Strengths and weaknesses of alternative noninvasive imaging approaches for microvascular ischemia.

Structural and functional abnormalities of coronary microvasculature are highly prevalent in several clinical settings and often associated with worse clinical outcomes. Therefore, there is a growing interest in the detection and treatment of this, often overlooked, disease. Coronary angiography allows the assessment of the Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). However, the measurement of these parameters is not always feasible because of limited technical availability and the need for a cardiac catheterization with a small but real risk of potential complications. Recent advances in non-invasive imaging techniques allow the assessment of coronary microvascular function with good accuracy and reproducibility. The objective of this review is to discuss the strengths and weaknesses of alternative non-invasive approaches used in the diagnosis of coronary microvascular dysfunction (CMD), highlighting the most recent advances for each imaging modality.

Predictors of in-hospital mortality in critically ill patients with COVID-19: a large dual tertiary centre study.

OBJECTIVES: The aim of this study was to investigate the relationship of echocardiographic parameters, laboratory findings and clinical characteristics with in-hospital mortality in adult patients with COVID-19 admitted to the intensive care units (ICU) in two large collaborating tertiary UK centres. DESIGN: Observational retrospective study. SETTING: The study was conducted in patients admitted to the ICU in two large tertiary centres in London, UK. PARTICIPANTS: Inclusion criteria were: (1) patients admitted to the ICU with a COVID-19 diagnosis over a period of 16 weeks. and (2) underwent a transthoracic echocardiogram on the first day of ICU admission as clinically indicated.No exclusion criteria applied.Three hundred patients were enrolled and completed the follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure in this study was in-hospital mortality in patients admitted to the ICU with COVID-19 infection. RESULTS: Older age (HR: 1.027, 95% CI 1.007 to 1.047; p=0.008), left ventricular (LV) ejection fraction<35% (HR: 5.908, 95% CI 2.609 to 13.376; p<0.001), and peak C reactive protein (CRP) (HR: 1.002, 95% CI 1.001 to 1.004, p=0.001) were independently correlated with mortality in a multivariable Cox regression model. Following multiple imputation of variables with more than 5% missing values, random forest analysis was applied to the imputed data. Right ventricular (RV) basal diameter (RVD1), RV mid-cavity diameter (RVD2), tricuspid annular plane systolic excursion, RV systolic pressure, hypertension, RV dysfunction, troponin level on admission, peak CRP, creatinine level on ICU admission, body mass index and age were found to have a high relative importance (> 0.7). CONCLUSIONS: In patients with COVID-19 in the ICU, both severely impaired LV function and impaired RV function may have adverse prognostic implications, but older age and inflammatory markers appear to have a greater impact. A combination of echocardiographic and laboratory investigations as well as demographic and clinical characteristics appears appropriate for risk stratification in patients with COVID-19 who are admitted to the ICU.

Imaging in Women with Heart Failure: Sex-specific Characteristics and Current Challenges.

Cardiovascular disease (CVD) represents a significant threat to women's health. Heart failure (HF) is one CVD that still has an increasing incidence and about half of all cases involve women. HF is characterised by strong sex-specific features in aetiology, clinical manifestation and outcomes. Women are more likely to have hypertensive heart disease and HF with preserved ejection fraction, they experience worse quality of life but have a better overall survival rate. Women's hearts also have unique morphological characteristics that should be considered during cardiovascular assessment. It is important to understand and highlight these sex-specific features to be able to provide a tailored diagnostic approach and therapeutic management. The aim of this article is to review these aspects together with the challenges and the unique characteristics of different imaging modalities used for the diagnosis and follow-up of women with HF.

Imaging Findings of COVID-19-Related Cardiovascular Complications.

Other than respiratory disease, patients with coronavirus disease 2019 (COVID-19) commonly have cardiovascular manifestations, which are recognized as significant risk factors for increased mortality. COVID-19 patients may present with a wide spectrum of clinical presentations ranging from asymptomatic heart disease detected incidentally by cardiac investigations (troponin, BNP, and imaging) to cardiogenic shock and sudden cardiac death. In this broad clinical course, advanced imaging plays an important role in the diagnosis of different patterns of myocardial injury, risk stratification of COVID-19 patients, and in detecting potential cardiac side effects of the current treatments and vaccines against the severe acute respiratory syndrome.

