Late Cardiac Mortality Research Articles

Prognostic Implication of Preprocedural Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis.

Pulmonary hypertension (PH) is a common comorbidity in patients with aortic stenosis (AS) who are candidates for transcatheter aortic valve implantation (TAVI). Herein, we sought to elucidate the prognostic value of preprocedural PH on the early and late mortality after TAVI. The Cochrane Library, Scopus, PubMed, Web of Science, Embase, and ProQuest were screened using a predefined search query. We considered odds ratios (ORs) as the measure of effect. Meta-regression analysis was applied to investigate the potential impact of baseline characteristics on the outcomes. Egger's and Begg's tests were used to assess the publication bias. Thirty-three studies comprising 34 datasets representing 68,435 patients were included in the analysis. Regardless of the definition and severity of PH, pooled data analysis indicated that preprocedural PH was associated with higher cardiac and overall 30-day [OR, 1.45 (1.15-1.82) and OR, 1.75 (1.42-2.17), respectively], and 1-year mortality [OR, 1.63 (1.35-1.96) and OR, 1.59 (1.38-1.82), respectively]. Meta-regression analysis demonstrated that older age, higher New York Heart Association function class, history of hypertension, diabetes, and lower left ventricular ejection fraction were predictors of higher mortality rate following TAVI. Moreover, we found that preprocedural PH is significantly associated with higher in-hospital mortality and 30-day acute kidney injury. Our results demonstrated that preprocedural PH is associated with higher early and late cardiac and overall mortality following TAVI; however, this finding is limited regarding the considerable inconsistency in the definition of PH and PH severity among studies.

Impact of Dose Calculation Algorithms and Radiobiological Parameters on Prediction of Cardiopulmonary Complications in Left Breast Radiation Therapy.

Breast cancer requires evaluating treatment plans using dosimetric and biological parameters. Considering radiation dose distribution and tissue response, healthcare professionals can optimize treatment plans for better outcomes. This study aimed to evaluate the effects of the different Dose Calculation Algorithms (DCAs) and Biologically Model-Related Parameters (BMRPs) on the prediction of cardiopulmonary complications due to left breast radiotherapy. In this practical study, the treatment plans of 21 female patients were simulated in the Monaco Treatment Planning System (TPS) with a prescribed dose of 50 Gy in 25 fractions. Dose distribution was extracted using the three DCAs [Pencil Beam (PB), Collapsed Cone (CC), and Monte Carlo (MC)]. Cardiopulmonary complications were predicted by Normal Tissue Complication Probability (NTCP) calculations using different dosimetric and biological parameters. The Lyman-Kutcher-Burman (LKB) and Relative-Seriality (RS) models were used to calculate NTCP. The endpoint for NTCP calculation was pneumonitis, pericarditis, and late cardiac mortality. The ANOVA test was used for statistical analysis. In calculating Tumor Control Probability (TCP), a statistically significant difference was observed between the results of DCAs in the Poisson model. The PB algorithm estimated NTCP as less than others for all Pneumonia BMRPs. The impact of DCAs and BMRPs differs in the estimation of TCP and NTCP. DCAs have a stronger influence on TCP calculation, providing more effective results. On the other hand, BMRPs are more effective in estimating NTCP. Consequently, parameters for radiobiological indices should be cautiously used s to ensure the appropriate consideration of both DCAs and BMRPs.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data

BackgroundDespite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. ObjectivesThe aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. MethodsIn a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. ResultsIn total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. ConclusionsIn this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

Outcomes of Preprocedural Pulmonary Hypertension on All-Cause and Cardiac Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review.

