Sex Differences in Pulmonary Hypertension and Associated Right Ventricular Dysfunction.

Background: Prior studies have established the impact of sex differences on pulmonary arterial hypertension (PAH). However, it remains unclear whether these sex differences extend to other hemodynamic subtypes of pulmonary hypertension (PH). Methods: We examined sex differences in PH and hemodynamic PH subtypes in a hospital-based cohort of individuals who underwent right heart catheterization between 2005-2016. We utilized multivariable linear regression to assess the association of sex with hemodynamic indices of RV function [PA pulsatility index (PAPi), RV stroke work index (RVSWI), and right atrial: pulmonary capillary wedge pressure ratio (RA:PCWP)]. We then used Cox regression models to examine the association between sex and clinical outcomes among those with PH. Results: Among 5208 individuals with PH (mean age 64 years, 39% women), there was no significant sex difference in prevalence of PH overall. However, when stratified by PH subtype, 31% of women vs 22% of men had pre-capillary (P<0.001), 39% vs 51% had post-capillary (P=0.03), and 30% vs 27% had mixed PH (P=0.08). Female sex was associated with better RV function by hemodynamic indices, including higher PAPi and RVSWI, and lower RA:PCWP ratio (P<0.001 for all). Over 7.3 years of follow-up, female sex was associated with a lower risk of heart failure hospitalization (HR 0.83, CI 95% CI 0.74- 0.91, p value <0.001). Conclusions: Across a broad hospital-based sample, more women had pre-capillary and more men had post-capillary PH. Compared with men, women with PH had better hemodynamic indices of RV function and a lower risk of HF hospitalization. CLINICAL PERSPECTIVE: What Is New? Although sex differences have been explored in pulmonary arterial hypertension, sex differences across pulmonary hypertension (PH) in broader samples inclusive of all hemodynamic subtypes remain less well definedWe delineate sex differences in hemodynamic subtypes of PH and associated right ventricular function in a large, heterogenous, hospital-based sample of individuals who underwent right heart catheterizationSex has a significant impact on prevalence of PH across hemodynamic subtypes as well as associated RV function What Are the Clinical Implications? Understanding sex differences across different PH hemodynamic subtypes is paramount to refining risk stratification between men and womenFurther elucidating sex differences in associated RV function and clinical outcomes may aid in developing sex-specific therapies or management strategies to improve clinical outcomes.

Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction.

BACKGROUND: Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear. METHODS: We examined patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction (pulmonary artery pulsatility index, right atrial pressure:pulmonary capillary wedge pressure ratio, RV stroke work index). Cox models were used to examine the association of RV function measures with clinical outcomes. RESULTS: Among 8285 patients (mean age, 63 years; 40% women), higher body mass index was associated with worse indices of RV dysfunction, including lower pulmonary artery pulsatility index (ß, -0.23; SE, 0.01; P<0.001), higher right atrium:pulmonary capillary wedge pressure ratio (ß, 0.25; SE, 0.01; P<0.001), and lower RV stroke work index (ß, -0.05; SE, 0.01; P<0.001). Over median of 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure hospitalization events. RV dysfunction was associated with a greater risk of mortality (eg, pulmonary artery pulsatility index:hazard ratio, 1.11 per 1-SD increase [95% CI, 1.04-1.18]), with similar associations with risk of heart failure hospitalization. Body mass index modified the effect of RV dysfunction on all-cause mortality (Pinteraction≤0.005 for PAPi and RA:PCWP ratio), such that the effect of RV dysfunction was more pronounced at higher body mass index. CONCLUSIONS: Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and heart failure hospitalization, this association was especially pronounced among individuals with higher body mass index.

Identifying high risk clinical phenogroups of pulmonary hypertension through a clustering analysis.

