Current Heart Failure Reports

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Online ISSN: 1546-9549
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Purpose of review: This review offers an overview of the evidence in diagnostic and therapeutic applications of remote monitoring implantable devices. Recent findings: Remote monitoring of cardiac implantable devices has become more and more popular in recent years as healthcare is moving towards a more patient centralized system. For heart failure patients with an ICD or pacemaker, there is controversial evidence regarding improvements in the clinical outcome, e.g., reduction of hospitalization rates or overall mortality. New developments as hemodynamic remote monitoring via measurement of the pulmonary artery pressure are promising technical achievements showing encouraging results. In cardiac remote monitoring of syncope and arrhythmias, implantable loop recorder plays an important role in diagnostic algorithms. Although there is controversial evidence according to remote monitoring of implantable devices, its use is rapidly expanding, giving healthcare providers the opportunity to react promptly to worsening of their patients. Adequate evaluation of the data created by remote monitoring systems remains an unsolved challenge of contemporary healthcare services.
 
Cardiotoxicity due to anthracycline: the multiple-hit hypothesis
Purpose of the Review Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. Recent Findings Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. Summary As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD.
 
Cardiac MRI images of a patient with prior thoracic radiation. Late gadolinium enhancement imaging demonstrates patchy, predominantly midwall enhancement in the basal inferolateral wall (arrows in panel A), as well as in the mid and apical inferior walls (arrows in panel B), in a non-ischemic pattern
Purpose of Review As the percentage of patients achieving long-term survival following treatment of their cancer grows, it is increasingly important to understand the long-term toxicities of cancer-directed treatment. In this review, we highlight the recent findings regarding radiation-induced cardiotoxicity across multiple disease sites, with a particular focus on heart failure.Recent FindingsDespite its relative lack of study historically, radiation-induced heart failure has now recently been implicated in several studies of breast cancer, lung cancer, esophageal cancer, and lymphoma as a non-trivial potential consequence of thoracic radiotherapy. Data regarding specific cardiac dosimetric endpoints relevant to cardiotoxicity continue to accumulate.SummaryRadiation-induced heart failure is a rare but significant toxicity of thoracic radiotherapy, that is likely underreported. Important areas for future focus include understanding the interplay between thoracic radiotherapy and concurrent cardiotoxic systemic therapy as well as development of potential mitigation strategies and novel therapeutics.
 
Purpose of Review The purpose of this review was to synthesize the evidence on non-traditional biomarkers from proteomic and metabolomic studies that may distinguish heart failure (HF) with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF) and non-HF. Recent Findings Understanding the pathophysiology of HFpEF continues to be challenging. A number of inflammatory and metabolic biomarkers that have recently been suggested to be involved include C-reactive protein (CRP), interleukin-6 (IL-6), trimethylamine-N-oxide (TMAO), syndecan-1 (SDC-1), nitric oxide (NO), and tumor necrosis factor receptor-1 (TNFR-1). Summary A systematic search was conducted using Medline, EMBASE, and Web of Science with search terms such as “HFpEF,” “metabolomics,” and “proteomics,” and a meta-analysis was conducted. The results demonstrate significantly higher levels of TMAO, CRP, SDC-1, and IL-6 in HFpEF compared to controls without HF and significantly higher levels of TMAO and CRP in HFrEF compared to controls. The results further suggest that HFpEF might be distinguishable from HFrEF based on higher levels of IL-6 and lower levels of SDC-1 and NO. These data may reflect pathophysiological differences between HFpEF and HFrEF.
 
Sarcopenia: EWGSOP2 algorithm for case-finding, making a diagnosis and quantifying severity in practice. DEXA, dual-energy X-ray absorptiometry; BIA, bioimpedance analysis; 6MWT, 6-min walking test; SPPB, short physical performance battery. Modified from Cruz-Jentoft AJ et al. Age Ageing 2019
Purpose of Review Sarcopenia and frailty are common in patients with heart failure (HF) and are strongly associated with prognosis. This review aims to examine promising biomarkers that can guide physicians in identifying sarcopenia and frailty in HF. Recent Findings Traditional biomarkers including C-reactive protein, aminotransaminase, myostatin, and urinary creatinine as well as novel biomarkers including microRNAs, suppression of tumorigenicity 2 (ST2), galectin-3, and procollagen type III N-terminal peptide may help in predicting the development of sarcopenia and frailty in HF patients. Among those biomarkers, aminotransferase, urinary creatinine, and ST2 predicted the prognosis in HF patients with sarcopenia and frailty. Summary This review outlines the current knowledge of biomarkers that are considered promising for diagnosing sarcopenia and frailty in HF. The listed biomarkers might support the diagnosis, prognosis, and therapeutic decisions for sarcopenia and frailty in HF patients.
 