Atrial fibrillation ablation in heart failure: Findings from the ESC-EHRA EORP Atrial Fibrillation Ablation long-term (AFA LT) registry.

BACKGROUND: The current practice of atrial fibrillation ablation (AFA) as a treatment option for atrial fibrillation (AF) in patients with heart failure (HF) across Europe, their clinical profiles and outcomes is still undefined. METHODS: The European Society of Cardiology (ESC) led a prospective observational registry of consecutive patients undergoing AFA, in 27 member countries. The subgroup of patients with HF, followed-up for 1 year, was analyzed and the results are reported. RESULTS: Of the 3582 AF patients in the Registry, 537 (14.9%) had HF. Diabetes, hypertension, hypercholesterolemia, CHA2DS2-VASc score ≥ 2, structural heart disease and persistent AF were more common in HF than non-HF patients (all p < 0.001). However the in-hospital complications were less frequent in HF patients (5.0% vs. 8.2% p = 0.01). Both in-hospital and 1-year outcomes, including 1-year AF recurrence (15.4%) and repeat ablations (9.5%), were similar in both groups. We subdivided HF patients according to their left ventricular ejection fraction (EF) at baseline into reduced (HFrEF, <40%), mid-range (HFmEF, 40-49%), or preserved EF (HFpEF, ≥ 50%). Most patients were HFpEF (n 375, 77%), 72 (15%) were HFmEF and 8% HFrEF. The most frequent underlying conditions in HFpEF were hypertension and ischemic heart disease, while those most common in HFmEF and HFrEF were valvular and dilated cardiomyopathy. CONCLUSION: In routine care in Europe, HF patients represent a minority of patients undergoing AFA, and most belong to the HFpEF phenotype. The limited clinical research on AFA HFpEF patients is reflected by the uncertainty expressed in the current AF Guidelines and Expert statements.

Cardiovascular Magnetic Resonance Parametric Mapping Techniques: Clinical Applications and Limitations.

PURPOSE OF REVIEW: Parametric mapping represents a significant innovation in cardiovascular magnetic resonance (CMR) tissue characterisation, allowing the quantification of myocardial changes based on changes on T1, T2 and T2* relaxation times and extracellular volume (ECV). Its clinical use is rapidly expanding, but it requires availability of dedicated equipment as well as expertise in image acquisition and analysis. This review focuses on the principles of CMR parametric mapping, its current clinical applications, important limitations, as well as future directions of this technique in cardiovascular medicine. RECENT FINDINGS: There is increasing evidence that CMR parametric mapping techniques provide accurate diagnostic and prognostic tools that can be applied to and support the clinical management of patients with a range of cardiovascular disease. The unique capability of CMR myocardial tissue characterisation in cardiovascular diseases has further expanded by the introduction of parametric mapping. Its use in clinical practice presents opportunities but has also limitations.

First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85-9.60]; P<0.001) unadjusted and 4.83 ([95% CI, 2.35-9.95], P<0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, P=0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.

Early Left Ventricular Global Longitudinal Strain Deterioration After Aortic Aneurysm Repair: Impact of Aortic Stiffness.