INTRODUCTION: The classification and management of pulmonary hypertension (PH) is challenging due to clinical heterogeneity of patients. We sought to identify distinct multimorbid phenogroups of patients with PH that are at particularly high-risk for adverse events. METHODS: A hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant, or valvular surgery. K-prototypes was used to cluster patients into phenogroups based on 12 clinical covariates. RESULTS: Among 5208 patients with mean age 64±12 years, 39% women, we identified 5 distinct multimorbid PH phenogroups with similar hemodynamic measures yet differing clinical outcomes: (1) "young men with obesity", (2) "women with hypertension", (3) "men with overweight", (4) "men with cardiometabolic and cardiovascular disease", and (5) "men with structural heart disease and atrial fibrillation." Over a median follow-up of 6.3 years, we observed 2182 deaths and 2002 major cardiovascular events (MACE). In age- and sex-adjusted analyses, phenogroups 4 and 5 had higher risk of MACE (HR 1.68, 95% CI 1.41-2.00 and HR 1.52, 95% CI 1.24-1.87, respectively, compared to the lowest risk phenogroup 1). Phenogroup 4 had the highest risk of mortality (HR 1.26, 95% CI 1.04-1.52, relative to phenogroup 1). CONCLUSIONS: Cluster-based analyses identify patients with PH and specific comorbid cardiometabolic and cardiovascular disease burden that are at highest risk for adverse clinical outcomes. Interestingly, cardiopulmonary hemodynamics were similar across phenogroups, highlighting the importance of multimorbidity on clinical trajectory. Further studies are needed to better understand comorbid heterogeneity among patients with PH.

Operative Teaching of Coronary Bypass and Need for Repeat Catheterization: Does it Matter Who is Sewing?

OBJECTIVE: There are no studies to date comparing the patency of coronary bypass grafts constructed by attending surgeons versus trainees and the potential consequences of any such disparities. We explored this issue by comparing the patency of individual anastomoses performed by residents versus the attending surgeon. DESIGN: We reviewed 765 continuous cases performed by a single surgeon which involved at least 1 coronary bypass anastomosis, totaling 2,173 distal anastomoses. At a median follow-up time of 36 months (interquartile range 20.5-47.3), 83 (10.9%) patients had undergone 110 cardiac catheterization procedures after their original operation for various indications. This angiographic information provided the data for our comparison cohorts. SETTING: Cardiac surgery practice within an academic setting PARTICIPANTS: Adult patient undergoing coronary bypass grafting RESULTS: Of the 83 patients that underwent repeat catheterization, 23 (27.7%) were resident cases, 25 (30.1%) were attending cases and 35 (42.2%) were mixed. There were 4/83 (4.8%) patients with angiographic evidence of internal mammary artery graft compromise of which 3/4 (75%) had been constructed by the attending surgeon. Angiographic evidence of saphenous vein graft compromise was appreciated in 16/83 (19.3%) patients of which 9/16 (56.3%) of the grafts were constructed by the attending surgeon. CONCLUSIONS: Liberal involvement of surgical trainees as primary operators in coronary revascularization cases led to equivalent rates of postoperative ischemic complications between the attending and resident groups. The outcome equivalence was also maintained when evaluated at the individual anastomosis patency level between the 2 groups. We conclude that academic programs should continue providing trainees significant experience as primary operating surgeons without fear of clinical outcome compromise.

ECG-guided non-invasive estimation of pulmonary congestion in patients with heart failure.