Electrocardiographic abnormalities in patients with different LVNC structural phenotypes on cardiac magnetic resonance imaging. (a) ECG fulfills voltage criteria for left ventricular hypertrophy; deep T-wave inversion in leads V4–V6 with associated ST segment depression; minor T-wave inversion in leads I, II, avL and aVF; biphasic T-wave noted in lead 3 with a proceeding convex ST segment. (b) Left axis deviation with minor T-wave inversion in lateral leads (leads I, aVL, V4–V6). (c) Minor T-wave inversion in V1–V3. (d) Fragmentation of QRS morphology in leads III, V3 and V4. (e) Minor T-wave inversion in leads II, III, aVF and V4–V6. There is also an isolated ventricular extra-systole. (f) Normal ECG with no repolarization changes. (g) Deep R/S complexes in leads V2–V3
Twelve-lead electrocardiogram in two cases of augmented left ventricular trabeculation (echocardiographic apical 4-chamber view). Thirty-year-old male with familial LVNC. Black arrows indicate non-specific repolarization abnormalities in limb leads, Goldberger’s leads and lateral precordial leads (a). Twenty-two-year-old cyclist with increased left ventricular trabeculation. ECG is normal with high, but physiological T-waves (red arrows) (b)
Contribution of the ECG in the diagnostic workup of patients with hypertrabeculation in different physiological or disease states
Purpose of the Review Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC. Recent Findings ECG abnormalities have been reported in 75–94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. Summary The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC.
 
PRISMA flow chart of study inclusion
A Posterior distribution of absolute risk difference for all-cause mortality; B posterior distribution of absolute risk difference for cardiovascular mortality; C posterior distribution of absolute risk difference for cardiovascular admission; D Posterior distribution of absolute risk difference for heart failure admission
Purpose of Review To evaluate remote monitoring using implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) devices as an adjunctive tool to the traditional care of patients with heart failure (HF). Recent Findings We included 11 trials encompassing 5965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods. The ARD for mortality was centered at − 0.01 (95% CrI: − 0.03; 0.01, Tau: 0.02), with an 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at − 0.03 (95% CrI: − 0.11; 0.05, Tau: 0.10), with an 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. Summary ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause and cardiovascular mortality compared with standard care alone.
 
Purpose of Review Heart failure (HF) after right ventricular myocardial infarction (RVMI) is common and complicates its clinical course. This review aims to provide a current overview on the characteristic features of RV failure with focus on acute management. Recent Findings While HF after RVMI is classically seen after acute proximal right coronary artery occlusion, RV dysfunction may also occur after larger infarctions in the left coronary artery. Because of its different anatomy and physiology, the RV appears to be more resistant to permanent infarction compared to the LV with greater potential for recovery of ischemic myocardium. Hypotension and elevated jugular pressure in the presence of clear lung fields are hallmark signs of RV failure and should prompt confirmation by echocardiography. Management decisions are still mainly based on small studies and extrapolation of findings from LV failure. Early revascularization improves short- and long-term outcomes. Acute management should further focus on optimization of preload and afterload, maintenance of sufficient perfusion pressures, and prompt management of arrhythmias and concomitant LV failure, if present. In case of cardiogenic shock, use of vasopressors and/or inotropes should be considered along with timely use of mechanical circulatory support (MCS) in eligible patients. Summary HF after RVMI is still a marker of worse outcome in acute coronary syndrome. Prompt revascularization, careful medical therapy with attention to the special physiology of the RV, and selected use of MCS provide the RV the time it needs to recover from the ischemic insult.
 
Purpose of Review The heterogeneity of heart failure with preserved ejection fraction (HFpEF) is responsible for the limited success of broad management strategies. The role of biomarkers has been evolving helping to provide insight into the diversity of pathophysiology, prognosis, and potential targets for treatments. We will review the role of traditional and novel biomarkers in diagnosing, prognosticating, and evolving the management of patients with HFpEF. As circulating biomarker discovery rapidly evolves, we will explore technology for new biomarker discovery with examples of successful implementation. Recent Findings Besides cardiac-specific biomarkers (natriuretic peptides and troponin), other novel nonspecific biomarkers increasingly identify the diversity of pathophysiological mechanisms of HFpEF including inflammation, fibrosis, and renal dysfunction. Newer approaches have provided increasing granularity providing opportunities to integrate large amounts of information from proteomics and genomics as biomarkers of interest in HFpEF. Summary HFpEF has been marked with failure of many medications to show benefit, whether measuring single targeted biomarkers or broader targeted discovery proteomics or genomic circulating biomarkers are providing increasing opportunities to better understand and manage HFpEF patients.
 
