Cardiovascular Burden of the V142I Transthyretin Variant.

Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. Exposure: V142I carrier status (n = 754, 3.2%). Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Transthyretin amyloid cardiomyopathy among patients hospitalized for heart failure and performance of an adapted wild-type ATTR-CM machine learning model: Findings from GWTG-HF.

BACKGROUND: An 11-factor random forest model has been developed among ambulatory heart failure (HF) patients for identifying potential wild-type amyloidogenic TTR cardiomyopathy (wtATTR-CM). The model has not been evaluated in a large sample of patients hospitalized for HF. METHODS: This study included Medicare beneficiaries aged ≥65 years hospitalized for HF in the Get With The Guidelines-HF® Registry from 2008-2019. Patients with and without a diagnosis of ATTR-CM were compared, as defined by inpatient and outpatient claims data within 6 months pre- or post-index hospitalization. Within a cohort matched 1:1 by age and sex, univariable logistic regression was used to evaluate relationships between ATTR-CM and each of the 11 factors of the established model. Discrimination and calibration of the 11-factor model were assessed. RESULTS: Among 205,545 patients (median age 81 years) hospitalized for HF across 608 hospitals, 627 patients (0.31%) had a diagnosis code for ATTR-CM. Univariable analysis within the 1:1 matched cohort of each of the 11-factors in the ATTR-CM model found pericardial effusion, carpal tunnel syndrome, lumbar spinal stenosis, and elevated serum enzymes (e.g., troponin elevation) to be strongly associated with ATTR-CM. The 11-factor model showed modest discrimination (c-statistic 0.65) and good calibration within the matched cohort. CONCLUSIONS: Among US patients hospitalized for HF, the number of patients with ATTR-CM defined by diagnosis codes on an inpatient/outpatient claim within 6 months of admission was low. Most factors within the prior 11-factor model were associated with greater odds of ATTR-CM diagnosis. In this population, the ATTR-CM model demonstrated modest discrimination.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

BACKGROUND: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. METHODS: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. RESULTS: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). CONCLUSIONS: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.

Effects of Exercise Therapy Dosing Schedule on Impaired Cardiorespiratory Fitness in Patients With Primary Breast Cancer: A Randomized Controlled Trial.

BACKGROUND: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40-50 minutes per session), and volume (120-160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer. METHODS: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO2peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak (mL O2·kg-1·min-1) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety. RESULTS: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO2peak increased 0.6±1.7 mL O2·kg-1·min-1 (P=0.05) and 0.8±1.8 mL O2·kg-1·min-1 (P=0.07) in LET and NLET, respectively, compared with attention control. Change in VO2peak ranged from -2.7 to 4.1 mL O2·kg-1·min-1 and from -3.6 to 5.1 mL O2·kg-1·min-1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO2peak responders (ie, Δ ≥1.32 mL O2·kg-1·min-1). NLET improved all patient-reported outcomes compared with attention control. CONCLUSIONS: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01186367.

Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial.

BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. METHODS: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. RESULTS: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. CONCLUSIONS: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Outcomes following cardioversion for patients with cardiac amyloidosis and atrial fibrillation or atrial flutter.

Atrial arrhythmias commonly occur in patients with cardiac amyloidosis (CA), but there is limited data on safety or efficacy of cardioversion (DCCV) for management of these rhythms in CA. We identified 25 patients with CA (20 with transthyretin (TTR) and 5 with light-chain (AL) amyloidosis) at Duke University who underwent DCCV for atrial arrhythmias and documented procedural success, complications, and long-term morbidity and mortality. While DCCV successfully restored sinus rhythm in 96% of patients, 36% of patients experienced immediate procedural complications (primarily bradycardia and hypotension), 80% had recurrence of atrial arrhythmias at 1 year, and 52% died at 3 years, highlighting short-term safety concerns, long-term inefficacy, and poor prognosis associated with symptomatic atrial arrhythmias requiring DCCV in CA.

Catheter ablation of atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). METHODS: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review. RESULTS: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years. CONCLUSIONS: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced-stage CA.

On the use of remote sensing to map the proliferation of aquaculture ponds and to investigate their effect on local climate, perspectives from the Claise watershed, France.

Ponds, as landscape features, are known to regulate climate. Since ponds proliferate or recede due to natural or anthropogenic factors, a variation of pond numbers implies a variation of their climatic effect. Accordingly, this study investigates the impact of ponds on the local climate of the French Claise watershed. The latter was chosen because it contains a pond dense zone and a pondless zone. This repartition makes the Claise an adequate context to reveal the climatic impact of ponds even in the same landscape. To study the pond-climate effect, the parallel evolution of pond numbers variation and subsequent climatic impact must be tracked. Therefore, the remote sensing-derived Normalized Difference Water Index (NDWI) was extracted from LANDSAT images with different acquisition dates to track changes in pond numbers with time. When compared with a pond map established from aerial photography interpretation, the LANDSAT NDWI map revealed an accuracy of 85.74% for pond count and 75% for pond spatial allocation. This validation showed that NDWI is suitable for mapping the proliferation of ponds through time. In order to study the parallel evolution of the climatic effect, the land surface temperature (LST) index was extracted for each LANDSAT map. LST maps revealed that as a result of pond number variation, surface temperatures varied accordingly. A comparison of air temperatures between the ponded zone and pondless zones also revealed that pond zones had lower air temperatures than their direct surroundings. Accordingly, ponds were shown to buffer local microclimates even within the same landscape.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient.