Quantifying hemodynamic severity in patients with heart failure (HF) is an integral part of clinical care. A key indicator of hemodynamic severity is the mean Pulmonary Capillary Wedge Pressure (mPCWP), which is ideally measured invasively. Accurate non-invasive estimates of the mPCWP in patients with heart failure would help identify individuals at the greatest risk of a HF exacerbation. We developed a deep learning model, HFNet, that uses the 12-lead electrocardiogram (ECG) together with age and sex to identify when the mPCWP > 18 mmHg in patients who have a prior diagnosis of HF. The model was developed using retrospective data from the Massachusetts General Hospital and evaluated on both an internal test set and an independent external validation set, from another institution. We developed an uncertainty score that identifies when model performance is likely to be poor, thereby helping clinicians gauge when to trust a given model prediction. HFNet AUROC for the task of estimating mPCWP > 18 mmHg was 0.8 [Formula: see text] 0.01 and 0.[Formula: see text] 0.01 on the internal and external datasets, respectively. The AUROC on predictions with the highest uncertainty are 0.50 [Formula: see text] 0.02 (internal) and 0.[Formula: see text] 0.04 (external), while the AUROC on predictions with the lowest uncertainty were 0.86 ± 0.01 (internal) and 0.82 ± 0.01 (external). Using estimates of the prevalence of mPCWP > 18 mmHg in patients with reduced ventricular function, and a decision threshold corresponding to an 80% sensitivity, the calculated positive predictive value (PPV) is 0.[Formula: see text] 0.01when the corresponding chest x-ray (CXR) is consistent with interstitial edema HF. When the CXR is not consistent with interstitial edema, the estimated PPV is 0.[Formula: see text] 0.02, again at an 80% sensitivity threshold. HFNet can accurately predict elevated mPCWP in patients with HF using the 12-lead ECG and age/sex. The method also identifies cohorts in which the model is more/less likely to produce accurate outputs.

Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction.

Introduction: Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear. Methods: We examined patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction [pulmonary artery pulsatility index (PAPi), right atrial pressure: pulmonary capillary wedge pressure ratio (RAP:PCWP), RV stroke work index (RVSWI)]. Cox models were used to examine the association of RV function measures with clinical outcomes. Results: Among 8285 patients (mean age 63 years, 40% women), higher BMI was associated with worse indices of RV dysfunction, including lower PAPi (ß -0.26, SE 0.01, p <0.001), higher RA:PCWP ratio (ß 0.25, SE 0.01, p-value <0.001), and lower RVSWI (ß -0.05, SE 0.01, p-value <0.001). Over 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure (HF) hospitalization events. RV dysfunction was associated with greater risk of mortality (eg PAPi: HR 1.11 per 1-SD increase, 95% CI 1.04-1.18), with similar associations with risk of HF hospitalization. BMI modified the effect of RV dysfunction on outcomes (P-interaction <=0.005 for both), such that the effect of RV dysfunction was more pronounced at higher BMI. Conclusions: Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and HF hospitalization, this association was especially pronounced among individuals with higher BMI.

Association of Pulmonary Artery Pulsatility Index With Adverse Cardiovascular Events Across a Hospital-Based Sample.

BACKGROUND: The pulmonary artery pulsatility index (PAPi), calculated from the ratio of the pulmonary artery pulse pressure to right atrial pressure, is a predictor of right ventricular failure after inferior myocardial infarction and left ventricular assist device implantation. Whether PAPi is associated with adverse outcomes across a heterogeneous population is unknown. METHODS: We examined consecutive patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Multivariable Cox models were utilized to examine the association between PAPi and all-cause mortality, major adverse cardiac events, and heart failure hospitalizations. RESULTS: We studied 8285 individuals (mean age 63 years, 39% women) with median PAPi across quartiles 1.7, 2.8, 4.2, and 8.7, who were followed over a mean follow-up of 6.7±3.3 years. Patients in the lowest PAPi quartile had a 60% greater risk of death compared with the highest quartile (multivariable-adjusted hazard ratio, 1.60 [95% CI, 1.36-1.88], P<0.001) and a higher risk of major adverse cardiac events and heart failure hospitalizations (hazard ratio, 1.80 [95% CI, 1.56-2.07], P<0.001 and hazard ratio, 2.08 [95% CI, 1.76-2.47], P<0.001, respectively). Of note, patients in quartiles 2 and 3 also had increased risk of cardiovascular events compared with quartile 4 (multivariable P<0.05 for all). CONCLUSIONS: Compared with the highest PAPi quartile, patients in PAPi quartiles 1 to 3 had a greater risk of all-cause mortality, major adverse cardiac events, and heart failure hospitalizations, with greatest risk observed in the lowest quartile. A low PAPi, even at values higher than previously reported, may serve an important role in identifying high-risk individuals across a broad spectrum of cardiovascular disease.

Patient and Provider Risk in Managing ST-Elevation Myocardial Infarction During the COVID-19 Pandemic: A Decision Analysis.

