary cardiovascular prevention to reduce the cardiac morbidity and excess mortality associated with COVID-19 infections. Such aspirin use may be seen as especially appropriate for vulnerable elderly persons who qualify for treatment with Paxlovid (ritonavir-boosted nirmatrelvir) but are currently excluded for such in primary prevention guidelines of subspecialty societies. The rationale for this approach is further supported by recent proof of concept that vaccination, an alternative intervention for primary cardiovascular prevention, reduces the excess mortality associated with COVID-19 infection. Can greater use of aspirin for primary cardiovascular prevention mitigate the excess cardiac mortality associated with COVID-19 as shown with prior viral epidemics 1-3? Recommendations from the 2019 ACC/AHA and 2021 ESC guidelines currently advise limited aspirin use for primary prevention except in persons aged 40 to 59 years with elevated ASCVD risk scores (10-year risk ≥10%) and for those aged 60 to 69 years only with risk ≥20% in the context of no excess risk of bleeding (Figure 1) 4,5. These guidelines have been endorsed by the United States Preventive Services Task Force, which acknowledge that low-dose aspirin in the primary prevention setting reduces the risk of major atherosclerotic cardiovascular events including myocardial infarction and ischemic stroke offset by an increased risk of gastrointestinal bleeding 7,8. Currently endorsed guidelines specifically recommend against aspirin use in individuals at age 70 and beyond.

La mort subite cardiaque chez la femme, registre du nord de la Tunisie

BackgroundSudden cardiac death is a major public health problem. Epidemiological and clinical differences according to gender have been described in sudden cardiac death. The aim of this study was to examine the gender differences between autopsy findings and circumstance of occurrence associated with sudden cardiac death. MethodsWe prospectively collected epidemiological and autopsy data of victims of sudden cardiac death occurring in the northern governorates of Tunisia between January 2013 and December 2019. Symptoms preceding death, circadian, weekly and seasonal variations of sudden death were also analyzed. ResultsThe study population included 1834 men and 468 women with a mean age of 56.5±14.2 years. All cardiovascular risk factors except smoking were significantly more frequent among women but ischemic heart disease was the most common cause of death in men (51.3 %, versus 28 %, P<0.001). Women were more likely to have a negative macroscopic autopsy than men (34 % versus 23.6 %, P<0.001). Chest pain preceding sudden death was more frequent in male (24 % versus 13.2 %, P<0.001). In contrast, women were more likely to have dyspnea (8.1 % versus 15.6 %, P<0.001). Sudden death in women occurred indoors more often than in men (63.9 % versus 54.5 %, P<0.001) and also more often during night (midnight to 6 am). We also recorded an excess cardiac mortality in winter in both sexes. ConclusionsWomen had considerably more cardiovascular risk factors and more commonly negative macroscopic autopsy. Death occurred indoors and during night more often than in men.

Arrhythmias in COVID-19: clinical significance and management

Worldwide spread of coronavirus disease (COVID-19) caused overwhelming mortality rate during preceding half of the year 2020. Although coronavirus infection was known for mostly respiratory tract involvement, novel COVID-19 pandemic showed excessive cardiac mortality and arrhythmic complications. We aimed to summarize current literature and emphasize on underlying pathological mechanisms and global point of view to coronavirus and arrhythmia relationship. Key words: Coronavirus, COVID-19, arrhythmia

Cardiac Mortality in Kidney Transplant Patients: A Population-based Cohort Study 1988-2013 in Australia and New Zealand.

