Agreement among high-sensitivity cardiac troponin assays and non-invasive testing, clinical outcomes, and quality-of-care outcomes based on the 2020 European Society of Cardiology Guidelines.

AIMS: Quality-of-care and safety of patients with suspected acute coronary syndrome (ACS) would benefit if management was independent of which high-sensitivity cardiac troponin (hs-cTn) assay was used for risk stratification. We aimed to determine the concordance of hs-cTn assays to risk-stratify patients with suspected ACS according to the European Society of Cardiology (ESC) 2020 Guidelines. METHODS AND RESULTS: Blood samples were obtained at arrival and at 2 h from patients with suspected ACS using four hs-cTn assays. The patients were classified into rule-out/observe/rule-in strata based on the ESC 2020 Guidelines. Concordance was determined among the assays for rule-out/observe/rule-in strata. The prevalences of significant underlying disease (≥50% stenosis on coronary computed tomography or inducible myocardial ischaemia on stress testing) and adjudicated ACS, plus quality-of-care outcomes, were compared. Among 238 patients (52.7 ± 8.0 years; 40.3% female), the overall concordance across assays to classify patients into rule-out/observe/rule-in strata was 74.0% (176/238). Platforms significantly differed for rule-out (89.9 vs. 76.5 vs. 78.6 vs. 86.6%, P < 0.001) and observe strata (6.7 vs. 20.6 vs. 17.7 vs. 9.2%, P < 0.001), but not for rule-in strata (3.4 vs. 2.9 vs. 3.8 vs. 4.2%, P = 0.62). Among patients in ruled-out strata, 19.1-21.6% had significant underlying disease and 3.3-4.2% had ACS. The predicted disposition of patients and cost-of-care differed across the assays (all P < 0.001). When compared with observed strata, conventional troponin-based management and predicted quality-of-care outcomes significantly improved with hs-cTn-based strategies (direct discharge: 21.0 vs. 80.3-90.8%; cost-of-care: $3889 ± 4833 vs. $2578 ± 2896-2894 ± 4371, all P < 0.001). CONCLUSION: Among individuals with suspected ACS, patient management may differ depending on which hs-cTn assay is utilized. More data are needed regarding the implications of inter-assay differences. TRAIL REGISTRATION: NCT01084239.

Global Longitudinal Strain as Predictor of Inducible Ischemia in No Obstructive Coronary Artery Disease in the CIAO-ISCHEMIA Study.

BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA). OBJECTIVES: To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA. METHODS: Left ventricular GLS was calculated offline on resting SE images at enrollment (n = 144) and 1-year follow-up (n = 120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography. RESULTS: Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS = -21.5% positive SE vs GLS = -19.9% negative SE, P = .443) or follow-up (GLS = -23.2% positive SE vs GLS = -23.1% negative SE, P = .859). Significant change in GLS was not associated with positive SE in follow-up (P = .401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (ß = 0.41; 95% CI, 0.16, 0.67; P = .002). CONCLUSIONS: In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.

Body Mass Index and Clinical and Health Status Outcomes in Chronic Coronary Disease and Advanced Kidney Disease in the ISCHEMIA-CKD Trial.

OBJECTIVE: This study aimed to assess whether an obesity paradox (lower event rates with higher body mass index [BMI]) exists in participants with advanced chronic kidney disease (CKD) and chronic coronary disease in the International Study of Comparative Health Effectiveness of Medical and Invasive Approaches (ISCHEMIA)-CKD, and whether BMI modified the effect of initial treatment strategy. METHODS: Baseline BMI was analyzed as both a continuous and categorical variable (< 25, ≥ 25 to < 30, ≥ 30 kg/m2). Associations between BMI and the primary outcome of all-cause death or myocardial infarction (D/MI), and all-cause death, cardiovascular death, and MI individually were estimated. Associations with health status were also evaluated using the Seattle Angina Questionnaire-7, the Rose Dyspnea Scale, and the EuroQol-5D Visual Analog Scale. RESULTS: Body mass index ≥ 30 kg/m2 vs < 25 kg/m2 demonstrated increased risk for MI (hazard ratio [HR] [95% confidence interval] = 1.81 [1.12-2.92]) and for D/MI (HR 1.45 [1.06-1.96]) with a HR for MI of 1.22 (1.05-1.40) per 5 kg/m2 increase in BMI in unadjusted analysis. In multivariate analyses, a BMI ≥ 30 kg/m2 was marginally associated with D/MI (HR 1.43 [1.00-2.04]) and greater dyspnea throughout follow-up (P < .05 at all time points). Heterogeneity of treatment effect between baseline BMI was not evident for any outcome. CONCLUSIONS: In the ISCHEMIA-CKD trial, an obesity paradox was not detected. Higher BMI was associated with worse dyspnea, and a trend toward increased D/MI and MI risk. Larger studies to validate these findings are warranted.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

BACKGROUND: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). OBJECTIVES: This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death. METHODS: Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified. RESULTS: A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy. CONCLUSIONS: In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360).

