Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

BACKGROUND: While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance. METHODS: We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves. RESULTS: On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48-0.54 versus 0.38) and peak VO2 percentage predicted (0.23-0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO2 <50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11-0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16-0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53-1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082). CONCLUSIONS: In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.

Cardiopulmonary Exercise Testing, Rehabilitation, and Exercise Training in Postpulmonary Embolism.

Long-term exercise intolerance and functional limitations are common after an episode of acute pulmonary embolism (PE), despite 3 to 6 months of anticoagulation. These persistent symptoms are reported in more than half of the patients with acute PE and are referred as "post-PE syndrome." Although these functional limitations can occur from persistent pulmonary vascular occlusion or pulmonary vascular remodeling, significant deconditioning can be a major contributing factor. Herein, the authors review the role of exercise testing to elucidate the mechanisms of exercise limitations to guide next steps in management and exercise training for musculoskeletal deconditioning.

Recumbent Ergometer vs Treadmill Cardiopulmonary Exercise Test in HFpEF: Implications for Chronotropic Response and Exercise Capacity.

BACKGROUND: Cardiopulmonary exercise testing (CPET) can identify mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF), but exercise modalities with differing body positions (eg, recumbent ergometer, treadmill) are broadly used. In this study, we aimed to determine whether body position affects CPET parameters in patients with HFpEF. METHODS: Subjects with stable HFpEF (n = 23) underwent noninvasive treadmill CPET, followed by an invasive recumbent-cycle ergometer CPET within 3 months. A comparison group undergoing similar studies included healthy subjects (n = 5) and subjects with pulmonary arterial hypertension (n = 6). RESULTS: The peak oxygen consumption (VO2peak) and peak heart rate were significantly lower in the recumbent vs the upright position (10.1 vs 13.1 mL/kg/min [Δ-3 mL/kg/min]; P < 0.001; and 95 vs 113 bpm [Δ-18 bpm]; P < 0.001, respectively). No significant differences were found in the minute ventilation to carbon dioxide production ratio, end-tidal pressure of carbon dioxide or respiratory exchange ratio. A similar pattern was observed in the comparison groups. CONCLUSIONS: Compared to recumbent ergometer, treadmill CPET revealed higher VO2peak and peak heart rate response. When determining chronotropic incompetence to adjust beta-blocker administration in HFpEF, body position should be taken into account.

Multimodality Deep Phenotyping Methods to Assess Mechanisms of Poor Right Ventricular-Pulmonary Artery Coupling.

Deep phenotyping of pulmonary hypertension (PH) with multimodal diagnostic exercise interventions can lead to early focused therapeutic interventions. Herein, we report methods to simultaneously assess pulmonary impedance, differential biventricular myocardial strain, and right ventricular:pulmonary arterial (RV:PA) uncoupling during exercise, which we pilot in subjects with suspected PH. As proof-of-concept, we show that four subjects with different diagnoses [pulmonary arterial hypertension (PAH); chronic thromboembolic disease (CTEPH); PH due to heart failure with preserved ejection fraction (PH-HFpEF); and noncardiac dyspnea (NCD)] have distinct patterns of response to exercise. RV:PA coupling assessment with exercise was highest-to-lowest in this order: PAH > CTEPH > PH-HFpEF > NCD. Input impedance (Z0) with exercise was highest in precapillary PH (PAH, CTEPH), followed by PH-HFpEF and NCD. Characteristic impedance (ZC) tended to decline with exercise, except for the PH-HFpEF subject (initial Zc increase at moderate workload with subsequent decrease at higher workload with augmentation in cardiac output). Differential myocardial strain was normal in PAH, CTEPH, and NCD subjects and lower in the PH-HFpEF subject in the interventricular septum. The combination of these metrics allowed novel insights into mechanisms of RV:PA uncoupling. For example, while the PH-HFpEF subject had hemodynamics comparable to the NCD subject at rest, with exercise coupling dropped precipitously, which can be attributed (by decreased myocardial strain of interventricular septum) to poor support from the left ventricle (LV). We conclude that this deep phenotyping approach may distinguish afterload sensitive vs. LV-dependent mechanisms of RV:PA uncoupling in PH, which may lead to novel therapeutically relevant insights.

Increased RV:LV ratio on chest CT-angiogram in COVID-19 is a marker of adverse outcomes.