Transplant recipients experience excess cardiac mortality. We compared circulatory death rates in Australian and New Zealand kidney transplant recipients to the general population and identified risk factors for circulatory death in kidney transplant recipients. The primary cause of death for kidney transplant recipients aged ≥18 was established through ICD-10-AM codes using data linkage between the Australia and New Zealand dialysis and transplant registry and national death registers. We estimated standardized mortality ratios (SMRs) and developed a Fine-Gray competing risks model to determine risk factors for cardiac mortality. Of 5089 deaths in 16 329 kidney transplant recipients (158 325 person-years), 918 (18%) were cardiac. An increased risk of circulatory death was associated with older age (P < 0.001), male sex (P < 0.001), longer dialysis duration (P = 0.004), earlier era of transplantation (P < 0.001), ever graft failure (P < 0.001), known coronary artery disease (P = 0.002), and kidney failure from diabetes or hypertension (P < 0.001). The cardiac SMR was 5.4 [95% confidence interval (CI): 5.0-5.8], falling from 8.0 (95% CI: 4.9-13.1) in 1988 to 5.3 (95% CI: 4.0-7.0) in 2013 (P < 0.001). Females, particularly young ones, had significantly higher relative cardiac mortality than men. In recipients aged 40 years, the cardiac SMR was 26.5 (95% CI: 15.0-46.6) in females and 7.5 (95% CI: 5.0-11.1) for males. Cardiac risks remain elevated in kidney transplant recipients and may be under-recognized, and prevention and treatment interventions less accessed, less effective or even harmful in female recipients.

189P - Estimating radiotherapy-induced cardiovascular mortality in female breast cancer patients

BackgroundRadiotherapy halves the recurrence risk and reduces breast cancer death after breast sparing surgery, but it is associated cardiac morbidity and mortality (1). The EBCTCG data demonstrates an excess cardiac mortality rate ratio of 4,1% per increased Gray (Gy) whole heart dose (2). The aim of this study is to create a clinical applicable risk assessment model to predict 10-year cardiovascular mortality in female breast cancer patients. MethodsBy integration of the SCORE (Systematic COronary Risk Evaluation) risk charts and data of the EBCTCG we were able to develop cardiovascular mortality risk charts based on mean heart dose, age, systolic blood pressure, smoking-status and cholesterol for high- and low-risk regions in Europe, for contemporary mean heart doses of 2Gy, 4Gy and 8Gy. ResultsWe will present tables showing the 10-year cardiovascular mortality based on mean heart dose, smoking status, age, systolic blood pressure and cholesterol for high- and low-risk regions in Europe. Below you find the risk table for 60-years old non-smoking women in low-risk regions. A 60-year old, non-smoking patient from France (low-risk region) with a cholesterol 220mg/dl and a systolic blood pressure of 140mmHg has a 10-year cardiovascular mortality risk of 1,0%, adding radiotherapy with a mean heart dose of 4Gy will increase it to 1,1% and doubling the heart dose to 8Gy results in a risk of 1,2%. In contrast, a 65 year old smoking patient living in Bosnia (high-risk region) with a cholesterol of 260 and a systolic blood pressure of 160mmHg has a 10-year cardiovascular mortality risk of 13,0%, adding radiotherapy with a mean heart dose of 4Gy will increase it to 14,3% and doubling the heart dose to 8Gy results in a risk of 15,7%.Table189PTableCholesterol: 200-250mg/ml Mean Heart DoseCholesterol: 250-300mg/ml Mean Heart DoseSBP0Gy2Gy4Gy8Gy0Gy2Gy4Gy8Gy180mmHg3,03,23,33,64,04,24,44,9160mmHg2,02,12,22,42,02,12,22,4140mmHg1,01,11,11,22,02,12,22,4120mmHg1,01,11,11,21,01,11,11,2 ConclusionsIntegrating cardiovascular risk tables and radiotherapy data are useful for patient individualized radiotherapy and cardiovascular prevention after breast cancer treatment. (1) Lancet 2011;378(9804):1707-16. (2) J Clin Oncol 2017;35(15):1641-1649. Legal entity responsible for the studyThe authors. FundingVrije Universiteit Brussel. DisclosureAll authors have declared no conflicts of interest.