PURPOSE: To associate the impact of aortic reconstruction using currently available grafts and endografts on pulse wave velocity in patients with abdominal aortic aneurysm (AAA) and to evaluate its effect on early cardiac systolic function indices. MATERIALS AND METHODS: Seventy-three consecutive patients with AAA (mean age 70±8 years; all men) who underwent open (n=12) or endovascular repair (EVAR; n=61) were prospectively enrolled in an observational cohort study. Left ventricular global longitudinal strain (GLS; an important diagnostic and prognostic index of early systolic dysfunction) and carotid-femoral pulse wave velocity (cf-PWV) were estimated 1 week preoperatively, as well as at 1 and 6 months postoperatively. RESULTS: A significant time effect was found for cf-PWV, which showed an increase at 1 month that remained through 6 months (p=0.007). Additionally, a deterioration in GLS values was revealed, with a significant change at 1 month that persisted 6 months later (p<0.001). No significant group effect was observed between EVAR and open repair (p=0.98), and there was no significant interaction (p=0.96). Notably, the difference in GLS between baseline and 6 months significantly correlated with the corresponding changes in cf-PWV (r=0.494, p<0.001). CONCLUSION: AAA repair leads not only to an increase in aortic stiffness, as measured by the increase in pulse wave velocity, but also to reduced cardiac systolic function. Our findings highlight the need for a more intense cardiac surveillance program after aortic reconstruction. Further studies are needed to investigate how this may translate into long-term manifestations of cardiovascular complications and symptomatology.

The Role of Cardiac Magnetic Resonance in Myocardial Infarction and Non-obstructive Coronary Arteries.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) accounts for 5-15% of all presentations of acute myocardial infarction. The absence of obstructive coronary disease may present a diagnostic dilemma and identifying the underlying etiology ensures appropriate management improving clinical outcomes. Cardiac magnetic resonance (CMR) imaging is a valuable, non-invasive diagnostic tool that can aide clinicians to build a differential diagnosis in patients with MINOCA, as well as identifying non-ischemic etiologies of myocardial injury (acute myocarditis, Takotsubo Syndrome, and other conditions). The role of CMR in suspected MINOCA is increasingly recognized as emphasized in both European and American clinical guidelines. In this paper we review the indications for CMR, the clinical value in the differential diagnosis of patients with suspected MINOCA, as well as its current limitations and future perspectives.

Isolated papillary muscle rupture with nonobstructive coronary artery disease, minimal myocardial infarction, and normal wall motion.

Papillary muscle (PM) rupture can usually complicate inferior or posterior myocardial infarctions, but selective PM infarction is extremely rare, and the exact underlying pathophysiological mechanism is not entirely clear. We present a case of PM rupture due to isolated PM infarction in a patient with unobstructed coronary arteries, which could be misdiagnosed as a vegetation or other mass given the absence of regional wall motion abnormalities (RWMAs) on transthoracic echocardiogram. Our case highlights that in patients with severe mitral regurgitation and associated mitral valve mass, the absence of RWMAs should not exclude ischemic PM rupture from differential diagnosis.

Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study.

AIMS: Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. METHODS AND RESULTS: Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: 'DSP/FLNC genotypes' and 'non-DSP/FLNC'. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT. CONCLUSION: DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.

Short-term effects of angiotensin receptor-neprilysin inhibitors on diastolic strain and tissue doppler parameters in heart failure patients with reduced ejection fraction: A pilot trial.

OBJECTIVE: Although sacubitril/valsartan has recently shown its long-term benefits on morbidity and mortality in symptomatic patients with chronic heart failure with reduced ejection fraction (HFrEF), its short-term effects on diastolic function remain uncertain. We sought to assess 30-day effects of sacubitril/valsartan on left ventricular (LV) diastolic paremeters determined by speckle tracking and tissue Doppler imaging (STI and TDI respectively) as well as their association with functional capacity change evaluated by peak oxygen uptake (VO2max) in stable patients with symptomatic HFrEF. METHODS: A total of 35 patients (aged 61 ± 9 years) eligible for sacubitril/valsartan underwent a complete two-dimension (2D) echocardiographic study and a cardiopulmonary exercise test at baseline and 30 days after the initiation of therapy. RESULTS: Significant improvements in ratio of trans-mitral inflow early diastolic velocity E to mitral annulus early diastolic velocity E' (ΔΕ//Ε' = -35.9%, p = 0.001), peak early diastolic strain rate SRE (ΔSRE = +22.5%, p = 0.024) and ratio E/SRE (ΔE/SRE = -33.2%, p = 0.025) were observed after 1-month therapy. Compared with baseline, VO2max also increased significantly by 16.7 % (p = 0.001). Baseline E/SRE and ΔE/SRE were the strongest independent predictors of VO2max improvement (beta = -0.43, p = 0.004 and beta = 0.45, p = 0.021 respectively) in the multivariate analysis. CONCLUSION: Sacubitril/valsartan was associated with early improvement in LV diastolic function determined by TDI and 2D STI. Baseline E/SRE was stronger than standard echocardiographic parameters in predicting the early benefit of sacubitril/valsartan therapy.