BACKGROUND: Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. METHODS: We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. RESULTS: Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was -14.6% (-13.7 to -17.3%); LV GLS was abnormal (ie, >-16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; -11.0 to -13.4%) and 3 months (median -11.4%; -10.3 to -13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. CONCLUSIONS: GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Cardiac Dysfunction and Heart Failure in Hematopoietic Cell Transplantation Survivors: Emerging Paradigms in Pathophysiology, Screening, and Prevention.

Hematopoietic cell transplantation (HCT) has been used for curative intent in patients with hematologic and nonhematologic malignancies, resulting in an increasing number of HCT survivors. These survivors are at risk for serious and life-threatening complications, including cardiovascular disease (CVD). This article provides an overview of CVD in HCT survivors, describing the pathophysiology of disease, with a special emphasis on therapeutic exposures and comorbidities unique to this population. This article also discusses novel screening and prevention strategies that have shown promise in non-HCT cancer populations, emphasizing opportunities for collaboration between cardiologists and hematologists to improve the cardiovascular health of HCT survivors.

Ventricular-Arterial Coupling in Breast Cancer Patients After Treatment With Anthracycline-Containing Adjuvant Chemotherapy.

BACKGROUND: Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C. METHODS: Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured. RESULTS: Thirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05). CONCLUSION: In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls. IMPLICATIONS FOR PRACTICE: Anthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.

Pre-exercise participation cardiovascular screening in a heterogeneous cohort of adult cancer patients.

BACKGROUND: The purpose of this study was to investigate the extent of pre-exercise participation ("preparticipation") health screening in a heterogeneous cohort of adult cancer patients. METHODS: Patients (n = 413) with histologically confirmed solid or hematologic malignancy were categorized into preparticipation health screening risk stratification based on American College Sports Medicine (ACSM) recommendations. Risk of an exercise-related event was evaluated during a symptom-limited cardiopulmonary exercise test (CPET) with 12-lead electrocardiography (ECG). RESULTS: Participant risk was categorized as low risk (n = 59, 14%), moderate risk (n = 217, 53%), and high risk (n = 137, 33%). Mean peak oxygen consumption was 21.7 ± 6.7 mL/kg(-1) per minute(-1) or 19.5 ± 21.7% below age- and sex-predicted sedentary values. No major serious adverse events or fatal events were observed during CPET procedures. A total of 31 positive ECG tests were observed, for an event rate of 8%. ACSM risk stratification did not predict the risk of a positive test. Age, statin use, antiplatelet therapy use, cardiovascular disease, prior treatment with anthracycline or radiation therapy, and being sedentary were predictors of a positive test (all p < .10). CONCLUSION: The patient risk-stratification profile strongly suggests that the use of formalized preparticipation health screening is required in all oncology scenarios; however, risk of an exercise-induced event is low, suggesting that the use of exercise testing is not required for pre-exercise clearance in the majority of patients.

Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy.

Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to -17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (-16.1 ± 0.9 vs. -20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min(-1) m(-2) mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0.001). Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients.

Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy.

AIMS: Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. METHODS AND RESULTS: In 131 patients referred for cardiac resynchronization therapy (CRT) from two international centres, mechanical dyssynchrony was assessed from TDI velocity curves using time-to-peak opposing wall delay (OWD) ≥80 ms, Yu index ≥32 ms, and the maximal activation delay (AD-max) >35 ms. AD-max was calculated by XCA of the TDI-derived myocardial acceleration curves. Outcome was a composite of all-cause mortality, cardiac transplantation, or implantation of a ventricular assist device (left ventricular assist device) and modelled using the Cox proportional hazards regression. Follow-up was truncated at 1460 days. Dyssynchrony by AD-max was independently associated with improved survival when adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed significantly better than Yu index, OWD, and the presence of left bundle branch block (P < 0.05, all, for difference between parameters). In subgroup analysis, patients without dyssynchrony and QRS between 120 and 150 ms showed a particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P < 0.01, compared with the group with dyssynchrony and QRS between 120 and 150 ms]. CONCLUSION: Mechanical dyssynchrony assessed by AD-max was associated with long-term survival after CRT and was significantly better associated compared with other TDI-derived indices. Patients without dyssynchrony and QRS between 120 and 150 ms had a particularly poor prognosis. These results indicate a valuable role for XCA in selection of CRT candidates.