298. Dosimetric cardiac constraints for long-term cardiac mortality excess control during the tangential beams irradiation of the left breast

Purpose Careful evaluation of the heart-absorbed dose has to be adopted in any Radiotherapy Center and although a risk of cardiac death V 25 Gy 10 % is not sufficient to limit the excess cardiac mortality risk for each patient and for every RT schedule of tangential beams left sided breast RT. Aim of this work is to find a group of patient for which the dose constraint, above mentioned, is respected, but at a further investigation the excess cardiac mortality probability results greater than 1%. Than a correlation between these results and the dose volume histogram (DVH) has to be investigated and verified on a control group of patients. Methods and materials Analyzing the DVHs on TPS Philips Pinnacle3 of 240 women, who underwent to left sided breast tangential beams RT, came out that the constraint V 25 Gy 10 % was respected. By inspecting the integral DVHs some patients were individuated as “probable false negatives”. The Relative Seriality model ( α / β = 3 Gy , s = 1 , D 50 = 52.4 Gy and g = 1.28 ) was used as method to evaluate the probability of late cardiac mortality. Results For 19 patients the V 25 Gy was satisfied, but the probability of long-term cardiac mortality was found > 1% and up to 6%. The dosimetric heart constraints V 40 Gy and D 2 % showed a good correlation (R = 0.97 and R = 0.90 respectively) with the risk of cardiac death. To keep the probability lower than 1%, the cut off levels were determined by the simultaneous occurrence of the conditions: V 40 Gy 2 % , and D 2 % 38 Gy . The generalized gEUD was also valuated with an a = 5.7 For all calculations considering the EQD2Gy dose correction was considered. Conclusions This probability was only a calculation and not an observation of mortality. Anyway modern TPSs should promote, even more, the use of either radiobiological DVHs or algorithm optimization, especially in the era of hypofractionation.

Abstract P2-11-07: Evaluation of lung and heart dose in patients treated with radiation for breast cancer

Abstract BACKGROUND: A recent systematic review of women receiving radiation therapy (RT) for breast cancer combined with modeled estimated risks of mortality from heart disease and lung cancer found that the mean heart dose (MHD) was 4.4 Gy (5.2 Gy for left-sided, 3.7Gy for right-sided) and the mean total lung dose (TLD) was 5.7 Gy. Estimated excess cardiac mortality ranged from 0.3-1.2% and lung cancer mortality ranged from 0.2-4.4% with modern RT. Using these data as a benchmark, we set to review the MHD and mean TLD for our patients receiving adjuvant breast RT in a modern era when RT planning includes meeting normal tissue constraints. METHODS: We evaluated the MHD and mean TLD for patients with unilateral breast cancer treated with curative intent between January 2012 and May 2017 at our institution. Dosimetric data was complete for 793 patients. During this time period the MHD constraint was 4 Gy and lung V20 was 20% for breast only and 35% for regional nodal irradiation (RNI). RNI included the axillary, supraclavicular and internal mammary nodes.. Patients were evaluated by laterality (right vs. left), prone vs. supine position, breast only whole breast irradiation (WBI) and RNI with intact breast or chestwall post-mastectomy. The RNI group was examined by treatment technique, intensity modulated radiation therapy (IMRT) vs. 3D conformal (3DCRT). We compared differences in the MHD and mean TLD within those groups using the Student's t-test. RESULTS: We identified 651 patients: 481 WBI only and 170 RNI. In the RNI group, 77 (45.3%) received IMRT. Of the WBI only group, 229 (47.6%) were right-sided and 313 (65.1%) were treated prone. The mean TLD for the WBI only group was significantly lower in the prone vs. supine position (0.62 Gy vs. 3.90 Gy, p&amp;lt;0.0001). The prone position resulted in lower MHD for both left-sided WBI (1.17 Gy vs. 1.67 Gy, p&amp;lt;0.0001) and right-sided WBI (0.51 Gy vs. 0.64 Gy, p=0.1067). In patients that received RNI, the mean TLD was 8.20 Gy (SD 1.03) and the MHD was 2.67 Gy (3.25 Gy for left-sided vs. 1.83 Gy for right-sided, p=0.0001). Compared to 3DCRT, IMRT increased the MHD (2.46 Gy vs. 4.23 Gy for left-sided, p&amp;lt;0.0001; 0.94 Gy vs. 2.85 Gy, p&amp;lt;0.0001 for right-sided) and mean TLD (8.50 Gy vs. 7.95 Gy, p=0.0005). CONCLUSIONS: In the era of RT treatment planning that incorporates normal tissue constraints, very low MHD and lower TLD are achievable in prone or supine position patients receiving WBI only for breast conserving treatment. This means lower late cardiac and lung cancer mortality risks from RT. Women that receive RNI also have acceptably low MHD but high mean TLD. Node positive breast cancer patients derive a disease free survival benefit from RNI, which must be balanced against potential late risk for lung cancer, especially in smokers. More attention should be focused on identifying lung cancer risk, smoking cessation and screening efforts in node positive breast cancer patients with indications for RNI to minimize late radiation risks. Citation Format: Healy EH, Pratt DN, DiCostanzo D, Bazan JG, White J. Evaluation of lung and heart dose in patients treated with radiation for breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-07.