Patients with symptomatic aortic stenosis (AS) commonly have an associated finding of pulmonary hypertension (PH), and it has been previously shown to have increased morbidity and mortality following surgical aortic valve repair (SAVR) as well as transcatheter aortic valve implantation (TAVI). There are no guidelines stating the cut-off point for PH at which the patient can safely undergo TAVI with benefits outweighing the risks. This is partly due to the lack of uniformity in the PH definition used in various studies. This systematic review sought to study the effect of preprocedural pulmonary hypertension on early and late all-cause and cardiac mortality in patients undergoing TAVI.We performed a systematic review of studies comparing patients with AS undergoing TAVI having PH. The review was undertaken as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified from PubMed, Pubmed Central (PMC), Cochrane, and Medline on January 10, 2022, for literature published until January 10, 2022. MeSH strategy was used on PubMed to search the literature, and filters were applied to search only Observational Studies, randomized controlled trials(RCT), and meta-analysis.A total of 170 unique articles were identified and screened. Of the 33 full-text articles that were reviewed, 18 articles, including duplicates, were excluded. Fifteen articles fulfilled the selection criteria and were included in this review. The study design included two meta-analyses, one randomized control trial, one prospective cohort study, and 11 retrospective cohortstudies.The studies involved a total of approximately 30,000 patients. The observational studies in our review were of good to fair quality, the RCT had a low to moderate bias, and the meta-analysis was of moderate quality. Baseline PH and persistence of PH post-TAVI are strongly associated with all-cause and cardiac mortality. Few studies have shown that a decrease in post-TAVI PH carries mortality benefits. Therefore, efforts should be made to identify mechanisms of persistent PH post-TAVI and whether interventions to reduce PH pre-TAVI will have any clinical implications or not by conducting RCT.

Impact of Chronic Kidney Disease on Outcomes of Percutaneous Coronary Intervention in Patients With Diabetes Mellitus: A Systematic Review and Meta-Analysis.

The impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes after percutaneous coronary intervention in patients with diabetes mellitus (DM) is still unclear. This study aimed to systematically assess evidence on this topic. The PubMed, Embase, and CENTRAL databases were searched for studies comparing mortality, myocardial infarction (MI), or revascularization outcomes between patients with DM with and without CKD. In 11 studies, the presence of CKD was associated with significantly increased risk of early all-cause mortality (risk ratio [RR], 3.45; 95% CI, 3.07-3.87; I2 = 0%; P < .001), late all-cause mortality (RR, 2.78; 95% CI, 1.92-4.02; I2 = 83%; P < .001), cardiac mortality (RR, 2.90; 95% CI, 1.99-4.22; I2 = 29%; P < .001), and MI (RR, 1.40; 95% CI, 1.06-1.85; I2 = 13%; P = .02) compared with no CKD. There was no difference in the risk of any revascularization between those with and without CKD. Analysis of adjusted hazard ratios (HRs) indicated significantly increased risk of mortality (HR, 2.64; 95% CI, 1.91-3.64; I2 = 0%; P < .001) in the CKD group but only a nonsignificant tendency of increased MI (HR, 1.59; 95% CI, 0.99-2.54; I2 = 0%; P = .05) and revascularization (HR, 1.24; 95% CI, 0.94-1.63; I2 = 2%; P = .12) in the CKD group. The presence of CKD in patients with DM significantly increases the risk of mortality and MI. However, CKD had no impact on revascularization rates.

Long-Term Clinical Outcomes of the On-X Mechanical Prosthetic Valve in the Aortic or Mitral Position - A Single-Center Experience of up to 20 Years' Follow up.

This study evaluated the long-term outcomes for up to 20 years after On-X mechanical valve implantation in the left side of the heart.Methods and Results:Between 1999 and 2015, 861 patients (mean age=51.6±10.9 years) who underwent prosthetic valve replacement using the On-X valve in the aortic or mitral position were enrolled (aortic=344, mitral=325, double=192). The mean clinical follow-up duration was 10.5±5.3 (median 10.9) years. Operative mortality occurred in 26 patients (3.0%), and linearized late cardiac mortality was 0.9%/patient-year without an intergroup difference. Linearized thromboembolism, bleeding, prosthetic valve endocarditis, non-structural valve deterioration (NSVD), and reoperation rates were 0.8%/patient-year, 0.6%/patient-year, 0.2%/patient-year, 0.5%/patient-year, and 0.5%/patient-year, respectively. Prosthetic valve endocarditis was more frequent after double valve replacement than after aortic or mitral valve replacement (P=0.008 and 0.005, respectively). NSVD and reoperation rates were significantly lower aortic valve replacement than after mitral or double valve replacement (P=0.001 and 0.002, P=0.001 and <0.001, respectively). Valve replacement in the mitral position was the only risk factor for NSVD (hazard ratio [95% confidence interval]=5.247 [1.608-17.116], P=0.006). On-X valve implantation in the left side heart had favorable clinical outcomes with acceptable early and late mortality and a low incidence of prosthetic valve-related complications. Particularly in the aortic position, the On-X valve had better long-term non-structural durability.

