Steven G. Lloyd

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction often coexist with overlapping clinical features, they are usually studied separately. The SPIROMICS HF (Subpopulations and Intermediate Outcome Measures in COPD and Heart Failure Study) is testing hypotheses that new computed tomography emphysema subtypes are associated with specific cardiovascular phenotypes (eg, cor pulmonale , cor pulmonale parvus ), common airway branch variants are associated with right heart dysfunction, and symptomatic tobacco-exposed persons with preserved spirometry have signs of increased left ventricular afterload. METHODS: SPIROMICS is a multicenter observational study of COPD with extensive pulmonary phenotyping of participants with ≥20 pack-years smoking and nonsmoking controls. COPD and COPD severity were defined by standard spirometric criteria and symptomatic tobacco-exposed persons with preserved spirometry by ≥20 pack-years, normal spirometry, and COPD Assessment Test score >10. SPIROMICS HF selected all participants in SPIROMICS visit 5 at major sites. Its comprehensive speckle-tracking echocardiography, which included physiological perturbations of leg raise and low-intensity exercise, was harmonized prospectively with the Multi-Ethnic Study of Atherosclerosis Early Heart Failure and HeartSHARE (Combining Omics, Deep Phenotyping, and Electronic Health Records for Heart Failure Subtypes and Treatment Targets) studies. The cardiopulmonary magnetic resonance imaging protocol with gadolinium administration included myocardial fibrosis sequences, pulmonary angiography, time-resolved 3-dimensional cine magnetic resonance imaging (4-dimensional flow) of venous return, and metronome-paced tachypnea to induce dynamic hyperinflation. Coronary artery calcium was assessed on computed tomography scans. The Kansas City Cardiomyopathy Questionnaire was administered. RESULTS: Of the final sample of 753 participants, 57% had COPD (15% mild, 27% moderate, and 15% severe), 18% had symptomatic tobacco-exposed persons with preserved spirometry, 16% were smoking controls, and 8% were nonsmoking controls. Reproducibility of the main measures from speckle-tracking echocardiography (intraclass correlation coefficient, 0.83–0.99), exercise echocardiography (intraclass correlation coefficient, 0.71–0.99) and magnetic resonance imaging (intraclass correlation coefficient, 0.57–0.99) were good-to-excellent, including in severe COPD. CONCLUSIONS: SPIROMICS HF aims to characterize and understand cardiopulmonary interactions in COPD and COPD-related phenotypes to inform targeted treatments for combined cardiopulmonary failure.

Purpose Knowledge of the timing of cardiac valve opening and closing is important in cardiac physiology. The relationship between valve motion and electrocardiogram (ECG) is often assumed, however is not clearly defined. Here we investigate the accuracy of cardiac valve timing estimated using only the ECG, compared to Doppler echocardiography (DE) flow imaging as the gold standard. Methods DE was obtained in 37 patients with simultaneous ECG recording. ECG was digitally processed and identifiable features (QRS, T, P waves) were examined as potential reference points to determine opening and closure of aortic and mitral valves, as compared to DE outflow and inflow measurement. Timing offset of the cardiac valves opening and closure between ECG features and DE was measured from derivation set (n = 19). The obtained mean offset in combination with the ECG features model was then evaluated on a validation set (n = 18). Using the same approach, additional measurement was also done for the right sided valves. Results From the derivation set, we found a fixed offset of 22 ± 9 ms, 2 ± 13 ms, 90 ± 26 ms, and − 2 ± − 27 ms when comparing S to aortic valve opening, T_end to aortic valve closure, T_end to mitral valve opening, and R to mitral valve closure respectively. Application of this model to the validation set showed good estimation of aortic and mitral valve opening and closure timing value, with low model absolute error (median of the mean absolute error of the four events = 19 ms compared to the gold standard DE measurement). For the right-sided (tricuspid and pulmonic) valves in our patient set, there was considerably higher median of the mean absolute error of 42 ms for the model. Conclusion ECG features can be used to estimate aortic and mitral valve timings with good accuracy as compared to DE, allowing useful hemodynamic information to be derived from this easily available test.

Background: Virtual interviewing for cardiology fellowship was instituted in the 2021 fellowship application cycle because of the COVID‐19 pandemic and restricted travel. The impact on geographic patterns of fellow‐training program matching is unknown. This study sought to determine if there was a difference in geographic placement of matched fellows for cardiology fellowship match after initiation of virtual interviews compared with in‐person interviewing. Methods and Results: All US‐based accredited cardiovascular disease fellowship programs that participated in the 2019 to 2021 fellowship match cycles and had publicly available data with fellowship and residency training locations and training year were included. Each fellow was categorized based on whether their fellowship and residency programs were in the same institution, same state, same US census region, or different census region. Categories were mutually exclusive. Of 236 eligible programs, 118 (50%) programs were identified, composed of 1787 matched fellows. Compared with the previrtual cohort (n=1178 matched fellows), there was no difference in the geographic placement during the 2021 virtual cycle (n=609 matched fellows) ( P =0.19), including the proportion matched at the same program (30.6% versus 31.5%), same state but different program (13% versus 13.8%), same region but different state (24.2% versus 19.7%), or different region (35% versus 33.1%). There was also no difference when stratified by program size or geographic region. Conclusions: The use of virtual interviewing in the 2021 cardiology fellowship application cycle showed no significant difference in the geographic placement of matched fellows compared with in‐person interviewing. Further study is needed to evaluate the impact of virtual interviewing and optimize its use in fellowship recruitment.