BACKGROUND: The optimal treatment strategy for treating ST-segment-elevation myocardial infarction (STEMI) in context of the coronavirus disease 2019 (COVID-19) pandemic is unclear given the potential risk of occupational exposure during primary percutaneous coronary intervention (PPCI). We quantified the impact of different STEMI treatment strategies on patient outcomes and provider risk in context of the COVID-19 pandemic. METHODS: Using a decision-analytic framework, we evaluated the effect of PPCI versus the pharmaco-invasive strategy for managing STEMI on 30-day patient mortality and individual provider infection risk based on presence of cardiogenic shock, suspected coronary territory, and presence of known or presumptive COVID-19 infection. RESULTS: For patients with low suspicion for COVID-19, PPCI had mortality benefit over the pharmaco-invasive strategy, and the risk of cardiac catheterization laboratory provider infection remained very low (<0.25%) across all subgroups. For patients with presumptive COVID-19 with cardiogenic shock, PPCI offered substantial mortality benefit to patients relative to the pharmaco-invasive strategy (7.9% absolute decrease in 30-day mortality), but also greater risk of provider infection (2.3% absolute increase in risk of provider infection). For patients with presumptive COVID-19 with nonanterior STEMI without cardiogenic shock, PPCI offered a 0.4% absolute mortality benefit over the pharmaco-invasive strategy with a 0.2% greater absolute risk of provider infection, and the tradeoff between patient and provider risk with PPCI became more apparent in sensitivity analysis with more severe COVID-19 infections. CONCLUSIONS: Usual care with PPCI remains the appropriate treatment strategy in the majority of cases presenting with STEMI in the setting of the COVID-19 pandemic. However, utilization of a pharmaco-invasive strategy in selected patients with STEMI with presumptive COVID-19 and low likelihood of mortality from STEMI and use of preventive strategies such as preprocedural intubation in high risk patients when PPCI is the preferred strategy may be reasonable to reduce provider risk of COVID-19 infection.

Multidisciplinary Heart Team Approach for Complex Coronary Artery Disease: Single Center Clinical Presentation.

Background The Heart Team approach is ascribed a Class I recommendation in contemporary guidelines for revascularization of complex coronary artery disease. However, limited data are available regarding the decision-making and outcomes of patients based on this strategy. Methods and Results One hundred sixty-six high-risk coronary artery disease patients underwent Heart Team evaluation at a single institution between January 2015 and November 2018. We prospectively collected data on demographics, symptoms, Society of Thoracic Surgeons Predicted Risk of Mortality/Synergy Between PCI with Taxus and Cardiac Surgery (STS-PROM/SYNTAX) scores, mode of revascularization, and outcomes. Mean age was 70.0 years; 122 (73.5%) patients were male. Prevalent comorbidities included diabetes mellitus (51.8%), peripheral artery disease (38.6%), atrial fibrillation (27.1%), end-stage renal disease on dialysis (13.3%), and chronic obstructive pulmonary disease (21.7%). Eighty-seven (52.4%) patients had New York Heart Association III-IV and 112 (67.5%) had Canadian Cardiovascular Society III-IV symptomatology. Sixty-seven (40.4%) patients had left main and 118 (71.1%) had 3-vessel coronary artery disease. The median STS-PROM was 3.6% (interquartile range 1.9, 8.0) and SYNTAX score was 26 (interquartile range 20, 34). The median number of physicians per Heart Team meeting was 6 (interquartile range 5, 8). Seventy-nine (47.6%) and 49 (29.5%) patients underwent percutaneous coronary intervention and coronary artery bypass grafting, respectively. With increasing STS-PROM (low, intermediate, high operative risk), coronary artery bypass graft was performed less often (47.9%, 18.5%, 15.2%) and optimal medical therapy was recommended more often (11.3%, 18.5%, 30.3%). There were no trends in recommendation for coronary artery bypass graft, percutaneous coronary intervention, or optimal medical therapy by SYNTAX score tertiles. In-hospital and 30-day mortality was 3.9% and 4.8%, respectively. Conclusions Integrating a multidisciplinary Heart Team into institutional practice is feasible and provides a formalized approach to evaluating complex coronary artery disease patients. The comprehensive assessment of surgical, anatomical, and other risk scores using a decision aid may guide appropriate, evidence-based management within this team-based construct.