Long-Term Outcomes for Validation of Cardiac-Sparing Breast Cancer Treatment Techniques

The association between radiation therapy (RT) and ischemic vascular disease (IVD) has been known for many decades. The publication in 2013 of a retrospective study linking RT for left breast cancer to IVD has inspired numerous dosimetric studies aimed at reducing cardiac doses. The cardiac risk has been attributed to attempts to treat internal mammary lymph nodes (IMLN), most commonly using an anterior beam that delivered high doses to the origins of major vessels and much of the myocardium. If a treatment technique is producing clinically significant IVD we should see a detrimental effect on survival for patients with left breast cancers compared to those with right breast cancers. In 1983 our facility began using CT images to guide treatment planning. Initially, conformal molded blocks shaped tangent fields to protect the cardiac profile as much as possible. Anterior or oblique internal mammary fields became very rare. Since 2001 we have used 3D conformal CT planning and multi-leaf collimators to the same purpose. Deep inspiration breath hold is used when indicated. Between 1983 and 2011 a total of 3474 patients (1735 R, 1739 L) with first primary pathologic stages 0-III breast cancers were treated with this philosophy. Treatment generally covered the whole breast with standard doses (typically 45 – 50 Gy) and a boost. Since 1982 patient data has been abstracted by certified cancer registrars from general medical records and RT summary letters, and maintained on an in-house registry system. The registry has current follow-up on 95.6% of all cases in this group and was the source of data for this study. The two groups proved to be very closely matched in patient and tumor characteristics. Survival estimates were calculated for 30 years following diagnosis using the Kaplan-Meier method on 1 day intervals (table). These were compared using the log-rank test. Throughout the 30-year period of analysis the P-value was never smaller than 0.23 (briefly, at 7 years). Clinically significant IMLN recurrence has been very rare. Cause-specific mortality declined substantially after about 15 years but all-cause mortality remained elevated. For any RT technique, the average heart dose is substantially smaller for right breast cancers than it would be for left breast cancers. The equivalent survival seen with these two groups suggests that relatively simple alterations to treatment plans can virtually eliminate excess cardiac mortality from left breast irradiation without adverse consequences.Tabled 1Abstract 2130; Table 1LateralityTime from Dx (Yrs)051015202530RightAt Risk173514988944691935811Survival100.00%87.35%73.30%59.03%46.65%35.84%22.15%Std Err of Survival0.00%0.81%1.28%1.79%2.52%3.80%6.18%LeftAt Risk173914929124691816614Survival100.00%87.29%71.97%59.14%45.73%34.19%28.80%Std Err of Survival0.00%0.81%1.28%1.77%2.58%3.52%6.49% Open table in a new tab