Early vs. Late Onset Cardiac Injury and Mortality in Hospitalized COVID-19 Patients in Wuhan.

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown.Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI.Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56–73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P < 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472–35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125–22.388) compared to patients with early CI but no recurrence.Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.

Outcomes after surgical ventricular restoration for ischemic cardiomyopathy

ObjectiveThe study objective was to evaluate the short- and long-term outcomes of patients with ischemic cardiomyopathy after surgical ventricular restoration and to identify risk factors related to poor results. MethodsBetween August 2002 and April 2016, 62 patients affected by ischemic cardiomyopathy underwent surgical left ventricular restoration at our unit. Patients' mean age at operation was 63 years (39-79 years). Mean ejection fraction was 29.6%. The Surgical Treatment for Ischemic Heart Failure trial criteria have been used as indications for surgery. Fifty-seven patients (91%) received surgical myocardial revascularization. Mitral valve repair was performed in 39 patients (63%). The surgical technique consisted of the classic Dor operation or a different approach reducing the equatorial diameter of the left ventricle and avoiding the use of a patch. The data were analyzed retrospectively for perioperative results and short- and long-term clinical outcomes. ResultsOne patient died of noncardiac causes within 30 days (1.6%). All-cause death occurred in 36 patients (58%) during follow-up (0.6-14.7 years; median follow-up time, 7.02 years), of whom 15 died of cardiac causes. Age, need for preoperative intra-aortic balloon pump, reduction less than 35% of postoperative left ventricular end-diastolic and end-systolic volumes, type of surgical technique, and ejection fraction less than 25% were identified as risk factors for late cardiac mortality. Perioperative levosimendan administration and presence of preoperative moderate to severe mitral regurgitation influenced early and intermediate-term outcomes, but no statistical relevance on long-term results was demonstrated. ConclusionsPatients with ischemic dilative cardiomyopathy have favorable short- and long-term outcomes after ventricular restoration. Age, preoperative ejection fraction less than 25%, inadequate left ventricular surgical reverse remodeling, and type of surgical technique negatively affect long-term survival.

Outcome after surgical repair of tetralogy of Fallot: A systematic review and meta-analysis

IntroductionTetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Intracardiac correction was pioneered by Walton Lillehei in 1955 and has since then gone through major developments. The aim of this study was to provide a systematic literature review of published results on the long-term outcome of complete surgical correction of TOF. MethodsMEDLINE, PubMed, Embase, Web of Science, Cochrane, and Google Scholar were systematically searched for literature published between January 2000 and July 2018. Pooled estimates with a random effects model after log-transformation were calculated for mortality and reintervention. Potential heterogeneity was assessed by subgroup analyses and meta-regression. ResultsA total of 143 papers of 137 distinct cohorts comprising 21,427 patients and total follow-up duration of 147,430 patient-years were included. Overall mean age at correction was 3.7 ± 5.6 years, but excluding papers exclusively focusing on correction in adults yielded a mean age of 0.5 ± 2.5 years at correction. Previous palliative shunts (107 studies), a transventricular approach (81 studies), and a transannular patch (124 studies) were used in 16% (range 0%-78%), 39% (range 0%-100%), and 49% (range 0%-100%) of the patients. respectively. In case a transannular patch was used, monocusp reconstruction was applied in 15% (range 0%-100%) (49 studies). The most common genetic abnormality was Down syndrome, with a pooled estimated prevalence of 4.6% (range 0%-12.3%). The pooled estimates of early and late mortality were 2.84% (95% confidence interval [CI], 2.34-3.45) and 0.42%/year (95% CI, 0.33-0.54), respectively. The pooled estimate of late cardiac mortality was 0.26%/year (95% CI, 0.21-0.34). Valve-related mortality and non–valve-related mortality had pooled estimates of 0.20%/year (95% CI, 0.15-0.26) and 0.17%/year (95% CI, 0.12-0.22), respectively. The pooled estimate of reintervention was 2.26%/year (95% CI, 1.86-2.75). ConclusionsTOF can be surgically corrected at a young age with low perioperative and long-term mortality. Life-long intensive follow-up and substantial reintervention rates characterize the clinical course.