The association of exercise test variables with long-term mortality in patients with chronic Chagas disease.

Background: The identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD. Methods: This retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality. Results: There were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25-75% 8.0-27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00-1.03 per mmHg) and change (HR 1.03; 95% CI 1.01-1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14-13.74), during exercise (HR 2.73; 95% CI 1.44-5.20), and recovery (HR 2.60; 95% CI 1.14-5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33-3.21). Conclusion: Our findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.

Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

BACKGROUND: Patients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m2]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5. METHODS: This was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5. RESULTS: A total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status. CONCLUSIONS: CKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.

Eliminating Disparities in Cardiovascular Disease for Black Women: JACC Review Topic of the Week.

Black women are disproportionately affected by cardiovascular disease with an excess burden of cardiovascular morbidity and mortality. In addition, the racialized structure of the United States shapes cardiovascular disease research and health care delivery for Black women. Given the indisputable evidence of the disparities in health care delivery, research, and cardiovascular outcomes, there is an urgent need to develop and implement effective and sustainable solutions to advance cardiovascular health equity for Black women while considering their ethnic diversity, regions of origin, and acculturation. Innovative and culturally tailored strategies that consider the differential impact of social determinants of health and the unique challenges that shape their health-seeking behaviors should be implemented. A patient-centered framework that involves collaboration among clinicians, health care systems, professional societies, and government agencies is required to improve cardiovascular outcomes for Black women. The time is "now" to achieve health equity for all Black women.

Cardiovascular and Renal Implications of Myocardial Infarction in the ISCHEMIA-CKD Trial.

BACKGROUND: ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) reported an initial invasive treatment strategy did not reduce the risk of death or nonfatal myocardial infarction (MI) compared with a conservative treatment strategy in patients with advanced chronic kidney disease, stable coronary disease, and moderate or severe myocardial ischemia. The cumulative frequency of different MI type after randomization and subsequent prognosis have not been reported. METHODS: MI classification was based on the Third Universal Definition for MI. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary MI definition used cTn (cardiac troponin); both definitions included elevated biomarker-only events with higher thresholds than nonprocedural MIs. The cumulative frequency of MI type according to treatment strategy was determined. The association of MI with subsequent all-cause death and new dialysis initiation was assessed by treating MI as a time-dependent covariate. RESULTS: The 3-year incidence of type 1 or 2 MI with the primary MI definition was 11.2% in invasive treatment strategy and 13.6% in conservative treatment strategy (hazard ratio [HR], 0.66 [95% CI, 0.42-1.02]). Procedural MIs were more frequent in invasive treatment strategy and accounted for 9.8% and 28.3% of all MIs with the primary and secondary MI definitions, respectively. Patients had an increased risk of all-cause death after type 1 MI (adjusted HR, 4.35 [95% CI, 2.73-6.93]) and after procedural MI with the primary (adjusted HR, 2.75 [95% CI, 0.99-7.60]) and secondary MI definitions (adjusted HR, 2.91 [95% CI, 1.73-4.88]). Dialysis initiation was increased after a type 1 MI (HR, 6.45 [95% CI, 2.59-16.08]) compared with patients without an MI. CONCLUSIONS: In ISCHEMIA-CKD, the invasive treatment strategy had higher rates of procedural MIs, particularly with the secondary MI definition, and lower rates of type 1 and 2 MIs. Procedural MIs, type 1 MIs, and type 2 MIs were associated with increased risk of subsequent death. Type 1 MI increased the risk of dialysis initiation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.

Clinical and Quality-of-Life Outcomes Following Invasive vs Conservative Treatment of Patients With Chronic Coronary Disease Across the Spectrum of Kidney Function.

