Faculty Bibliography

BACKGROUND:While aortic valve sclerosis (AVS) is well-described as preceding aortic stenosis (AS), the association of AS with antecedent mitral aortic annular calcification and aortic annulus increased reflectivity (MAC and AAIR, respectively) has not been characterized. In a population-based prospective study, we evaluated whether MAC, AAIR, and AVS are associated with the risk of incident AS. METHODS:Among participants of the Cardiovascular Health Study (CHS) free of AS at the 1994-1995 visit, the presence of MAC, AAIR, AVS, and the combination of all three were evaluated in 3041 participants. Cox proportional hazards regression was used to assess the association between the presence of calcification and the incidence of moderate/severe AS in three nested models adjusting for factors associated with atherosclerosis and inflammation both relevant to the pathogenesis of AS. RESULTS:Over a median follow-up of 11.5 years (IQR 6.7 to 17.0), 110 cases of incident moderate/severe AS were ascertained. Strong positive associations with incident moderate/severe AS were found for all calcification sites after adjustment for the main model covariates: AAIR (HR=2.90, 95% CI=[1.95, 4.32], p<0.0005), AVS (HR=2.20, 95% CI=[1.44, 3.37], p<0.0005), MAC (HR=1.67, 95% CI=[1.14, 2.45], p=0.008), and the combination of MAC, AAIR, and AVS (HR=2.50, 95% CI=[1.65, 3.78], p<0.0005). In a secondary analysis, the risk of AS increased with the number of sites at which calcification was present. CONCLUSIONS:In a large cohort of community-dwelling elderly individuals, there were strong associations between each of AAIR, AVS, MAC, and the combination of MAC, AAIR, and AVS with incident moderate/severe AS. The novel finding that AAIR had a particularly strong association with incident AS, even after adjusting for other calcification sites, suggests its value in identifying individuals at risk for AS, and potential inclusion in the routine assessment by transthoracic echocardiography.

BACKGROUND:Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE:We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS:We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS:Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION/CONCLUSIONS:Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy. Implantable Cardioverter Defibrillator (ICD) is important for prevention of sudden cardiac death (SCD) in patients at high risk. In recent years the subcutaneous ICD (S-ICD) has emerged as a viable alternative to the transvenous ICD (TV-ICD). The S-ICD does not require intravascular access, but cannot provide antitachycardia pacing therapy (ATP). OBJECTIVE:To assess the real world incidence of ICD therapy in patients with HCM implanted with TV-ICD versus S-ICD. METHODS:We compared the incidence of ATP and shock therapies between all HCM patients with S-ICD and TV-ICD enrolled in the Boston Scientific ALTITUDE database. Cumulative Kaplan Meier incidence was used to compare therapy free survival and Cox proportional hazard ratios were calculated. We performed an unmatched as well as propensity match analysis. RESULTS:We included 2047 patients with TV-ICD and 626 patients with S-ICD followed for an average of 1650.5±1038.5 and 933.4±550.6 days, respectively. Patients with HCM and TV-ICD had significantly higher rate of device therapy as compared to those with S-ICD (32.7 vs. 14.5 therapies /100 patient year; p<0.001), driven by a high incidence of ATP therapy in the TV-ICD group which accounted for more than 67% of therapies delivered. Shock incidence was similar between groups, both in the general and in the matched cohorts. CONCLUSIONS:Patients with HCM and S-ICD had significantly lower therapy rate than patients with TV-ICD without difference in shock therapy, suggesting potentially unnecessary ATP therapy. Empiric ATP programing in patients with HCM may be unbeneficial.

OBJECTIVES/OBJECTIVE:Speckle-tracking echocardiography enables detection of abnormalities in cardiac mechanics with higher sensitivity than conventional measures of left ventricular (LV) dysfunction and may provide insight into the pathogenesis of coronary heart disease (CHD). We investigated the relationship of LV longitudinal strain, LV early diastolic strain rate (SR) and left atrial (LA) reservoir strain with long-term CHD incidence in community-dwelling older adults. METHODS:The association of all three strain measures with incidence of non-fatal and fatal CHD (primary outcome of revascularisation, non-fatal and fatal myocardial infarction) was examined in the population-based Cardiovascular Health Study using multivariable Cox proportional hazards models. Follow-up was truncated at 10 years. RESULTS:We included 3313 participants (mean (SD) age 72.6 (5.5) years). During a median follow-up of 10.0 (25th-75th percentile 7.7-10.0) years, 439 CHD events occurred. LV longitudinal strain (HR=1.25 per SD decrement, 95% CI 1.09 to 1.43) and LV early diastolic SR (HR=1.31 per SD decrement, 95% CI 1.14 to 1.50) were associated with a significantly greater risk of incident CHD after adjustment for potential confounders. By contrast, LA reservoir strain was not associated with incident CHD (HR=1.06 per SD decrement, 95% CI 0.94 to 1.19). Additional adjustment for biochemical and echocardiographic measures of myocardial stress, dysfunction and remodelling did not meaningfully alter these associations. CONCLUSION/CONCLUSIONS:We found an association between echocardiographic measures of subclinically altered LV mechanics and incident CHD. These findings inform the underlying biology of subclinical LV dysfunction and CHD. Early detection of asymptomatic myocardial dysfunction may offer an opportunity for prevention and early intervention.