Left Ventricular Speckle Tracking Echocardiography Changes Among Early-stage Breast Cancer Patients Three Years After Radiotherapy

Chest radiotherapy (RT) doubles late cardiac mortality. This study aimed to evaluate the evolution of cardiac changes in speckle tracking echocardiography during a three-year follow-up. This prospective study included 81 chemotherapy-naïve early-stage breast cancer patients who were evaluated at baseline, immediately after RT and three years after RT. Sixty-one patients had left-sided (LSBC) and 20 right-sided breast cancer (RSBC). Global longitudinal strain (GLS) declined from baseline -18.0±3.3% to -17.0±3.0% (p=0.015) at the three-year follow-up examination. A decline over 15% (GLS15) was observed in 19 (27%) patients. GLS15 was independently associated with aromatase inhibitor use (β=-1.977, p=0.001). In regional analysis, patients with LSBC had apical strain decline by 3.2±5.5% (p<0.001) and patients with RSBC showed basal rotation decline by 1.8° (-0.2°, 3.8°) (p=0.030). Even contemporary RT induced progressive global and regional decline in speckle tracking analysis. The regional changes complied with RT fields.

Prognosis of CT-derived Fractional Flow Reserve in the Prediction of Clinical Outcomes.

To examine the prognostic implication of fractional flow reserve (FFR) derived from coronary CT (FFRCT) in routine clinical practice. Patients referred for FFRCT analysis at a single center between October 2015 and June 2017 were retrospectively included and followed up for rates of invasive angiography and clinical events. Two hundred seven patients underwent successful FFRCT analysis with seven lost to follow-up, leaving 200 (mean age ± standard deviation, 62.4 years ± 10.0; 49 [24.5%] women) patients for analysis. At coronary CT angiography, patients were categorized as having significant stenosis (SS) in the presence of a diameter stenosis greater than or equal to 50% (hereafter, SS positive) and flow limitation in the presence of a postlesion (that is, FFRCT measured 2 cm to the distal aspect of the lesion) FFRCT less than 0.80 (hereafter, FFRCT positive). Vessel-oriented clinical events (VOCEs) were defined as vessel-related late revascularization (>90 days), myocardial infarction, and cardiac mortality. At CT angiography, 130 (65%) studies were SS positive and 63 (31.5%) were FFRCT positive. At median follow-up of 477 days (range, 252-859 days), there were 26 VOCE end points in 22 patients: 22 revascularizations and four nonfatal myocardial infarctions. VOCE end points occurred in zero of 58 (0%) of SS-negative and FFRCT negative patients, in eight of 79 (10.1%) of SS-positive and FFRCT-negative patients, in zero of 12 (0%) of SS-negative and FFRCT-positive patients, and in 18 of 51 (35.3%) of SS-positive and FFRCT-positive patients (log-rank χ2 = 30.1; P < .001). At multivariable Cox regression, both FFRCT (hazard ratio per 0.1 decrease, 1.54 [95% confidence interval: 1.1, 2.2] P = .013) and stenosis (hazard ratio per unit increase, 2.16 [95% confidence interval: 1.25, 3.72] P = .006) were independently associated with VOCE. Stenosis and FFRCT are independent predictors of intermediate-term outcomes. In the absence of a stenosis greater than 50%, a positive FFRCT result is not associated with an increased intermediate risk.© RSNA, 2019Supplemental material is available for this article.See also commentary by Fairbairn and Bull in this issue.

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.

TAVR in Patients with a Low STS Score: A Cohort Study with a Mean Follow Up of 2 Years.

Partner 2 and SURTAVI trials (mean STS score of 5.8 and 4.5) support extending TAVR into the intermediate risk group. We present our results of TAVR in a group with mean STS score of 2.9 and 2 year follow up. This is a prospective cohort study of 46 consecutive patients undergoing TAVR between 2011 and 2016. All patients had severe symptomatic AS. Age, functional status, coronary disease, co-morbidity and imaging parameters were assessed. Patients were followed up for 12-60 months. 46 patients with a mean age of 75 years were enrolled. Mean EF 56%, mean MG 52 mm Hg and mean PG 87 mm Hg. The mean STS score was 2.9. Forty-two underwent transfemoral and 4 transaortic TAVR. Forty-five of 46 valves were implanted successfully. One patient had moderate perivalvular regurgitation (PVR). Post-procedure mean MG was 11 mm Hg. There was one procedure related stroke and one intraprocedural death. Five patients (10.8%) required a permanent pacemaker. 30-day mortality was 2 of 46 (4.3%). Mean follow up was 28 months. Mean MG at 2 years was 12 mm Hg. Late cardiac mortality occurred in 1 patient. TAVR in this group with a low STS score was successful with excellent valve performance. Although the STS score identifies intermediate and high risk patients, it does not account for the overall frailty and limited mobility of many elderly patients placing them at a higher surgical risk despite their low STS scores. A scoring system that captures all such factors is required. Finally, a large scale randomized trial with long term follow up determining the validity of TAVR in truly low risk individuals is necessary.

