Elevated sympathetic-mediated vasoconstriction at rest but intact functional sympatholysis during exercise in heart failure with reduced ejection fraction.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) have exaggerated sympathoexcitation and impaired peripheral vascular conductance. Evidence demonstrating consequent impaired functional sympatholysis is limited in HFrEF. This study aimed to determine the magnitude of reduced limb vascular conductance during sympathoexcitation and whether functional sympatholysis would abolish such reductions in HFrEF. METHODS: Twenty patients with HFrEF and 22 age-matched controls performed the cold pressor test (left foot 2-min in -0.5[1] °C water) alone (CPT) and with right handgrip exercise (EX+CPT). Right forearm vascular conductance (FVC), forearm blood flow (FBF), and mean arterial pressure (MAP) were measured. RESULTS: Patients with HFrEF had greater decreases in %ΔFVC and %ΔFBF during CPT (both P<0.0001) but not EX+CPT (P=0.449, P=0.199) compared to controls, respectively. %ΔFVC and %ΔFBF decreased from CPT to EX+CPT in patients with HFrEF (both P<0.0001) and controls (P=0.018, P=0.015), respectively. MAP increased during CPT and EX+CPT in both groups (all P<0.0001). MAP was greater in controls compared to patients with HFrEF during EX+CPT (P=0.025) but not CPT (P=0.209). CONCLUSIONS: Acute sympathoexcitation caused exaggerated peripheral vasoconstriction and reduced peripheral blood flow in patients with HFrEF. Handgrip exercise abolished sympathoexcitatory-mediated peripheral vasoconstriction and normalized peripheral blood flow in patients with HFrEF. These novel data reveal intact functional sympatholysis in the upper limb and suggest exercise-mediated, local control of blood flow is preserved when cardiac limitations that are cardinal to HFrEF are evaded with dynamic handgrip exercise.

Muscle metaboreflex control of left ventricular systolic function in heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6 min of isometric handgrip exercise followed by 6-min of brachial postexercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi), and global longitudinal strain (GLS) were measured by two- and four-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. SVi decreased during MMA in HFrEF (P = 0.037) but not in controls (P = 0.392). ESVi (P = 0.007) and heart rate (P < 0.001) increased during MMA in HFrEF but not controls (P ≥ 0.170). TPR (P = 0.021) and MAP (P < 0.001) increased during MMA in both groups. Cardiac output (P = 0.946), EDVi (P = 0.177), and GLS (P = 0.619) were maintained from rest to MMA in both groups. Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.NEW & NOTEWORTHY Stroke volume decreases and end-systolic volume increases during muscle metaboreflex activation in patients with heart failure with reduced ejection fraction (HFrEF), suggesting impaired contractile reserve during muscle metaboreflex activation in patients with HFrEF. Total peripheral resistance increases similarly during muscle metaboreflex activation in patients with HFrEF compared to controls, indicating normal levels of peripheral vasoconstriction during muscle metaboreflex activation in patients with HFrEF.

Heart failure following oncological treatment.

PURPOSE OF REVIEW: The aim of this review is to give the reader an up-to-date overview of the progress made in the burgeoning field of cardio-oncology, encompassing oncological treatments conferring risk, prediction strategies to identify patients at risk, imaging and biomarker monitoring for emergent or subclinical toxicity and prevention in primary and secondary settings with a focus on heart failure. RECENT FINDINGS: The rapid recent advances in cancer management, particularly with the expansion of targeted and immunotherapies, have led to substantial improvements in outcome, but have also added to the potential causes of cardiac toxicity, which can lead to heart failure. Against this, there has been progression in the field of imaging for cardiac toxicity, identification of at-risk individuals and the clarification of the role of therapy for prevention and treatment of cardiac toxicity. SUMMARY: The findings described in this review provide guidance to clinicians in order to direct monitoring strategy and therapy choice, both in the individual with preexisting cardiac comorbidities and in those predicted to be at the highest risk of cardiac toxicity wherever therapy elements carrying cardiac risk are considered oncologically appropriate.

Appropriate Use Criteria for Cardiac Computed Tomography: Does Computed Tomography Have Incremental Value in All Appropriate Use Criteria Categories?