Controversies in diagnosis and management of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a common condition; however, it appears to be overdiagnosed. Diagnosing CAP too frequently may be adding to the problems of overuse of antibiotics, such as bacterial resistance in the community and greater costs and complications in individuals. Data support that most patients with non-severe CAP can be treated for 3-5 days; however, most patients with CAP are receiving much longer courses of therapy. Macrolides such as azithromycin have the potential to prolong the QT interval, although large population studies show that this does not appear to result in excess cardiac mortality. CAP is associated with an increase in a variety of cardiac complications, most notably infarctions and worsening cardiac failure, so clinicians should be vigilant for signs and symptoms of these complications, particularly in patients with a history of ischaemic cardiac disease or the presence of cardiac risk factors. Cardiac risk factors should be assessed and managed in patients with CAP over 40 years of age, although there are yet to be data to show that this approach reduces deaths. Corticosteroids may have a slight effect on reducing deaths in patients with severe CAP, but this must be balanced against the significant potential for side effects.

Population-Based Long-Term Cardiac-Specific Mortality Among 34 489 Five-Year Survivors of Childhood Cancer in Great Britain.

Increased risks of cardiac morbidity and mortality among childhood cancer survivors have been described previously. However, little is known about the very long-term risks of cardiac mortality and whether the risk has decreased among those more recently diagnosed. We investigated the risk of long-term cardiac mortality among survivors within the recently extended British Childhood Cancer Survivor Study. The British Childhood Cancer Survivor Study is a population-based cohort of 34 489 five-year survivors of childhood cancer diagnosed from 1940 to 2006 and followed up until February 28, 2014, and is the largest cohort to date to assess late cardiac mortality. Standardized mortality ratios and absolute excess risks were used to quantify cardiac mortality excess risk. Multivariable Poisson regression models were used to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity and trends. Overall, 181 cardiac deaths were observed, which was 3.4 times that expected. Survivors were 2.5 times and 5.9 times more at risk of ischemic heart disease and cardiomyopathy/heart failure death, respectively, than expected. Among those >60 years of age, subsequent primary neoplasms, cardiac disease, and other circulatory conditions accounted for 31%, 22%, and 15% of all excess deaths, respectively, providing clear focus for preventive interventions. The risk of both overall cardiac and cardiomyopathy/heart failure mortality was greatest among those diagnosed from 1980 to 1989. Specifically, for cardiomyopathy/heart failure deaths, survivors diagnosed from 1980 to 1989 had 28.9 times the excess number of deaths observed for survivors diagnosed either before 1970 or from 1990 on. Excess cardiac mortality among 5-year survivors of childhood cancer remains increased beyond 50 years of age and has clear messages in terms of prevention strategies. However, the fact that the risk was greatest in those diagnosed from 1980 to 1989 suggests that initiatives to reduce cardiotoxicity among those treated more recently may be having a measurable impact.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

AbstractPurposeThis study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer.Methods and materialsUsing the CMS XiO Version 4·6 radiotherapy planning system's normal tissue complication probability (NTCP) algorithm and the Lyman–Kutcher–Burman model, we calculated the dose–volume histograms (DVH) indices for the ipsilateral lung and heart and the resultant NTCP for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients.ResultsIsocentric shifts in the posterior direction had the greatest effect on the lung V20, heart V25, and mean and maximum doses to the lung and the heart. DVH results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1 cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1 cm antero-posterior and left–right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0·73% to 3·4%, with a mean value of 1·7%. The maximum reported NTCP for radiation-induced pneumonitis was 5·8% (mean 2·6%) after 1 cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0% in 100% of the patients (n = 12) before and after set-up error simulations.ConclusionsSet-up errors in left-sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3 cm or less (CLD &lt; 3 cm), and a maximum heart distance of 1·5 cm or less (MHD &lt; 1·5 cm), the treatment plans could tolerate set-up errors of up to 1 cm without any change in the NTCP to the heart.