Obesity Is Associated With Pulmonary Hypertension and Modifies Outcomes.

Background Experimental studies support a link between obesity and pulmonary hypertension (PH), yet clinical studies have been limited. This study sought to determine the association of obesity and pulmonary hemodynamic measures and mortality in PH. Methods and Results We examined patients undergoing right-sided heart catherization (2005-2016) in a hospital-based cohort. Multivariable regression models tested associations of body mass index and pulmonary vascular hemodynamics, with PH defined as mean pulmonary artery pressure >20 mm Hg, and further subclassified into precapillary, postcapillary, and mixed PH. Multivariable Cox models were used to examine the effect of PH and obesity on mortality. Among 8940 patients (mean age, 62 years; 40% women), 52% of nonobese and 69% of obese individuals had evidence of PH. Higher body mass index was independently associated with greater odds of overall PH (odds ratio, 1.34; 95% CI, 1.29-1.40; P<0.001 per 5-unit increase in body mass index) as well as each PH subtype (P<0.001 for all). Patients with PH had greater risk of mortality compared with individuals without PH regardless of subgroup (P<0.001 for all). We found that obesity was associated with 23% lower hazard of mortality among patients with PH (hazard ratio, 0.77; 95% CI, 0.69-0.85; P<0.001). The effect of obesity was greatest among those with precapillary PH (hazard ratio, 0.57; 95% CI, 0.46-0.70; P<0.001), where obesity modified the effect of PH on mortality (P for interaction=0.02). Conclusions Obesity is independently associated with PH. PH is associated with greater mortality; this is modified by obesity such that obese patients with precapillary PH have lower mortality compared with nonobese counterparts. Further studies are needed to elucidate mechanisms underlying obesity-related PH.

Effect of Residual Interatrial Shunt on Migraine Burden After Transcatheter Closure of Patent Foramen Ovale.

OBJECTIVES: This study sought to evaluate the long-term effect of transcatheter patent foramen ovale (PFO) closure on migraineurs with and without aura and examine the effect of residual right-to-left shunt. BACKGROUND: Many studies reported improvement in migraine symptoms after PFO closure, yet randomized trials failed to reach its clinical endpoints. METHODS: The study retrospectively analyzed data from 474 patients who underwent transcatheter PFO closure at Massachusetts General Hospital. Patients completed a migraine burden questionnaire at baseline and at follow-up. Migraine severity is reported as migraine frequency (days/month), average duration (min), and migraine burden (days × min/month). Improvement following closure was defined as complete abolishment of symptoms or >50% reduction in migraine burden. RESULTS: A total of 110 migraineurs who underwent PFO closure were included; 77.0% had aura and 23.0% were without aura, and 91.0% had a cryptogenic stroke. During long-term median follow-up of 3.2 (interquartile range: 2.1 to 4.9) years, there was a significant improvement in migraine symptoms in migraineurs with or without aura. Migraine burden was reduced by >50% in 87.0% of patients, and symptoms were completely abolished in 48%. Presence of aura was associated with abolishment of migraine (odds ratio: 4.30; 95% confidence interval: 1.50 to 12.30; p = 0.006). At 6 months after PFO closure, residual right-to-left shunt was present in 26% of patients. Absence of right-to-left shunt was associated with improvement in migraine burden by >50% (odds ratio: 4.60; 95% confidence interval: 1.30 to 16.10; p = 0.017). CONCLUSIONS: Long-term follow-up after transcatheter PFO closure was associated with significant improvement in migraine burden. Aura was a predictor of abolishing symptoms. Absence of residual right-to-left shunt was a predictor of significant reduction in migraine burden.

In-hospital outcomes in invasively managed acute myocardial infarction patients who receive morphine.