PURPOSE: Cardiac imaging expenditures have come under scrutiny, and a focus on appropriate use criteria (AUC) has arisen to ensure cost-effective resource utilization. Although AUC has been developed by clinical experts, it has not undergone rigorous quality assurance testing to ensure that inappropriate indications for testing yield little clinical benefit. The objective of the study was to evaluate the potential incremental prognostic value of coronary computed tomographic angiography (CCTA) in the different AUC categories. MATERIALS AND METHODS: Consecutive patients enrolled into a cardiac CT Registry were collated. Patient indications were reviewed and based on the 2010 AUC (appropriate, uncertain, and inappropriate). Patients were followed-up for death, myocardial infarction (MI), and late revascularization, with the primary composite endpoint being cardiac death, nonfatal MI, and late revascularization. The prognostic value of CCTA over clinical variables in each of the AUC categories was assessed. RESULTS: Indications for CCTA were appropriate, uncertain, and inappropriate in 1284 (66.5%), 312 (16.2%), and 334 (17.3%) patients, respectively. Rates of all-cause of death, cardiac death, nonfatal MI, and late revascularization were similar across patients with appropriate, uncertain, and inappropriate indications for CCTA. Moreover, in each AUC category, CCTA had incremental prognostic value over a routine clinical risk score (National Cholesterol Education Program) with hazard ratios of 9.98, 7.39, and 5.61. CONCLUSIONS: CCTA has incremental prognostic value in all AUC categories, even when the reason for the study was deemed "inappropriate." This suggests that CCTA may still have clinical value in "inappropriate" indications and that further quality assurance AUC studies are needed.

Appropriate Use Criteria for Cardiac Computed Tomography: Impact on Diagnostic Utility.

BACKGROUND: Appropriate Use Criteria (AUC) guidelines for cardiac computed tomography (CCT) were developed to limit testing to reasonable clinical settings. However, significant testing is still done for inappropriate indications. This study investigates the impact of AUC on evaluability of CCT to determine if inappropriate tests result in a greater proportion of nondiagnostic results. METHODS: Investigators reviewed the medical records of 2417 consecutive patients who underwent CCT at the University of Ottawa Heart Institute. We applied the 2010 AUC and classified them as appropriate, inappropriate, or uncertain. Unclassifiable tests, as well as those with uncertain appropriateness, were excluded from the final analysis. Cardiac computed tomography results were classified as diagnostic if (1) all coronary segments were visualized, evaluable, and without obstructive stenosis; or (2) obstructive coronary artery disease with greater than 50% diameter stenosis in at least 1 coronary artery. All other test results were considered nondiagnostic. RESULTS: Of the 1984 patients included in the final analysis, 1522 patients (76.7%) had indications that were appropriate, whereas the remaining 462 (23.3%) were inappropriate. Inappropriate tests resulted in a higher rate of nondiagnostic results compared with appropriate CCT (9.0% vs 6.2%, P = 0.034). Inappropriate tests also had significantly more studies with nonevaluable segments than appropriate tests (24.5% vs 16.4%, P < 0.001) and were more likely to reveal obstructive coronary disease than appropriate CCT (50.5% vs 32.7%, P < 0.001). CONCLUSIONS: Cardiac computed tomography done for inappropriate indications may be associated with lower diagnostic yield and could impact future downstream resource utilization and health care costs.

Using coronary calcification to exclude an ischemic etiology for cardiomyopathy: A validation study and systematic review.

BACKGROUND: Preliminary data suggests the absence of coronary artery calcification (CAC) excludes ischemic etiologies of cardiomyopathy. We prospectively validate and perform a systematic review to determine the utility of an Agatston score=0 to exclude the diagnosis of ischemic cardiomyopathy. METHODS AND RESULTS: Patients with newly diagnosed LV dysfunction were prospectively enrolled. Patients underwent CAC imaging and were followed until an etiologic diagnosis of cardiomyopathy was made. Eighty-two patients were enrolled in the study and underwent CAC imaging with 81.7% patients having non-ischemic cardiomyopathy. An Agatston score=0 successfully excluded an ischemic etiology for cardiomyopathy with a specificity of 100% (CI: 74.7-100%) and a positive predictive value of 100% (CI: 85.0%-100%). A systematic literature review was performed and studies were deemed suitable for inclusion if: 1) patients with CHF, cardiomyopathy or LV dysfunction were enrolled, 2) underwent CAC imaging and patients were assessed for an Agatston score=0 or the absence of CAC, and 3) the final etiologic diagnosis (ischemic or non-ischemic) was provided. Eight studies provided sufficient information to calculate operating characteristics for an Agatston score=0 and were combined with our validation cohort for a total of 754 patients. An Agatston score=0 excluded ischemic cardiomyopathy with specificity and positive predictive values of 98.4% (CI: 95.6-99.5%), and 98.3% (CI: 95.5-99.5%), respectively. CONCLUSIONS: In patients with cardiomyopathy of unknown etiology, an Agatston score=0 appears to rule out an ischemic etiology. A screening CAC may be a simple and cost-effective method of triaging patients, identifying those who do and do not need additional CAD investigations.