Mort subite d’origine cardiaque au nord de la Tunisie : variation circadienne, hebdomadaire et saisonnière

Several studies have reported a circadian variation in the occurrence of sudden cardiac death.To analyze the circadian, weekly and seasonal variations of sudden cardiac death occurring in northern Tunisia.We prospectively collected epidemiological and autopsic data of victims of sudden cardiac death occurring in the northern governorates of Tunisia between October 2010 and September 2012.The study population included 392 men and 108 women with a mean age of 52.3±15.8 years. Physical inactivity and smoking were the most common risk factors, they accounted for 76.4% and 57.9% respectively. Family history of sudden death was identified in 9.8% of victims. The vast majority of deaths occurred in a public place (41.4%) or at home (36.6%). Ischemic heart disease was the most frequent causes of death (269 cases). Sudden cardiac death was homogeneously distributed over the day. A maximum of events occurred on Sundays (17.8%) and a minimum on Mondays (11.4%), we also recorded an excess cardiac mortality in winter with a peak in December and a nadir in September (13% vs. 4.4% P=0.0001).In northern Tunisia, under Mediterranean climate, a winter excess cardiac mortality was found. Sudden cardiac death was homogeneously distributed over the day, however, an excess of mortality was recorded over the weekend with a nadir on Monday.

Analysis of 10-year cause-specific mortality of patients with breast cancer treated in New South Wales in 1995

The objective of this study is to assess cause-specific mortality for patients with breast cancer and to determine if excess cardiac death was associated with radiation therapy (RT). We obtained 10-year cause-specific mortality information from the New South Wales (NSW) Central Cancer Registry and National Death Index on 1242 patients with unilateral stage I-III invasive breast cancer in NSW, Australia, diagnosed over a 6-month period in 1995. We compared actuarial cause-specific mortality (breast cancer, cardiac, other cancers and other causes) for patients who received left-sided, right-sided or no RT. Mortality due to breast cancer or due to other cancers was not significantly different (P=0.30 and P=0.11) between the three subgroups. Mortality due to cardiac and other causes was higher in patients who did not have radiotherapy (P=0.001 and P<0.001). A total of 52 cardiac deaths in 1242 patients (4.2%) occurred - six of 274 patients (2.2%) in the left-sided radiotherapy group, four of 245 patients (1.6%) in the right-sided radiotherapy group (P=0.63) and 42 of 723 patients (5.8%) in the no radiotherapy group. Most cardiac deaths (46 of 52 cases) occurred in patients aged 70years or older at the time of diagnosis. There were no differences in cardiac mortality between the three treatment groups for those aged 70years or older (P=0.22, log-rank test), suggesting that the higher overall cardiac mortality rate in the no-RT group is due to a higher percentage of patients aged 70years or older. Of the 10 patients who died from cardiac causes and who had received RT, none had received chemotherapy or irradiation to the internal mammary chain. There is no excess cardiac mortality due to RT within the first decade in a population series of patients with breast cancer treated with modern radiotherapy.

Antiretroviral therapy 2010 update: Current practices and controversies

Over the past four years, significant advances have been made in human immunodeficiency virus (HIV) therapy. In addition to the release of two new classes of antiretrovirals, our understanding of the older antiretrovirals continues to improve. Multiple combination pills have been brought to market, simplifying the regimens for patient ease. New controversies have arisen, notably the role of antiretrovirals in the chronic inflammatory state that HIV infection produces, which may lead to excess cardiac, renal, and hepatic mortality. The optimum time to initiate antiretroviral therapy remains unknown but clinicians are treating HIV infection earlier in its course. In this article, we review these and other new issues relating to the care of the HIV patient.