OBJECTIVE: We aimed to analyze the association between morphine and in-hospital outcomes in invasively managed ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) patients. BACKGROUND: Morphine is commonly used for analgesia in the setting of acute coronary syndromes (ACS); however, recently its utility in ACS has come under closer scrutiny. METHODS: We identified all STEMI and NSTE-ACS patients undergoing coronary angiogram +/- percutaneous intervention between January 2009 and July 2016 in our center and recorded patient characteristics and inpatient outcomes. RESULTS: Overall, 3027 patients were examined. Overall, STEMI patients who received morphine had no difference in in-hospital mortality [4.18% vs. 7.54%, odds ratio (OR): 0.36, P = 0.19], infarct size (mean troponin level 0.75 ng/mL vs. 1.29 ng/mL, P = 0.32) or length of hospital stay (P = 0.61). The NSTE-ACS patients who received morphine had a longer hospital stay (mean 6.58 days vs. 4.78 days, P < 0.0001) and larger infarct size (mean troponin 1.16 ng/mL vs. 0.90 ng/mL, P = 0.02). Comparing matched patients, the use of morphine was associated with larger infarct size (mean troponin 1.14 ± 1.92 ng/mL vs. 0.83 ± 1.49 ng/mL, P = 0.01), longer hospital stay (6.5 ± 6.82 days vs. 4.89 ± 5.36 days, P = 0.004) and a trend towards increased mortality (5% vs. 2%, OR: 2.55, P = 0.06) in NSTE-ACS patients but morphine did not affect outcomes in the propensity matched STEMI patients. CONCLUSION: In a large retrospective study, morphine was associated with larger infarct size, a longer hospital stay and a trend towards increased mortality in invasively managed NSTE-ACS patients even after adjustment for clinical characteristics.

Non-diagnostic coronary artery calcification and stenosis: a correlation of coronary computed tomography angiography and invasive coronary angiography.

Background Heavy coronary artery calcification (CAC) impairs diagnostic accuracy of coronary computed tomography angiography (cCTA) and is considered to be a major limitation. Purpose To investigate the effect of non-evaluable CAC seen on cCTA on clinical decision-making by determining the degree of subsequent invasive testing and to assess the relationship between non-evaluable segments containing CAC and significant stenosis as seen in invasive coronary angiography (ICA). Material and Methods The study comprised of 356 patients who underwent cCTA and subsequent ICA within 2 months between 2005 and 2009. Clinical reports were reviewed to identify the indications for referral to ICA. In a subset of 68 patients where non-diagnostic CAC on cCTA and significant stenosis on ICA were present in the same segment, we correlated and analyzed the underlying stenosis severity of the lesion on ICA to the cCTA. Lesions with CAC were analyzed in a standardized fashion by application of reading rules. Results Non-diagnostic CAC on cCTA prompted ICA in 5.6% of patients. CAC occurred at the site of maximum stenosis in segments with stenosis <50% (95.9% [47/49]), 50-69% (82.4% [28/34]), 70-99% (64.5% [31/48]), and 100% (33.3% [1/3]). At the point of maximum calcium deposit, non-obstructive disease was present in 61.2%. Application of reading rules resulted in a 44% reduction in non-diagnostic cCTA reads. Conclusion Severe CAC may prompt further investigation with ICA. There is less CAC with increasing lesion severity at the point of maximum stenosis. Additional application of reading rules improved non-diagnostic cCTA reads.