BACKGROUND: Right ventricular (RV) dilation has been used to predict adverse outcomes in acute pulmonary conditions. It has been used to categorize the severity of novel coronavirus infection (COVID-19) infection. Our study aimed to use chest CT-angiogram (CTA) to assess if increased RV dilation, quantified as an increased RV:LV (left ventricle) ratio, is associated with adverse outcomes in the COVID-19 infection, and if it occurs out of proportion to lung parenchymal disease. RESULTS: We reviewed clinical, laboratory, and chest CTA findings in COVID-19 patients (n = 100), and two control groups: normal subjects (n = 10) and subjects with organizing pneumonia (n = 10). On a chest CTA, we measured basal dimensions of the RV and LV in a focused 4-chamber view, and dimensions of pulmonary artery (PA) and aorta (AO) at the PA bifurcation level. Among the COVID-19 cohort, a higher RV:LV ratio was correlated with adverse outcomes, defined as ICU admission, intubation, or death. In patients with adverse outcomes, the RV:LV ratio was 1.06 ± 0.10, versus 0.95 ± 0.15 in patients without adverse outcomes. Among the adverse outcomes group, compared to the control subjects with organizing pneumonia, the lung parenchymal damage was lower (22.6 ± 9.0 vs. 32.7 ± 6.6), yet the RV:LV ratio was higher (1.06 ± 0.14 vs. 0.89 ± 0.07). In ROC analysis, RV:LV ratio had an AUC = 0.707 with an optimal cutoff of RV:LV ≥ 1.1 as a predictor of adverse outcomes. In a validation cohort (n = 25), an RV:LV ≥ 1.1 as a cutoff predicted adverse outcomes with an odds ratio of 76:1. CONCLUSIONS: In COVID-19 patients, RV:LV ratio ≥ 1.1 on CTA chest is correlated with adverse outcomes. RV dilation in COVID-19 is out of proportion to parenchymal lung damage, pointing toward a vascular and/or thrombotic injury in the lungs.

Pulmonary vascular distensibility with passive leg raise is comparable to exercise and predictive of clinical outcomes in pulmonary hypertension.

Pulmonary vascular distensibility (α) is a marker of the ability of the pulmonary vasculature to dilate in response to increases in cardiac output, which protects the right ventricle from excessive increases in afterload. α measured with exercise predicts clinical outcomes in pulmonary hypertension (PH) and heart failure. In this study, we aim to determine if α measured with a passive leg raise (PLR) maneuver is comparable to α with exercise. Invasive cardiopulmonary exercise testing (iCPET) was performed with hemodynamics recorded at three stages: rest, PLR and peak exercise. Four hemodynamic phenotypes were identified (2019 ECS guidelines): pulmonary arterial hypertension (PAH) (n = 10), isolated post-capillary (Ipc-PH) (n = 18), combined pre-/post-capillary PH (Cpc-PH) (n = 15), and Control (no significant PH at rest and exercise) (n = 7). Measurements of mean pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output at each stage were used to calculate α. There was no statistical difference between α-exercise and α-PLR (0.87 ± 0.68 and 0.78 ± 0.47% per mmHg, respectively). The peak exercise- and PLR-based calculations of α among the four hemodynamic groups were: Ipc-PH = Ex: 0.94 ± 0.30, PLR: 1.00 ± 0.27% per mmHg; Cpc-PH = Ex: 0.51 ± 0.15, PLR: 0.47 ± 0.18% per mmHg; PAH = Ex: 0.39 ± 0.23, PLR: 0.34 ± 0.18% per mmHg; and the Control group: Ex: 2.13 ± 0.91, PLR: 1.45 ± 0.49% per mmHg. Patients with α ≥ 0.7% per mmHg had reduced cardiovascular death and hospital admissions at 12-month follow-up. In conclusion, α-PLR is feasible and may be equally predictive of clinical outcomes as α-exercise in patients who are unable to exercise or in programs lacking iCPET facilities.

Distinguishing exercise intolerance in early-stage pulmonary hypertension with invasive exercise hemodynamics: Rest VE /VCO2 and ETCO2 identify pulmonary vascular disease.