Importance: Prior trials of invasive vs conservative management of chronic coronary disease (CCD) have not enrolled patients with severe chronic kidney disease (CKD). As such, outcomes across kidney function are not well characterized. Objectives: To evaluate clinical and quality-of-life (QoL) outcomes across the spectrum of CKD following conservative and invasive treatment strategies. Design, Setting, and Participants: Participants from the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) and ISCHEMIA-Chronic Kidney Disease (CKD) trials were categorized by CKD stage: stage 1 (estimated glomerular filtration rate [eGFR] 90 mL/min/1.73m2 or greater), stage 2 (eGFR 60-89 mL/min/1.73m2), stage 3 (eGFR 30-59 mL/min/1.73m2), stage 4 (eGFR 15-29 mL/min/1.73m2), or stage 5 (eGFR less than 15 mL/min/1.73m2 or receiving dialysis). Enrollment took place from July 26, 2012, through January 31, 2018, with a median follow-up of 3.1 years. Data were analyzed from January 2020 to May 2021. Interventions: Initial invasive management of coronary angiography and revascularization with guideline-directed medical therapy (GDMT) vs initial conservative management of GDMT alone. Main Outcomes and Measures: The primary clinical outcome was a composite of death or nonfatal myocardial infarction (MI). The primary QoL outcome was the Seattle Angina Questionnaire (SAQ) summary score. Results: Among the 5956 participants included in this analysis (mean [SD] age, 64 [10] years; 1410 [24%] female and 4546 [76%] male), 1889 (32%), 2551 (43%), 738 (12%), 311 (5%), and 467 (8%) were in CKD stages 1, 2, 3, 4, and 5, respectively. By self-report, 18 participants (<1%) were American Indian or Alaska Native; 1676 (29%), Asian; 267 (5%), Black; 861 (16%), Hispanic or Latino; 18 (<1%), Native Hawaiian or Other Pacific Islander; 3884 (66%), White; and 13 (<1%), multiple races or ethnicities. There was a monotonic increase in risk of the primary composite end point (3-year rates, 9.52%, 10.72%, 18.42%, 34.21%, and 38.01% respectively), death, cardiovascular death, MI, and stroke in individuals with higher CKD stages. Invasive management was associated with an increase in stroke (3-year event rate difference, 1%; 95% CI, 0.3 to 1.7) and procedural MI (1.6%; 95% CI, 0.9 to 2.3) and a decrease in spontaneous MI (-2.5%; 95% CI, -3.9 to -1.1) with no difference in other outcomes; the effect was similar across CKD stages. There was heterogeneity of treatment effect for QoL outcomes such that invasive management was associated with an improvement in angina-related QoL in individuals with CKD stages 1 to 3 and not in those with CKD stages 4 to 5. Conclusions and Relevance: Among participants with CCD, event rates were inversely proportional to kidney function. Invasive management was associated with an increase in stroke and procedural MI and a reduced risk in spontaneous MI, and the effect was similar across CKD stages with no difference in other outcomes, including death. The benefit for QoL with invasive management was not observed in individuals with poorer kidney function.

Prognostic Impact of Cardiovascular Versus Noncardiovascular Hospitalizations in Heart Failure With Preserved Ejection Fraction: Insights From TOPCAT.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction are commonly admitted to the hospital for both cardiovascular (CV) and noncardiovascular (non-CV) reasons. The prognostic implications of non-CV hospitalizations in this population are not well understood. In this study, we aimed to examine the prognostic implications of hospitalizations owing to CV and non-CV reasons in a HF with preserved ejection fraction population. METHODS AND RESULTS: The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) randomized 3445 stable outpatients with chronic HF with a left ventricular ejection fraction of 45% or greater and either prior hospitalization for HF or elevated natriuretic peptides to treatment with spironolactone or placebo. Hospitalizations for any cause were reported by investigators during study follow-up and characterized according to prespecified category causes. This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n = 1767), in which 2973 hospitalizations were observed in 1062 subjects (60%) over a mean follow-up of 3.3 years of study follow-up, of which 1474 (49%) were ascribed to CV causes. Among 1056 first hospitalizations, 478 (45%) were for CV reasons and 578 (55%) for non-CV reasons. Mortality rates were lowest for participants not hospitalized during the trial (3.2 per 100 patient-years [PY]), but similarly elevated after first hospitalization for CV and non-CV reasons (11.0 per 100 PY vs 12.6 per 100 PY, respectively; P = .24). Among those hospitalized for CV reasons, mortality rates were similar after hospitalization for HF and non-CV related reasons (15.2 per 100 PY vs 12.6 per 100 PY; P = .23). Recurrent hospitalization, whether owing to CV or non-CV causes, was associated with a heightened risk for subsequent mortality, with similar death rates after hospitalization twice for CV reasons (18.5 per 100 PY), twice for non-CV reasons (21.6 per 100 PY), or once each for CV and non-CV reasons (18.4 per 100 PY). CONCLUSIONS: Among patients with HF with preserved ejection fraction, hospitalization for any cause is associated with a heightened risk for postdischarge mortality, with an even higher risk associated with recurrent hospitalization. Given the high burden of non-CV hospitalizations in this population, the targeted management of comorbid medical illness may be critical to decreasing morbidity and mortality.

Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD.

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.

Geriatric Cardiology: Coming of Age.

Older adults with cardiovascular disease (CVD) contend with deficits across multiple domains of health due to age-related physiological changes and the impact of CVD. Multimorbidity, polypharmacy, cognitive changes, and diminished functional capacity, along with changes in the social environment, result in complexity that makes provision of CVD care to older adults challenging. In this review, we first describe the history of geriatric cardiology, an orientation that acknowledges the unique needs of older adults with CVD. Then, we introduce 5 essential principles for meeting the needs of older adults with CVD: 1) recognize and consider the potential impact of multicomplexity; 2) evaluate and integrate constructs of cognition into decision-making; 3) evaluate and integrate physical function into decision-making; 4) incorporate social environmental factors into management decisions; and 5) elicit patient priorities and health goals and align with care plan. Finally, we review future steps to maximize care provision to this growing population.

Association of Physical Activity With Maximal and Submaximal Tests of Exercise Capacity in Middle- and Older-Aged Adults.

Although physical activity (PA) is an important determinant of exercise capacity, the association between these constructs is modest. The authors investigated the associations of self-reported and objectively measured PA with maximal and submaximal tests of exercise capacity. Participants aged ≥40 years (N = 413; 49.6% female) completed a PA questionnaire, wore a uniaxial accelerometer (5.2 ± 1.1 days), and performed maximal (cardiopulmonary exercise test [CPET]) and submaximal (long-distance corridor walk) tests with indirect calorimetry (oxygen consumption, V˙O2). Linear regression models were fitted to assess the variation in exercise capacity explained (partial eta squared, η2) by PA variables. Accelerometer-measured vigorous (η2 = 22% female; η2 = 16% male) and total PA (η2 = 17% female; η2 = 13% male) explained the most variance in CPET V˙O2 (p < .001). All η2 values were lower for long-distance corridor walk V˙O2 (η2 ≤ 11%). Age contributed more to CPET V˙O2 than any PA variable in males (η2 = 32%), but not in females (η2 = 19%). Vigorous and total PA play important roles in CPET V˙O2 in mid to late life.

Effects of music on the cardiovascular system.

Although music is predominantly utilized for religious, enjoyment or entertainment purposes, it is gradually emerging as a promising non-pharmacological intervention for improving health outcomes in both healthy and diseased populations, especially in those with cardiovascular diseases. As such, music of various genres and types has been postulated to possess features that stimulate or inhibit the autonomic nervous system, which leads to variable effects on cardiovascular function. However, music intervention has not been adequately explored as a cardiovascular therapeutic modality due to the lack of extensive studies with quality methodology. Thus, the aim of this systematic review is to explore the available literature on the effect of music on the cardiovascular system, discuss the limitations of current research, and suggest future directions in this field.

Ischemia and no obstructive coronary arteries in patients with stable ischemic heart disease.

A large proportion of patients with suspected obstructive coronary artery disease (CAD) is found to have ischemia with no obstructive coronary artery disease (INOCA). Based on current evidence, these patients are at increased risk of adverse cardiovascular events, even though they have no obstructive CAD. Importantly, INOCA is associated with recurrent clinical presentations with chest pain, impaired functional capacity, reduced health-related quality of life, and high healthcare costs. Underlying coronary microvascular dysfunction (CMD), through endothelium-dependent and independent mechanisms contribute to these adverse outcomes in INOCA. While non-invasive and invasive diagnostic testing has typically focused on identification of obstructive CAD in symptomatic patients, functional testing to detect coronary epicardial and microvascular dysfunction should be considered in those with INOCA who have persistent angina. Current diagnostic methods to clarify functional abnormalities and treatment strategies for epicardial and/or microvascular dysfunction in INOCA are reviewed.