Metabolite Profiles Predict Acute Kidney Injury and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute kidney injury (AKI) occurs commonly after transcatheter aortic valve replacement (TAVR) and is associated with markedly increased postoperative mortality. We previously identified plasma metabolites predictive of incident chronic kidney disease, but whether metabolite profiles can identify those at risk of AKI is unknown. METHODS AND RESULTS: We performed liquid chromatography-mass spectrometry-based metabolite profiling on plasma from patients undergoing TAVR and subjects from the community-based Framingham Heart Study (N=2164). AKI was defined by using the Valve Academic Research Consortium-2 criteria. Of 44 patients (mean age 82±9 years, 52% female) undergoing TAVR, 22 (50%) had chronic kidney disease and 9 (20%) developed AKI. Of 85 metabolites profiled, we detected markedly concordant cross-sectional metabolic changes associated with chronic kidney disease in the hospital-based TAVR and Framingham Heart Study cohorts. Baseline levels of 5-adenosylhomocysteine predicted AKI after TAVR, despite adjustment for baseline glomerular filtration rate (odds ratio per 1-SD increase 5.97, 95% CI 1.62-22.0; P=0.007). Of the patients who had AKI, 6 (66.7%) subsequently died, compared with 3 (8.6%) deaths among those patients who did not develop AKI (P=0.0008) over a median follow-up of 7.8 months. 5-adenosylhomocysteine was predictive of all-cause mortality after TAVR (hazard ratio per 1-SD increase 2.96, 95% CI 1.33-6.58; P=0.008), independent of baseline glomerular filtration rate. CONCLUSIONS: In an elderly population with severe aortic stenosis undergoing TAVR, metabolite profiling improves the prediction of AKI. Given the multifactorial nature of AKI after TAVR, metabolite profiles may identify those patients with reduced renal reserve.

Angina Severity, Depression, and Response to Percutaneous Revascularization in Patients With Chronic Total Occlusion of Coronary Arteries.

OBJECTIVES: This study sought to quantify depression rates in patients referred for percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), assess its relationship to baseline angina symptoms, and compare angina improvement after CTO-PCI between depressed and non-depressed patients. BACKGROUND: Depression is common among patients with chronic angina, and portends poor prognosis. CTOs are a common cause of angina. The relationships between angina, depression, and CTO intervention are unknown. METHODS: We collected baseline and 30-day post-PCI data on angina (Seattle Angina Questionnaire [SAQ7]), dyspnea (Rose Dyspnea Scale [RDS]), and depression status (Patient Health Questionnaire [PHQ-2]) on 45 consecutive patients referred for CTO-PCI between October 2013 and October 2014. RESULTS: Depression (PHQ-2 score ≥3) was present in 18/45 patients (40%) at baseline. Baseline SAQ7 Summary and SAQ7 Angina Frequency scores for depressed patients were 35.4 (range, 28.4-42.4) and 54.4 (range, 43.0-65.8), compared with 67.3 (range, 57.5-77.1) and 77.8 (range, 68.5-87.1) for non-depressed patients (P<.001 and P=.01, respectively). Following CTO-PCI, the mean improvement in SAQ7 Summary and SAQ7 Angina Frequency scores was 48.5 (range, 35.4-61.5) and 32.8 (range, 21.0-44.5) for patients with depression, compared with 16.5 (range, 5.87-27.2) and 12.6 (range, 3.0-22.2) for patients without depression (P<.001 and P=.01, respectively). Following PCI, the presence of depression was reduced (72% relative reduction vs. baseline; P=.01). CONCLUSIONS: Depression identifies patients more limited by angina and more likely to respond to CTO-PCI compared with non-depressed patients. Depression screening may be indicated for patients with CTO, as 67% of CTO patients were not receiving treatment for depression.

Feasibility of a Tablet Computer System to Collect Patient-reported Symptom Severity in Patients Undergoing Diagnostic Coronary Angiography.

BACKGROUND: Percutaneous coronary intervention is the most commonly performed revascularization modality for chronic stable angina, but does not improve survival or reduce major adverse cardiovascular event. Percutaneous coronary intervention in this population is performed primarily for symptomatic benefit; therefore, symptom reduction is an important marker of quality. Patient-reported outcome measures (PROMs) have been developed for chest pain and dyspnea which are valid and responsive to treatment; however, they are not widely used in routine care. We present a model for use of PROMs in routine care. METHODS: Partners Health System funded a tablet computer software platform to collect PROMs and include them in the medical record. We implemented this platform in the catheterization laboratory at Massachusetts General Hospital, targeting patients presenting for coronary angiography. Patients are assessed using the SAQ-7, the Rose dyspnea scale, the PHQ-2, and the PROMIS-10. We used a phased implementation, with the final program including preprocedure measurement, presentation of data to clinical providers, and follow up using an email platform. RESULTS: We successfully captured measures from 474 patients, 53.5% of outpatient visits. Key success factors included high-level leadership support and resources, a user-friendly interface for patients and staff, easily interpretable measures, and clinical relevance. CONCLUSIONS: We have demonstrated that routine capture of patient-reported symptom severity is technically feasible in a real-world care environment. We share our experiences to provide others with a model for similar programs, and to accelerate implementation nationwide by helping others avoid pitfalls. We believe expansion of similar programs nationally may lead to more robust quality infrastructure.