Late potentials in the signal-averaged electrocardiogram in schizophrenia patients maintained on antipsychotic agents

In the present, preliminary, naturalistic study, cardiac ventricular late potentials (LPs), were measured in 33 physically healthy schizophrenia patients (13 - females and 26 - males, age - 45.5+/-8.8years) maintained on typical and atypical antipsychotic agents. These LPs represent delayed ventricular activation that might predispose to fatal ventricular arrhythmias and sudden cardiac death (SCD) in cardiac patients. Sixteen of the 33 patients ( approximately 48%) were found to be positive for LPs (compared to 3.7-6% in the general population). No association was found with any of the following: drug type, anti-cholinergic burden, daily dose of antipsychotic agents, age, gender, disease duration, QT(c) interval and QT dispersion. Further large-scale longitudinal prospective studies are warranted to substantiate our findings and to clarify their impact on the excess cardiac morbidity and mortality in schizophrenia patients.

Feasibility of Postmastectomy Treatment With Helical TomoTherapy

To investigate the potential of helical tomotherapy for postmastectomy radiation therapy. By use of the TomoTherapy Hi-Art II treatment-planning system (TomoTherapy Inc., Madison, WI), helical tomotherapy dose plans were developed for 5 patients and compared with the mixed-beam (electron-photon) plans with which they had been treated. The TomoTherapy plans were evaluated by use of dose-volume quantities, tumor control probability, normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The TomoTherapy plans showed better dose homogeneity in the planning treatment volume containing the chest wall and internal mammary nodes (p = 0.001) and eliminated the need for abutting fields. For the normal tissues, the TomoTherapy plans showed a smaller fractional volume receiving 20 Gy or greater for the ipsilateral lung (p = 0.05), no change in NTCP for postradiation pneumonitis, increased SCCP for each lung and both lungs together (p < 0.02), no change in the volume of the heart receiving more than 15 Gy, no change in NTCP for excess cardiac mortality, and a larger mean dose and SCCP in the contralateral breast (p < 0.001). For nonspecific tissues, the volume receiving between 5 Gy and 25 Gy and SCCP were both larger for the TomoTherapy plans (p < 0.01). Total SCCP was larger for the TomoTherapy plans (p = 0.001). Overall, the TomoTherapy plans had comparable tumor control probability and NTCP to the mixed-beam plans and increased SCCP. The TomoTherapy plans showed significantly greater dose homogeneity in the chest wall, which offers the potential for improved cosmesis after treatment. These factors have resulted in TomoTherapy often being the treatment of choice for postmastectomy radiation therapy in our clinic.