BACKGROUND: Among subjects with exercise intolerance and suspected early-stage pulmonary hypertension (PH), early identification of pulmonary vascular disease (PVD) with noninvasive methods is essential for prompt PH management. HYPOTHESIS: Rest gas exchange parameters (minute ventilation to carbon dioxide production ratio: VE /VCO2 and end-tidal carbon dioxide: ETCO2 ) can identify PVD in early-stage PH. METHODS: We conducted a retrospective review of 55 subjects with early-stage PH (per echocardiogram), undergoing invasive exercise hemodynamics with cardiopulmonary exercise test to distinguish exercise intolerance mechanisms. Based on the rest and exercise hemodynamics, three distinct phenotypes were defined: (1) PVD, (2) pulmonary venous hypertension, and (3) noncardiac dyspnea (no rest or exercise PH). For all tests, *p < .05 was considered statistically significant. RESULTS: The mean age was 63.3 ± 13.4 years (53% female). In the overall cohort, higher rest VE /VCO2 and lower rest ETCO2 (mm Hg) correlated with high rest and exercise pulmonary vascular resistance (PVR) (r ~ 0.5-0.6*). On receiver-operating characteristic analysis to predict PVD (vs. non-PVD) subjects with noninvasive metrics, area under the curve for pulmonary artery systolic pressure (echocardiogram) = 0.53, rest VE /VCO2 = 0.70* and ETCO2 = 0.73*. Based on this, optimal thresholds of rest VE /VCO2 > 40 mm Hg and rest ETCO2 < 30 mm Hg were applied to the overall cohort. Subjects with both abnormal gas exchange parameters (n = 12, vs. both normal parameters, n = 19) had an exercise PVR 5.2 ± 2.6* (vs. 1.9 ± 1.2), mPAP/CO slope with exercise 10.2 ± 6.0* (vs. 2.9 ± 2.0), and none included subjects from the noncardiac dyspnea group. CONCLUSIONS: In a broad cohort of subjects with suspected early-stage PH, referred for invasive exercise testing to distinguish mechanisms of exercise intolerance, rest gas exchange parameters (VE /VCO2 > 40 mm Hg and ETCO2 < 30 mm Hg) identify PVD.

National Trends in Heart Donor Usage Rates: Are We Efficiently Transplanting More Hearts?

Background It is unclear whether the recent increase in the number of heart transplants performed annually in the United States is only because of higher availability of donors and if it affected recipients' survival. Methods and Results We examined characteristics of donors and recipients from 2008 to 2012 (n=11 654) and 2013 to 2017 (n=14 556) and compared them with 2003 to 2007 (n=10 869). Cox models examined 30-day and 1-year risk of recipients' death post transplant. From 2013 to 2017, there was an increase in the number of transplanted hearts and number of donor offers but an overall decline in the ratio of hearts transplanted to available donors. Donors between 2013 and 2017 were older, heavier, more hypertensive, diabetic, and likely to have abused illicit drugs compared with previous years. Drug overdose and hepatitis C positive donors were additional contributors to donor risk in recent years. In Cox models, risk of death post transplant between 2013 and 2017 was 15% lower at 30 days (hazard ratio [HR] 0.85; 95% CI, 0.74-0.98) and 21% lower at 1 year (HR, 0.79; 95% CI, 0.73-0.87) and between 2008 and 2012 was 9% lower at 30 days (HR, 0.91; 95% CI, 0.79-1.05) and 14% lower at 1 year (HR, 0.86; 95% CI, 0.79-0.94) compared with 2003 to 2007. Conclusions Despite a substantial increase in heart donor offers in recent years, the ratio of transplants performed to available donors has decreased. Even though hearts from donors who are older, more hypertensive, and have diabetes mellitus are being used, overall recipient survival continues to improve. Broader acceptance of drug overdose and hepatitis C positive donors may increase the number and percentage of heart transplants further without jeopardizing short-term outcomes.

Patent foramen ovale and neurologic events in patients undergoing liver transplantation.

BACKGROUND: Patent foramen ovale (PFO) is present in approximately 20% of individuals. During liver transplantation (LT), intra-operative transesophageal echocardiography can observe transient intra-cardiac shunting of atheromatous debris via a PFO. Closure of PFOs prior to LT has thus been suggested as a potential treatment to reduce peri-operative cerebral vascular accident (CVA). The objective of this study was to assess if the presence of PFO is associated with CVA in patients undergoing LT. METHODS: Three hundred fifty-eight patients undergoing LT at a single academic institution were included. All patients underwent standardized cardiac evaluation including a detailed cardiovascular history and physical examination, electrocardiogram and transthoracic echocardiogram. Five patients were excluded because of poor transthoracic echocardiographic image quality, and three patients were excluded because of PFO closure prior to LT, yielding a study population of 350 patients. Medical records were reviewed to determine demographics, echocardiographic findings and outcome following LT. Major adverse cardiovascular events, myocardial infarction, CVA and death were collected. RESULTS: Mean age was 53.4 ±â€¯10.2 years; 61% male and 5% of patients had a prior history of CVA. Alcohol and hepatitis C were the most common etiologies for liver disease. Forty-six patients (13.1%) were diagnosed with PFO prior to LT. In-hospital CVA occurred in 6 patients (1.7%). The prevalence of a CVA was not significantly higher in patients with PFO compared to patients without PFO, 2.2% vs 1.6%, p = 0.57. In-hospital mortality was similar in patients with PFO compared to patients without PFO, 4.4% and 5.3%, p = 1.0. CONCLUSIONS: The presence of a PFO in patients undergoing LT is not associated with postoperative CVA. Prophylactic closure of PFOs, in the absence of other indications, does not appear to be warranted in patients undergoing LT.

Changes in Brown Adipose Tissue and Muscle Development during Infancy.