Noninvasive imaging in acute myocarditis.

PURPOSE OF REVIEW: The gold standard for diagnosing acute myocarditis is endomyocardial biopsy, but it is highly invasive and can result in serious complications. Noninvasive imaging has an essential role in the management of suspected acute myocarditis. In this article, we aim to review the role of various imaging techniques in acute myocarditis. RECENT FINDINGS: Newer methods such as strain and strain rate imaging using speckle tracking have emerged as an adjunctive echocardiographic parameter of myocardial dysfunction. The latest advancements in cardiovascular magnetic resonance (CMR) techniques have allowed quantitative T1 and T2 mappings that aim to quantify the areas of edematous myocardium and also address some of the limitations of traditional techniques as viable tools. An automated method for calculating late gadolinium enhancement by CMR has been developed in recent years. 18-Fluorodeoxyglucose PET is increasingly being used to assist in the diagnosis of myocarditis associated with cardiac sarcoidosis. SUMMARY: Echocardiography remains an essential and most commonly used initial investigation in suspected myocarditis. Due to the recent technological hardware and software advancements in CMR technology, CMR continues to occupy a pole position amongst all the other imaging modalities. The utility of cardiac computed tomography is less clear.

The prognostic role of right ventricular function in left ventricular disease in the setting of cardiac resynchronization therapy.

PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) offers a new therapeutic approach for treating patients with ventricular dyssynchrony and moderate-to-severe heart failure (HF). The impact of right ventricular dysfunction on global cardiac function remains imperfectly understood despite increasing research on right ventricular function as it pertains to long-term outcomes in HF. In this article, we aim to review the prognostic role of right ventricular function in the setting of CRT. RECENT FINDINGS: Right ventricular dysfunction has emerged as a strong prognostic predictor of poor clinical outcomes in HF patients with CRT. The presence of right ventricular dysfunction at baseline is associated with poor prognosis and CRT response. Preliminary data indicate that CRT may have a positive influence on right ventricular remodeling and function. SUMMARY: CRT guidelines continue to be optimized on the basis of emerging data. The prognostic role of right ventricular dyssynchrony and right ventricular response to CRT will further contribute to the understanding of this topic and the identification of HF populations that will benefit from this therapy. As the impact of right ventricular function on global cardiopulmonary function remains imperfectly understood, ongoing research on right ventricular function in HF patients with CRT and its implication for long-term outcome is required. It is, however, clear that right ventricular function is a prognostic marker of response to CRT and adverse long-term outcome. Conversely, recent data indicate that CRT may in turn influence right ventricular remodeling and function.

Heart failure with preserved ejection fraction: current understanding and emerging concepts.

PURPOSE OF REVIEW: Heart failure is a major health problem with significant morbidity and mortality. Although impressive advances in treatment and reduction in mortality have marked heart failure with reduced ejection fraction (HFrEF), the mortality in patients with heart failure with preserved ejection fraction (HFpEF), which accounts for nearly half of heart failure cases, has remained unchanged. This may be because of the lack of consistent diagnostic criteria and limited understanding of the pathophysiology of HFpEF, and thus appropriate treatment options. RECENT FINDINGS: Recent data suggest that HFpEF consists of multiple abnormalities rather than a distinct entity. Advances in testing have improved diagnosis, but further validation is required. The discoveries of new pathological abnormalities have identified potential new drug therapy targets. Traditional agents with strong evidence in HFrEF have proved unsuccessful in HFpEF. Newer agents such as angiotensin receptor neprilysin inhibitor, sildenafil, and ivabradine have demonstrated benefits without improving mortality. Lastly, as HFpEF patients are older with more comorbidities, alternate endpoints to survival benefit should be considered. SUMMARY: Although enormous strides have been made in understanding the pathophysiology and refining the diagnostic criteria of HFpEF, there is currently no pharmacological therapy with mortality benefits. Further characterization and the recruitment of more homogeneous patient populations will be essential to identify effective treatments.