Troponin-I levels as a potential prognostic biomarker of sacubitril/valsartan treatment response in heart failure with reduced ejection fraction: Who will benefit most?

BACKGROUND: Despite robust data on the benefits of sacubitril/valsartan (LCZ696) in patients with chronic heart failure with reduced ejection fraction (HFrEF), there is no evidence yet on prespecified predictive markers of its efficacy. Hypothesis The objective of this study was to identify potential prognostic factors of LCZ696 treatment response. METHODS: We included 48 symptomatic patients with chronic HFrEF (left ventricular ejection fraction ≤35%) and New York Heart Association (NYHA) class II/III: Group A (N = 23) received LCZ696 (105 ± 30 mg twice daily), whereas it was not prescribed in group B (N = 25) according to physician's judgment. Analysis of biochemical parameters, cardiopulmonary exercise testing, and echocardiographic evaluation was performed at baseline and 6 months later. RESULTS: The baseline serum troponin-I levels (TnI) and peak oxygen uptake (VO2 max) were positively associated with the increase in VO2 max (ΔVO2 max = +14.11%, P < 0.05 vs group B) after sacubitril/valsartan treatment (r = 0.68, P = 0.001 and r = 0.57, P = 0.004, respectively). Positive correlations were reported between ΔVO2 max and the improvements in the ratio of early diastolic filling to myocardial tissue velocity (ΔE/E') and the tricuspid annular peak systolic velocity (ΔSa) in group A (r = 0.58, P = 0.004 and r = 0.60, P = 0.002, respectively). In multiple regression analysis, ΔVO2 max was correlated significantly with TnI (beta = 0.35, P = 0.048), ΔE/E' (beta = 0.36, P = 0.031) and ΔSa (beta = 0.37, P = 0.035). CONCLUSIONS: TnI levels may be an independent predictive marker of sacubitril/valsartan efficacy in HFrEF.

Myocardial regeneration therapy in heart failure: Current status and future therapeutic implications in clinical practice.

Despite multiple treatment regimens the morbidity and mortality of patients with advanced heart failure (HF) have reached pandemic proportions. In an effort to address the root cause of the problem, curative strategies are increasingly being considered. A case in point is the evolution of regenerative medicine technologies aiming to halt or even reverse progressive organ deterioration in the HF setting. The prevailing unmet clinical needs in HF therapy have provided a major incentive for the development of cell-based treatment strategies, which have shown encouraging results in experimental studies. In turn, this has led to a significant international effort in cell-based clinical trials. In order to translate the promise of biotherapies into clinical benefit many more questions need to be addressed. In this review we analyze current clinical experience regarding cell therapy in the setting of ischemic/nonischemic HF and address key issues that could be a guide for future successful cell-based therapeutic application in HF patients in clinical practice.

Anticoagulation in heart failure without atrial fibrillation: gaps and dilemmas in current clinical practice.

Data from observational and post-hoc analyses suggest that heart failure (HF) itself may be associated with higher risk of thromboembolic events compared to populations without HF. Although oral anticoagulants (OACs) might be a therapeutic option in individual cases, anticoagulation therapy in HF patients in sinus rhythm is not generally recommended, as the implementation of OACs in clinical practice in this HF population is not supported by large randomized clinical trials to date. Indeed, the available data suggest that the risk of major bleeding overshadows the potential anti-thromboembolic benefit of OACs in HF patients in sinus rhythm with no net beneficial effect on mortality rates. In this review we explore the current available evidence for the clinical outcomes of anticoagulation therapy in patients with HF in sinus rhythm, highlighting the current gaps in knowledge, which may guide the design of future randomized clinical trials focusing on the efficacy and safety of anticoagulant therapy in this HF population.