Cardiac disease and second lung cancer after radiotherapy for breast cancer

Radiotherapy (RT) is an important tool in the multidisciplinary management of breast cancer. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis of randomised clinical trials demonstrated that the addition of RT to breast cancer therapy resulted in a significant reduction in the risk of local breast cancer recurrence, leading to a reduction in the risk of mortality. For every four local recurrences avoided by RT in years 1–5, about one death from breast cancer was avoided by year 15 [1]. However, when targeting the breast/chest wall with RT, some radiation is also delivered to the underlying normal tissues (e.g. heart and lung), and RT has been associated with an increased risk of late onset cardiotoxicity and second malignancies. In the EBCTCG analysis there was a significant excess of fatal heart disease (rate ratio 1.27, standard error (SE) 0.07, P = 0.0001) among irradiated women. Similarly, an excess incidence of second lung cancer (rate ratio 1.61, SE 0.18, P = 0.0007) and lung cancer deaths (rate ratio 1.78, SE 0.22, P = 0.0004) was found for irradiated patients. These long term side effects tend to offset the beneficial effect of RT. For example, in the meta-analysis, overall survival remained significantly improved for women given breast conserving surgery and for women with node-positive disease treated with mastectomy and axillary clearance, but for women with node-negative disease treated with mastectomy and axillary clearance, the beneficial effect of RT on breast cancer survival was very small and the toxic side effects outweighed it. The amount of incidental radiation delivered to the underlying heart is greater with left-sided versus right-sided RT. Similarly, the amount of incidental lung irradiation will generally be greater for the ipsilateral versus contralateral lung. These differences in exposure have been used to evaluate the risk of cardiac disease and second lung cancer associated with RT. Among women diagnosed with breast cancer during 1973–1982 in US SEER cancer registries, an excess cardiac mortality (ratio of 1.42 (1.11−1.82)) for left-side irradiated patients, and excess lung cancer mortality (ratio of 2.00 (1.00–4.00)) for ipsilateral lung cancer at 10–14 years after RT was found [2]. These excess risks increased significantly and progressively with time since RT: cardiac mortality 1.58 (1.29–1.95) and ipsilateral lung cancer mortality 2.71 (1.65–4.48) at 15 years or more after RT. The risk of late radiation-associated sequelae with modern cancer treatment is uncertain, because older radiotherapy regimens resulted in larger cardiac dosevolume distributions to organs at risk than what is common with modern radiation techniques [3,4]. Nearly all of the above mentioned studies analysed data from an era before the routine use of threedimensional (3-D) simulation and planning, which allows for more accurate delineation of irradiated heart and lung volumes. Coincident with improvements in RT techniques, there have been observations of decreased incidence of radiation-associated sequelae over time [2,5]. Current research in this area is attempting to define more precisely the risk of radiation-associated sequelae and to deliver RT with improved sparing of organs at risk. A case-control study in Sweden and Denmark, Radiation-Associated Cardiovascular Events (RACE), is estimating irradiated cardiac volumes and correlating estimated cardiac dose with clinical events in an attempt to characterise the cardiac dose-response relationship [6]. Similarly, estimates of the mean ipsilateral lung RT dose have allowed for assessment of second lung cancer risk by RT dose. Two separate studies have reported an estimated increase in the relative risk for second lung cancer of approximately 0.1−0.2 per Gy (mean ipsilateral lung radiation dose) at 10 or more years after RT [7,8]. Other cancer treatment factors may also potentially increase the risk of late sequelae. Chemotherapeutic agents have changed over time, and newer agents such as anthracycline chemotherapy (doxorubicin and epirubicin) and immunotherapy (trastuzumab), which are themselves cardiotoxic, are increasingly being

Analysis of cardiac and pulmonary complication probabilities after radiation therapy for patients with early-stage breast cancer

The purpose of this study was to evaluate the radiobiological implications of clinical use of respiratory-gated techniques for postoperative radiation therapy of early-stage left-sided breast cancer after breast-conserving surgery. Radiation therapy treatment plans of 80 patients with early-stage breast cancer (stage I-II), receiving whole breast irradiation after breast-conserving therapy, were analyzed. The control group consisting of 47 patients received standard radiation therapy, and the respiratory-gated group consisting of 33 patients received deep inspiration-gated radiation therapy. Normal tissue complication probabilities (NTCP) for cardiac mortality and for clinical radiation-induced pneumonitis were calculated for all patients included in present study, using relative seriality model. NTCP data were analyzed for 113 radiation therapy plans, which included free breathing plans for the respiratory-gated groups. Pneumonitis probability was 0.6% (range 0.0-2.8%) and 0.3% (0.0-1.2%) for control and respiratory-gated group, respectively. Cardiac mortality was 1.3% (0.0-5.0%) and 0.2% (0.0-2.8%) for control and respiratory-gated group, respectively. Using respiratory-gated radiation therapy, NTCP was reduced in comparison with the control group by 83% (P<0.00001) and by 55% (P=0.01270) for cardiac mortality and for clinical radiation-induced pneumonitis, respectively. Use of respiratory-gated radiation therapy, for postoperative treatment of early-stage breast cancer, significantly reduces excessive cardiac mortality probability and pulmonary complication probability, as compared to standard radiation therapy techniques. This is especially important from heart complication probability point of view, as cardiac mortality remains one of the important issues of postoperative breast irradiation in patients with early stage breast cancer.