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This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF).In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood.We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population.In HFpEF, only age (standardized beta = 0.593; P 0.001), exercise stroke volume (standardized beta = 0.349; P 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004).In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome.

Mechanisms underlying sex differences in heart failure with preserved ejection fraction (HFpEF) are poorly understood. We sought to examine sex differences in measures of arterial stiffness and the association of arterial stiffness measures with left ventricular hemodynamic responses to exercise in men and women.We studied 83 men (mean age 62 years) and 107 women (mean age 59 years) with HFpEF who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial stiffness measurement (augmentation pressure [AP], augmentation index [AIx], and aortic pulse pressure [AoPP]). Sex differences were compared using multivariable linear regression. We examined the association of arterial stiffness with abnormal left ventricular diastolic response to exercise, defined as a rise in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO) ≥ 2 mmHg/L/min by using logistic regression models.Women with HFpEF had increased arterial stiffness compared with men. AP was nearly 10 mmHg higher, and AIx was more than 10% higher in women compared with men (P0.0001 for both). Arterial stiffness measures were associated with a greater pulmonary capillary wedge pressure response to exercise, particularly among women. A 1-standard deviation higher AP was associated with3-fold increased odds of abnormal diastolic exercise response (AP: OR 3.16, 95% CI 1.34-7.42; P = 0.008 [women] vs OR 2.07, 95% CI 0.95-5.49; P = 0.15 [men]) with similar findings for AIx and AoPP.Arterial stiffness measures are significantly higher in women with HFpEF than in men and are associated with abnormally steep increases in pulmonary capillary wedge pressure with exercise, particularly in women. Arterial stiffness may preferentially contribute to abnormal diastolic function during exercise in women with HFpEF compared with men.

A 25-year-old woman with severe tricuspid valve endocarditis and septic pulmonary emboli required VA-ECMO for recurrent hypoxemia-induced cardiac arrest. We present the clinical challenges requiring ECMO circuit reconfiguration and a percutaneous approach for vegetation debulking. (Level of Difficulty: Intermediate.), Central Illustration

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 P P P 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.

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Background Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. Objectives This study sought to investigate the association of exPH with clinical determinants and outcomes. Methods The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. Results Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p Conclusions Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.

This report presents the case of this atypical presentation of a rare disease in a 19-year-old female with cardiomyopathy and hypertension. Investigation revealed renovascular stenosis, infarcts, and active vasculitis pathognomonic for Takayasu arteritis (TA). Cardiac magnetic resonance imaging demonstrated mild pericardial inflammation and epicardial edema. Vasculitis-induced renovascular secondary hypertension resulted in myocardial dysfunction, which recovered with treatment of hypertension and TA. (Level of Difficulty: Beginner.), Graphical abstract, This report presents the case of this atypical presentation of a rare disease in a 19-year-old female with cardiomyopathy and hypertension. Investigation revealed renovascular…

BACKGROUND: Obesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear. RESEARCH QUESTION: To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance. METHOD: We examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006–June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression. RESULTS: Obesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV(1) and FVC with a preserved FEV(1)/FVC ratio suggesting a restrictive physiology pattern (P≤0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV(1) and FVC (beta −4.8, s.e. 0.9 for FEV1; beta −4.9, s.e. 0.8 for FVC; P

Introduction: The pulmonary artery pulsatility index (PAPi), calculated from the ratio of pulmonary artery pulse pressure to right atrial pressure, was initially described as a novel predictor of right ventricular failure after inferior myocardial infarction or left ventricular assist device implantation. Whether PAPi is associated with adverse outcomes in broader samples is unknown. Hypothesis: A lower PAPi is associated with mortality in a broad population referred for right heart catheterization. Methods: We examined consecutive patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. The following exclusion criteria were applied: shock or cardiac arrest within 24 hours of catheterization, presence of mechanical circulatory support, prior cardiac transplant, prior valvular surgery, or those with missing key clinical covariates. Multivariable Cox models were utilized to examine the association between PAPi and mortality. Analyses were adjusted for age, sex, BMI, hypertension, diabetes, prior myocardial infarction, and prior heart failure. Results: We studied 8559 patients with mean age 63 years and 40% women. We found that patients in the lowest quartile of PAPi were younger, with greater proportion of men, and higher BMI, yet similar NT-proBNP compared with other quartiles ( Table 1 ). Over 12.5 years of follow-up, there were 2441 death events. Patients in the lowest PAPi quartile had a 31% greater risk of death compared with the highest quartile (multivariable adjusted HR 1.31, 95% CI 1.15-1.48, p0.05 vs quartile 4 for both). Conclusions: Patients in the lowest PAPi quartile had a 31% increased risk of all-cause mortality in a broad population referred for right heart catheterization. These findings highlight a potential role for PAPi in identifying high-risk individuals across a spectrum of disease.

Arterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise.A total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52-3.05; P.001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption.Exercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular-vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.

Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg -1 ·min -1 (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication. Conclusions: Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions.

STUDY DESIGN A prospective cohort. OBJECTIVE The aim of this study was to prospectively observe donor site pain, health-related quality-of-life outcomes, and complications following harvest of tricortical anterior iliac crest bone graft (AICBG) for anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA Persistent donor site pain from the anterior iliac crest has been reported to range between 2% and 40%. This morbidity has led surgeons to consider interbody alternatives for ACDF, which carry additional costs. METHODS We prospectively enrolled 50 patients from 2 tertiary care centers over the course of 1 year observing complications and patient-reported outcomes. Patients filled out SF-12 and numeric rating scale (NRS) for pain in the arm, neck, and donor site pre-operatively and at 1 week, 2 weeks, 6 weeks, 3 to 6 months, and 1 year postoperatively. Outcomes were compared with a control group undergoing ACDF with allograft or Polyether ether ketone cages at 1 year. RESULTS The mean ± SD donor site pain at 1 week was 5.6 ± 2.8 but decreased to 2.2 ± 2.4 at 6 weeks and 1.1 ± 1.8 at 1 year (P

Acute pulmonary embolism (PE) is a common cardiovascular condition resulting in significant morbidity and mortality. Consensus recommendations suggest risk stratification of patients into three main categories: high-risk or 'massive' PE, intermediate-risk or 'submassive' PE, and low-risk PE. Given the relative dearth of prospective, randomized clinical trials delineating optimal selection of the diverse medical, interventional, and surgical treatment approaches, clinical care requires a multidisciplinary expert approach to patients with PE. Areas covered: The Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) was the first of its kind to create a multidisciplinary, rapid response team for acute PE, integrated within a research and educational framework. The MGH PERT has treated more than 700 patients with PE, the majority of which are in the 'massive' or 'submassive' categories. The PERT Consortium™ was founded in 2015 as a collaborative network between the growing number of PERT programs internationally, with greater than 80 institutions participating within one year of establishment. Expert commentary: Since its advent, the PERT model has expanded throughout the United States and internationally through a collaborative institutional and research network. PERT may represent a new standard for the care of patients with acute PE.

Introduction: Chronic cardiac conditions, such as heart failure (HF) and atrial fibrillation (AF), have complex pathophysiology that can often pose challenges when treating comorbid conditions, especially with respect to drug-disease interactions. Although much is known scientifically about these interactions, integrating such evidence into clinical practice with the intent of avoiding negative health outcomes and avoiding excess healthcare costs has proved challenging. Here, we present: (1) a novel software platform that enables real-time assessment of incidence of drug-disease interactions among patients with CHF taking medications for other comorbid indications in a large cohort; and (2) development of a natural language processing (NLP)-driven software platform for performing such quality improvement assessments through automated searches of the electronic health record (EHR) of patients with any cardiac disease. Methods and Results: An NLP-driven search tool (Figure 1A) was developed based upon the Queriable Patient Inference Dossier (QPID) created by the Laboratory of Computer Science at the Massachusetts General Hospital (MGH) that incorporates an automated assessment of chronic cardiac diseases and of medications that have been identified as absolutely or relatively contraindicated in patients with specific cardiac diseases. The tool, which can be customized to assess for medications or other factors important in cardiovascular care, was used to perform an automated cross-sectional study of medications prescribed to 2,500 patients with CHF currently under care at the MGH. All records were manually reviewed by two independent observers, with a Cohen’s κ of greater than 0.8. Nearly 60% of patients were prescribed agents in the past three months that are known to cause major or moderate adverse events, with three drugs (citalopram, doxazosin and ibuprofen), accounting for over 80% of the contraindicated agents (Figure 1B). Conclusion: Use of prescription drugs known to cause major or moderate adverse events among patients with HF is quite common. An automated software platform for rapid real-time assessment of drug disease interactions can help identify gaps in care and help improve the quality of care among patients with cardiovascular disease and multiple comorbidities.