Cell therapy and left ventricular restoration for ischemic cardiomyopathy: long-term results of a perspective, randomized study.

Aim of this study is to verify the potential advantages and benefits of bone-marrow derived autologous stem cells implantation associated to surgical left ventricular restoration (SVR), to report a new modality of cell delivery to myocardium, and to identify possible side effects of this procedure. Between March 2007 and March 2013, 30 patients affected by ischemic dilative cardiomyopathy who received a SVR operation were enrolled in the study. The population was divided in two groups:16 patients were randomly assigned to receive stem cells therapy in addition to SVR (groupA), 14 patients received a placebo (group B). The two groups were homogeneous in respect of age, gender, preoperative NYHA class, mitral incompetence and left ventricular sizes and volumes. The patients were evaluated by echo and pet-scan before surgery and at 6 months follow-up, and by echo at subsequent follow-up. Overall 30 days-in hospital mortality was 0 for the entire cohort. At last follow-up ejection fraction increased from 25.3% before surgery to 36.3% in group A, and from 31.8% to 45.6% in group B. Reduction of LVEDD was 6% in group A, 9% in group B. ESLVV and EDLVD decreased more significantly in patients receiving stem cells (55% vs. 35%). Late cardiac mortality at 9 years follow-up was similar in the two groups of patients. No early or late adverse reaction nor cases of infections were observed. Patients affected by ischemic cardiomyopathy have a favourable outcome after SVR. A higher reduction of LVEDV and LVESV assessed by CT-Scan evaluation in patients receiving cell therapy, when compared to control group, encourages the evolution and refinement of myocardial regenerative therapy added to SVR.

The predictive value of baseline pulmonary hypertension in early and long term cardiac and all-cause mortality after transcatheter aortic valve implantation for patients with severe aortic valve stenosis: A systematic review and meta-analysis.

Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH). To determine the association of PH with early and late cardiac and all-cause mortality after TAVI. We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed. In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality). This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.

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.

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.

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range = 2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac tests.

Adjuvant High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for High-Risk Primary Breast Cancer: Results from the Italian National Registry

The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)–positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials.

Fate of functional tricuspid regurgitation in aortic stenosis after aortic valve replacement

Functional tricuspid regurgitation (TR) is found not infrequently in conjunction with aortic stenosis. The aim of the present study was to evaluate the changes in TR and to identify the predictors of late progression after aortic valve replacement. We evaluated 354 patients who had undergone aortic valve replacement for aortic stenosis from January 1995 to December 2009. Patients with mitral regurgitation were excluded. Of the 354 patients, 54 had TR greater than mild. The mean follow-up duration was 4.4±4.3 years (maximum, 15). The serial echocardiographic and clinical data were analyzed. No early mortality occurred, and the late cardiac mortality rate was 3.9% (14 of 354). In the 48 patients with TR greater than mild, TR did not improve in 23 (49.1%) during the follow-up period. Freedom from cardiac mortality at 10 years was lower in those with TR greater than mild than in patients without TR (61.6%±16.7% vs 93.0%±2.9%, P=.008). Left ventricular diastolic function correlated with right ventricular systolic pressure (P<.001) and the degree of TR during follow-up (P=.001). Multivariate analysis showed that postoperative atrial fibrillation (odds ratio, 6.8; P=.001) and the aortic transprosthetic mean pressure gradient (odds ratio, 1.1; P=.028) predicted late TR greater than mild. Not only did TR in patients with aortic stenosis frequently persist after aortic valve replacement, it was progressive in some. This finding was associated with left ventricular diastolic dysfunction. A concomitant tricuspid valve procedure could be considered in selected patients with aortic stenosis to avoid late TR.