OBJECTIVE: To examine the relationship between brown adipose tissue (BAT) and muscle development, two tissues that derive from a common cell lineage, during the first 6 months of postnatal life. STUDY DESIGN: Thirty healthy term infants (15 males and females) underwent whole-body magnetic resonance imaging examinations. Measurements of BAT in the supraclavicular area as well as measures of trunk musculature and subcutaneous adiposity were obtained at birth and at 6 months of age. RESULTS: Paraspinous musculature and subcutaneous white adipose tissue (WAT) increased, and the proportion of BAT in the supraclavicular area decreased during infancy. Although measures of BAT did not correlate with paraspinous musculature through the first 6 months of life (r = -0.35; P = .09), BAT was a significant predictor of paraspinous musculature after adjusting for weight, body length, and WAT (P = .002); infants with the smallest decreases in BAT had the greatest gains in musculature. In contrast, changes in BAT did not predict increases in subcutaneous WAT (P = .25) during infancy, which were primarily determined by body weight. CONCLUSIONS: Changes in BAT are associated with muscle development but not WAT accumulation in healthy infants. Studies are needed to determine the mechanism(s) by which BAT could facilitate muscle growth, and the degree to which decreased muscle mass, such as in preterm and low birth weight infants, is related to a deficiency of BAT.

Evaluation of Sensory and Motor Skills in Neurosurgery Applicants Using a Virtual Reality Neurosurgical Simulator: The Sensory-Motor Quotient.

OBJECTIVE: Manual skill is an important attribute for any surgeon. Current methods to evaluate sensory-motor skills in neurosurgical residency applicants are limited. We aim to develop an objective multifaceted measure of sensory-motor skills using a virtual reality surgical simulator. DESIGN: A set of 3 tests of sensory-motor function was performed using a 3-dimensional surgical simulator with head and arm tracking, collocalization, and haptic feedback. (1) Trajectory planning: virtual reality drilling of a pedicle. Entry point, target point, and trajectory were scored-evaluating spatial memory and orientation. (2) Motor planning: sequence, timing, and precision: hemostasis in a postresection cavity in the brain. (3) Haptic perception: touching virtual spheres to determine which is softest of the group, with progressive difficulty. Results were analyzed individually and for a combined score of all the tasks. SETTING: The University of Chicago Hospital's tertiary care academic center. PARTICIPANTS: A total of 95 consecutive applicants interviewed at a neurosurgery residency program over 2 years were offered anonymous participation in the study; in 2 cohorts, 36 participants in year 1 and 27 participants in year 2 (validation cohort) agreed and completed all the tasks. We also tested 10 first-year medical students and 4 first- and second-year neurosurgery residents. RESULTS: A cumulative score was generated from the 3 tests. The mean score was 14.47 (standard deviation = 4.37), median score was 13.42, best score was 8.41, and worst score was 30.26. Separate analysis of applicants from each of 2 years yielded nearly identical results. Residents tended to cluster on the better performance side, and first-year students were not different from applicants. CONCLUSIONS: (1) Our cumulative score measures sensory-motor skills in an objective and reproducible way. (2) Better performance by residents hints at validity for neurosurgery. (3) We were able to demonstrate good psychometric qualities and generate a proposed sensory-motor quotient distribution in our tested population.

Sexual Dimorphism in Newborn Vertebrae and Its Potential Implications.

OBJECTIVE: To examine whether the sex-related differences in vertebral cross-sectional area (CSA) found in children and at the timing of peak bone mass-a major determinant of osteoporosis and future fracture risk-are also present at birth. STUDY DESIGN: Vertebral CSA, vertebral height, and intervertebral disc height were measured using magnetic resonance imaging in 70 healthy full-term newborns (35 males and 35 females). The length and CSA of the humerus, musculature, and adiposity were measured as well. RESULTS: Weight, body length, and head and waist circumferences did not differ significantly between males and females (P ≥ .06 for all). Compared with newborn boys, girls had significantly smaller mean vertebral cross-sectional dimensions (1.47 ± 0.11 vs 1.31 ± 0.12; P < .0001). Multiple linear regression analysis identified sex as a predictor of vertebral CSA independent of gestational age, birth weight, and body length. In contrast, the sexes were monomorphic with regard to vertebral height, intervertebral disc height, and spinal length (P ≥ .11 for all). There were also no sex differences in the length or cross-sectional dimensions of the humerus or in measures of musculature and adiposity (P ≥ .10 for all). CONCLUSION: Factors related to sex influence fetal development of the axial skeleton. The smaller vertebral CSA in females is associated with greater flexibility of the spine, which could represent the human adaptation to fetal load. Unfortunately, it also imparts a mechanical disadvantage that increases stress within the vertebrae for all physical activities and increases the susceptibility to fragility fractures later in life.