Differences Among Cardiologists in Rates of Positive Coronary Angiograms.

BACKGROUND: Understanding the sources of variation for high-cost services has the potential to improve both patient outcomes and value in health care delivery. Nationally, the overall diagnostic yield of coronary angiography is relatively low, suggesting overutilization. Understanding how individual cardiologists request catheterization may suggest opportunities for improving quality and value. We aimed to assess and explain variation in positive angiograms among referring cardiologists. METHODS AND RESULTS: We identified all cases of diagnostic coronary angiography at Massachusetts General Hospital from January 1, 2012, to June 30, 2013. We excluded angiograms for acute coronary syndrome. For each angiogram, we identified clinical features of the patients and characteristics of the requesting cardiologists. We also identified angiogram positivity, defined as at least 1 epicardial coronary stenosis ≥50% luminal narrowing. We then constructed a series of mixed-effects logistic regression models to analyze predictors of positive coronary angiograms. We assessed variation by physician in the models with median odds ratios. Over this time period, 5015 angiograms were identified. We excluded angiograms ordered by cardiologists requesting <10 angiograms. Among the remaining 2925 angiograms, 1450 (49.6%) were positive. Significant predictors of positive angiograms included age, male patients, and peripheral arterial disease. After adjustment for clinical variables only, the median odds ratio was 1.23 (95% CI 1.0-1.36), consistent with only borderline clinical variation after adjustment. In the full clinical and nonclinical model, the median odds ratio was 1.07 (95% CI 1.07-1.20), also consistent with clinically insignificant variation. CONCLUSIONS: Substantial variation exists among requesting cardiologists with respect to positive and negative coronary angiograms. After adjustment for clinical variables, there was only borderline clinically significant variation. These results emphasize the importance of risk adjustment in reporting related to quality and value.

Predicting the Presence of an Acute Coronary Lesion Among Patients Resuscitated From Cardiac Arrest.

BACKGROUND: A mechanism to stratify patients resuscitated from a cardiac arrest according to the likelihood of an acute coronary lesion would have significant utility. We thus sought to develop and validate a risk prediction model for the presence of an acute coronary lesion among patients resuscitated from an arrest. METHODS AND RESULTS: All subjects undergoing coronary angiography after resuscitation from a cardiac arrest were identified in an ongoing institutional registry from 2009 to 2014. Backwards stepwise selection of candidate covariates was used to create a logistic regression model for the presence of an angiographic culprit lesion and internally validated with bootstrapping. A clinical point score was generated and its prognostic abilities compared with contemporary measures. Among 247 subjects undergoing coronary angiography after resuscitation from a cardiac arrest, 130 (52%) had an acute lesion in a coronary artery. A multivariable model-including angina, congestive heart failure symptoms, shockable arrest rhythm (ventricular fibrillation/ventricular tachycardia), and ST-elevations-had excellent discrimination (optimism corrected C-Statistic, 0.88) and calibration (Hosmer-Lemeshow P=0.540) for an acute coronary lesion. Compared with electrocardiographic findings alone, a point score based on this model more accurately predicted the presence of an acute lesion among patients resuscitated from a cardiac arrest (integrated discrimination improvement, 0.10; 95% confidence interval, 0.04-0.19; P<0.001). CONCLUSIONS: Patients with a cardiac arrest can be risk stratified for the presence of an acute coronary lesion using 4 easily measured variables. This simple risk score may be used to improve patient selection for emergent coronary angiography among resuscitated patients.