Background: We previously reported increased plasma XO (xanthine oxidase) activity in patients with resistant hypertension. Increased XO can cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Here, we report racial differences in XO activity and mtDNA DAMPs in Black and White adults with resistant hypertension. Methods: This retrospective study includes 91 resistant hypertension patients (44% Black, 47% female) with blood pressure >140/90 mm Hg on ≥4 medications and 37 normotensive controls (30% Black, 54% female) with plasma XO activity, mtDNA DAMPs, and magnetic resonance imaging of left ventricular morphology and function. Results: Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; P =0.001), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion (mg/24 hour per kg) was positively related to left ventricular end-diastolic volume ( r =0.527, P =0.001) and left ventricular mass ( r =0.394, P =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( P P <0.001). Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrates mitochondria cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation. Conclusions: These data warrant a large study to examine the role of XO and mitochondrial mtDNA DAMPs in cardiac remodeling and heart failure in Black adults with resistant hypertension.

Objective. We developed a method using cardiovascular magnetic resonance imaging to model the untwisting of the left ventricle (LV) as a damped torsional harmonic oscillator to estimate shear modulus (intrinsic myocardial stiffness) and frictional damping, then applied this method to evaluate the torsional stiffness of patients with resistant hypertension (RHTN) compared to a control group. Approach. The angular displacement of the LV during diastole was measured. Myocardial shear modulus and damping constant were determined by solving a system of equations modeling the diastolic untwisting as a damped, unforced harmonic oscillator, in 100 subjects with RHTN and 36 control subjects. Main Results. Though overall torsional stiffness was increased in RHTN (41.7 (27.1–60.7) versus 29.6 (17.3–35.7) kdyn*cm; p = 0.001), myocardial shear modulus was not different between RHTN and control subjects (0.34 (0.23–0.50) versus 0.33 (0.22–0.46) kPa; p = 0.758). RHTN demonstrated an increase in overall diastolic frictional damping (6.13 ± 3.77 versus 3.35 ± 1.70 kdyn*cm*s; p < 0.001), but no difference in damping when corrected for the overlap factor (74.3 ± 25.9 versus 68.0 ± 24.0 dyn*s/cm ³ ; p = 0.201). There was an increase in the polar moment (geometric component of stiffness; 11.47 ± 6.95 versus 7.58 ± 3.28 cm ⁴ ; p Significance. We have developed a phenomenological method, estimating the intrinsic stiffness and relaxation properties of the LV based on restorative diastolic untwisting. This model finds increased overall stiffness in RHTN and points to hypertrophy, rather than tissue- level changes, as the major factor leading to increased stiffness.

Background: Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results: Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase‐contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P P P <0.001, respectively) following 6 months of spironolactone. Conclusions: Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Dr. Al-Mubarak and colleagues evaluate the accuracy of CCAs compared to CMR imaging in determining the site of origin and proximal course of ACAs.

Background: In 2016, the American Society of Echocardiography (ASE) released guidelines for identifying left ventricular (LV) diastolic dysfunction (DD), but its ability to detect early hemodynamic abnormalities is not well established, especially in the setting of subclinical coronary artery disease (CAD). We hypothesize that the accuracy of ASE categorization of early LVDD is affected by knowledge of whether CAD history is present.Methods: We studied 34 patients (age 62 ± 7 years) with NYHA class I to II symptoms and with transthoracic echocardiography without findings suggesting myocardial disease (all with preserved LV ejection fraction), who underwent cardiac catheterization with high‐fidelity LV pressure measurement. Echocardiographic images were evaluated for LVDD using ASE algorithm without and with knowledge of CAD history and angiography findings. CAD was considered as having DD for the algorithm.Results: CAD was identified in 22 patients at catheterization (65%). Using ASE guidelines without including history of CAD or angiographic results, 29 patients were DD−, 3 were DD+ (all grade II), and 2 were indeterminate. Inclusion of CAD history recategorized 59% (n = 20) patients to DD+ (all grade I) from DD− (P < .0001). Nineteen of the recategorized patients (95%) had increased isovolumetric relaxation time (IVRT). The addition of echocardiographic IVRT improved discrimination between DD− and DD+, when the presence of CAD is unknown.Conclusions: 2016‐ASE algorithm reasonably accurately identifies early LVDD at rest as reflected by LV catheterization when CAD is disclosed, but without knowledge of the presence of CAD, it underdiagnoses DD+ grade I. The addition of IVRT may improve early LVDD diagnostics.