Palliative care (PC) services are integral to the care of patients with advanced medical illnesses. Given the significant morbidity and mortality associated with cardiac arrest, we sought to measure the use and impact of PC in the care of patients treated with therapeutic hypothermia (TH).We conducted a retrospective study of 317 consecutive patients undergoing TH after cardiac arrest. We compared intensive care unit (ICU) characteristics and clinical outcomes of subjects who received PC consultation (n=125) to those who did not (n=192).The proportion of TH patients with PC consultations increased to greater than 60% by 2013, corresponding to our institution's expansion of PC services, development of a dedicated PC unit, and integration of this service into our published TH protocol. In the TH population, time to return of spontaneous circulation (ROSC) was associated with higher inpatient mortality (p0.001) and placement of a PC consult (p=0.011). TH patients who received PC consultation had longer ICU stays (p=0.034), more ventilator days (p0.001), and higher inpatient mortality (p0.001). When these measures were analyzed cohort-wide comparing all TH patients pre- and post-2013, at which time the frequency of PC consultation had dramatically increased, there were no statistically significant differences in ICU care or outcomes.In our population of cardiac arrest patients undergoing TH, the utilization of PC services has increased over time, particularly for those patients with high morbidity and mortality. Future randomized studies may further delineate optimal patient selection for PC consultation to better facilitate goals of care discussions and timely medical decision-making.

Background: Palliative care (PC) is integral in the care of patients with advanced medical illnesses. The significant morbidity and mortality associated with therapeutic hypothermia (TH) after cardiac arrest calls for improved end-of-life care. The goal of this descriptive study was to review our institutional experience with PC consultation in this critically ill population. Methods: We conducted a retrospective study of 319 consecutive patients undergoing TH post-cardiac arrest at Vanderbilt University Medical Center from May 2007 to April 2014. We compared intensive care unit characteristics of patients who received PC consultation (n=125) to those who did not (n=194). We performed Wilcoxon rank sum analyses for time on mechanical ventilation and vasopressor support and Pearson chi-square analyses for inpatient mortality, placement of a Do Not Resuscitate (DNR) order and withdrawal of life support. Results: The number of TH patients and PC consultations in this population increased over time (Figure 1). In the overall cohort, the mean age was 57.3 years (+/- 15.3), and 61% of patients were male. The PC group was mechanically ventilated longer (mean 5.18 vs. 3.45 days, p Conclusions: In our TH population, PC consultation increased over time, corresponding to our institution’s expansion of staffing, opening of a PC unit and integration of this service into our published TH protocol. Future studies may delineate the appropriate patient selection for PC consultation to better facilitate goals of care and medical decision-making.

Introduction: The effects of hypothermia on hemostatic function are complex and poorly understood. While cardiac arrest and CPR can elicit a pro-inflammatory, pro-coagulant state, hypothermia may alter platelet count, activation and aggregation. Hypothesis: We hypothesized that treatment with systemic heparin during therapeutic hypothermia (TH) is associated with improved neurologic outcomes. Methods: We conducted a retrospective study of 157 cardiac arrest survivors treated with TH at our institution from 2007-2014. A priori, we excluded TH patients (pts) presenting with an acute coronary syndrome requiring percutaneous coronary intervention, pulmonary embolus, venous thrombosis or need for mechanical circulatory support. We used a multivariable logistic regression model to examine the relationship between systemic heparin and neurologic outcome (Cerebral Performance Category score 1-2=good; 3-5=poor) as well as inpatient survival. We also performed a chi-square analysis for the secondary endpoint of major bleeding. Results: Mean age was 57.0 (+/- 16.2) years; 86 (54%) pts were male; and 75 (47.8%) pts had an initial rhythm of ventricular tachycardia or ventricular fibrillation. At discharge, 48 (30.6%) pts had a good neurologic outcome and 23 (14.7%) pts suffered from a major bleed. Systemic heparin was administered to 48 (30.6%) pts, and was neither associated with favorable neurologic outcome (OR 0.99, CI 0.39-2.56, p=0.991) nor inpatient survival (OR 1.28, CI 0.54-3.05, p=0.574). The risk of bleeding with heparin was 2.08 (CI 0.99-4.38, p=0.052). Conclusions: In our cohort, indiscriminate use of systemic heparin during TH post-cardiac arrest was not associated with improved neurologic outcomes. Conversely, a trend towards increased risk of major bleeding was noted.

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function.