BACKGROUND:Changes in mitral valve anatomy contribute to left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM). Mitral annular calcification (MAC) is common among patients with HCM but its implications are currently unknown. METHODS:We tested the hypothesis that echocardiographic MAC would be associated with anterior displacement of the mitral valve and LVOTO in a cohort of 304 patients with HCM aged ≥ 60 years (mean [SD] age 71.6 [7.7] years, 52% women). RESULTS:MAC was present in 141 (46%) patients. The mean (SD) MAC offset distance was 9.8 (4.8) mm. A higher proportion of those with MAC compared to those without MAC had SAM (84.2 vs. 63.8%, p < 0.001) and LVOTO (80.9 vs. 57.9%, p < 0.001). In patients with MAC, the septal-mitral valve distance was shorter compared to those without (19.4 [4.0] vs 21.5 [4.9] mm, p < 0.001). The mitral valve position ratio was greater in those with MAC compared to those without (1.00 [0.79, 1.22] vs. 0.86 [0.67, 1.05], p < 0.001) denoting greater anterior displacement, especially in those with MAC and LVOTO. After multivariable adjustment, MAC offset distance was associated with LVOTO (OR 1.16 [95% CI 1.07, 1.28] per mm, p = 0.001). Over a median follow-up of 2.7 years, 42 (29.8%) patients with MAC underwent surgery to relieve LVOTO, with no deaths. CONCLUSION/CONCLUSIONS:This study adds MAC to the known geometrical alterations of the mitral valve that predispose to LVOTO and suggests that surgical relief of LVOTO in the presence of MAC is safe when performed by an experienced surgeon.

BACKGROUND:F-NaF PET/CT are based on evaluations of end-diastolic or cardiac motion-corrected (ECG-MC) images, which are affected by both patient and respiratory motion. We aimed to test the impact of employing a triple motion correction technique (3 × MC), including cardiorespiratory and gross patient motion, on quantitative and qualitative measurements. MATERIALS AND METHODS/METHODS:) values after correcting for blood pool activity. RESULTS:: Standard = 0.20, ECG-MC = 0.28, and 3 × MC = 0.46). CONCLUSION/CONCLUSIONS:F-NaF.

OBJECTIVES/OBJECTIVE:Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. METHODS:This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. RESULTS:). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). CONCLUSIONS:Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.

Background Cardiogenic shock from most causes has unfavorable prognosis. Hypertrophic cardiomyopathy (HCM) can uncommonly present with apical ballooning and shock in association with sudden development of severe and unrelenting left ventricular (LV) outflow obstruction. Typical HCM phenotypic features of mild septal thickening, outflow gradients, and distinctive mitral abnormalities differentiate these patients from others with Takotsubo syndrome, who have normal mitral valves and no outflow obstruction. Methods and Results We analyzed 8 patients from our 4 HCM centers with obstructive HCM and abrupt presentation of cardiogenic shock with LV ballooning, and 6 cases reported in literature. Of 14 patients, 10 (71%) were women, aged 66±9 years, presenting with acute symptoms: LV ballooning; depressed ejection fraction (25±5%); refractory systemic hypotension; marked LV outflow tract obstruction (peak gradient, 94±28 mm Hg); and elevated troponin, but absence of atherosclerotic coronary disease. Shock was managed with intravenous administration of phenylephrine (n=6), norepinephrine (n=6), β-blocker (n=7), and vasopressin (n=1). Mechanical circulatory support was required in 8, including intra-aortic balloon pump (n=4), venoarterial extracorporeal membrane oxygenation (n=3), and Impella and Tandem Heart in 1 each. In refractory shock, urgent relief of obstruction by myectomy was performed in 5, and alcohol ablation in 1. All patients survived their critical illness, with full recovery of systolic function. Conclusions When cardiogenic shock and LV ballooning occur in obstructive HCM, they are marked by distinctive anatomic and physiologic features. Relief of obstruction with targeted pharmacotherapy, mechanical circulatory support, and myectomy, when necessary for refractory shock, may lead to survival and normalization of systolic function.