Pressures do not equal volumes: implications for heart failure management in patients with CardioMEMS.

Pulmonary arterial pressures are often used as surrogates for intravascular blood volume. However, the relationship between pressure and volume remains controversial. To contextualize and provide concrete examples and impact on clinical management, we report two cases of heart failure (one in heart failure with reduced ejection fraction and one in heart failure with preserved ejection fraction) where pressure-based measurements did not accurately represent the intravascular status and affected clinical management.

Evaluation of Myocardial Stiffness in Cardiac Amyloidosis Using Acoustic Radiation Force Impulse and Natural Shear Wave Imaging.

OBJECTIVE: Increased myocardial stiffness (MS) is an important hallmark of cardiac amyloidosis (CA) caused by myocardial amyloid deposition. Standard echocardiography metrics assess MS indirectly via downstream effects of cardiac stiffening. The ultrasound elastography methods acoustic radiation force impulse (ARFI) and natural shear wave (NSW) imaging assess MS more directly. METHODS: This study compared MS in 12 healthy volunteers and 13 patients with confirmed CA using ARFI and NSW imaging. Parasternal long-axis acquisitions of the interventricular septum were obtained using a modified Acuson Sequoia scanner and a 5V1 transducer. ARFI-induced displacements were measured through the cardiac cycle, and ratios of diastolic-over-systolic displacement were calculated. NSW speeds from aortic valve closure were extracted from echocardiography-tracked displacement data. RESULTS: ARFI stiffness ratios were significantly lower in CA patients than controls (mean ± standard deviation: 1.47 ± 0.27 vs. 2.10 ± 0.47, p < 0.001), and NSW speeds were significantly higher in CA patients than controls (5.58 ± 1.10 m/s vs. 3.79 ± 1.10 m/s, p < 0.001). A linear combination of the two metrics exhibited greater diagnostic potential than either metric alone (area under the curve = 0.97 vs. 0.89 and 0.88). CONCLUSION: MS was measured to be significantly higher in CA patients using both ARFI and NSW imaging. Together, these methods have potential utility to aid in clinical diagnosis of diastolic dysfunction and infiltrative cardiomyopathies.

A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND).

BACKGROUND: Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSI) are associated with deleterious physical effects, which exercise may mitigate; however, exercise has never been studied in patients initiating treatment with ADT and an ARSI. Our objective was to determine whether supervised exercise prior to and during initial therapy could mitigate adverse effects of ADT plus enzalutamide. METHODS: We conducted a single center trial in patients with recurrent prostate cancer treated with ADT and enzalutamide. We randomized 26 patients to 16 weeks of supervised exercise (aerobic and resistance), starting 4 weeks before initiation of ADT and enzalutamide, or usual care. The primary endpoint was change in peak oxygen uptake (VO2peak) as a measure of cardiorespiratory fitness (CRF). Secondary endpoints were functional capacity, maximal strength, body composition, patient-reported outcomes, safety, and feasibility. Analysis of covariance was used to compare outcomes for groups at Week 17 adjusted for baseline values. RESULTS: The usual care group (N = 13) showed declines from baseline to week 17 in both absolute CRF (-0.31 L/min, -10.9%; p < 0.01) and relative CRF (-3.2 mL/kg/min, -8.9%; p = 0.04); worse fatigue (p = 0.01); and worse quality of life (p = 0.01). At week 17, the exercise group (N = 13) demonstrated improved absolute CRF (between-group change +0.20 L/min, p = 0.05), leg strength (+48.6 kg, p < 0.01) and functional capacity (+21.0 m, p = 0.01) at week 17. CONCLUSIONS: This is the first randomized controlled trial demonstrating a clinically significant decline in CRF in patients initiating ADT and enzalutamide. We show the effectiveness of short-term supervised exercise to mitigate declines in absolute CRF, and improve maximal leg strength and functional capacity. GOV IDENTIFIER: NCT02256111.

Cardiometabolic Comorbidities in Cancer Survivors: JACC: CardioOncology State-of-the-Art Review.

There are nearly 17 million cancer survivors in the United States, including those who are currently receiving cancer therapy with curative intent and expected to be long-term survivors, as well as those with chronic cancers such as metastatic disease or chronic lymphocytic leukemia, who will receive cancer therapy for many years. Current clinical practice guidelines focus on lifestyle interventions, such as exercise and healthy eating habits, but generally do not address management strategies for clinicians or strategies to increase adherence to medications. We discuss 3 cardiometabolic comorbidities among cancer survivors and present the prevalence of comorbidities prior to a cancer diagnosis, treatment of comorbidities during cancer therapy, and management considerations of comorbidities in long-term cancer survivors or those on chronic cancer therapy. Approaches to support medication adherence and potential methods to enhance a team approach to optimize care of the individual with cancer across the continuum of disease are discussed.