Differences in pharmacokinetic and pharmacodynamic in male and female are summarized. CYP, cytochrome P; F, female; M, male
Analyses for male and female subgroups in the main randomized controlled trials evaluating the efficacy of heart failure drugs. ACE, angiotensin I converting enzyme; ARBs, angiotensin II receptor blockers; ARNi, angiotensin II receptor neprilysin inhibitors; CI, confidence interval; HR, hazard ratio; MRA, mineralocorticoid receptor antagonist; n.s., not significant interaction; SGLT2i, inhibitors of type 2 renal sodium-glucose co-transporter. *Composite end-point: Cardiovascular death or first admission for heart failure; †death from cardiovascular causes or hospitalization for heart failure; ‡composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death; #for PARADIGM-HF sacubitril/valsartan vs. enalapril
Purpose of Review Over the last decades, several classes of drugs have been introduced for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). Their use has been supported by randomized controlled trials that have demonstrated improved patient outcomes. However, these trials enrolled a small number of female patients and sometimes have reported gender-related differences regarding the efficacy of the treatments. The aim of this review is to revise the available data about the influence of gender on the optimal treatment and drug dose in patients with HFrEF. Recent Findings Several gender-related differences in terms of pharmacokinetic and pharmacodynamic characteristics of the drugs have been described. These characteristics could be responsible for a different response and tolerability in men and women also when current recommended treatment of HFrEF is considered. Some studies have shown that, in women, lower doses of beta-blockers and inhibitors of renin angiotensin aldosterone system could be equally effective than higher doses in men, whereas sacubitril/valsartan could exert its favorable effect at greater values of left ventricular ejection fraction. Summary Although there is evidence about differences in the response to treatment of HFrEF in men and women, this has not been sufficient for differentiating current recommended therapy. Further studies should better clarify if the treatment of HFrEF should be based also on the patients’ gender.
 
Schema of HFpEF demonstrating pathophysiological heterogeneity. While myocardial changes lead to an abnormal ventricular pressure–volume relationship and elevated filling pressure, multiple cardiovascular and non-cardiovascular and general pathogenic mechanisms influence the incidence and outcomes of HFpEF and lead to marked heterogeneity of disease
Proposed scheme for defining clinical phenotypes of HFpEF and treatment strategies. We propose a flowchart that represents a likely future schema for phenotyping patients including initial evaluation with history, physical exam, cardiac imaging, and labs with biomarkers. Once data is input through ML methods, patients will be grouped into a sub-phenotype and receive targeted therapeutics
Major clustering studies to resolve heterogeneity of HFpEF
Sub-phenotypes of HFpEF derived by clustering
Purpose of Review Heart failure with preserved ejection fraction (HFpEF) imposes a significant burden on society and healthcare. The lack in efficacious therapies is likely due to the significant heterogeneity of HFpEF. In this review, we define various phenotypes based on underlying comorbidities or etiologies, discuss phenotypes arrived at by novel methods, and explore therapeutic targets. Recent Findings A few studies have used machine learning methods to uncover sub-phenotypes within HFpEF in an unbiased manner based on clinical features, echocardiographic findings, and biomarker levels. Summary We synthesized the literature and propose three broad phenotypes: (1) young, with few comorbidities, usually obese and with low natriuretic peptide levels, (2) obese with substantive cardiometabolic burden and comorbidities and impaired ventricular relaxation, (3) old, multimorbid, with high rates of atrial fibrillation, renal and coronary artery disease, chronic obstructive pulmonary disease, and left ventricular hypertrophy. We also propose potential therapeutic strategies for these phenotypes.
 
Hemodynamic cardiorenal interactions in left and right heart failure. Right side: traditional “low flow” hypothesis of the development of worsening renal function in heart failure due to renal vasoconstriction and hypoperfusion leading to tubular hypoxia and necrosis. Left side: concept of “congestive nephropathy” primarily leading worsening renal function in heart failure according to current expert opinion. Heart failure-induced backward transmission results in increased central venous pressure and renal venous congestion with subsequent impaired renal function. CO, cardiac output; CVP, central venous pressure; GFR, glomerular filtration rate; HF, heart failure; LHF, left heart failure; LV, left ventricle; RAAS, renin–angiotensin–aldosterone system; RHF, right heart failure; RV, right ventricle; WRF, worsening renal function.
Adapted from Schefold, J. C. et al. (2016) Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat. Rev. Nephrol. 10.1038/nrneph.2016.113 and from Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure. Circulation 2020;141:678–693
Purpose of Review Since CRS is critically dependent on right heart function and involved in interorgan crosstalk, assessment and monitoring of both right heart and kidney function are of utmost importance for clinical outcomes. This systematic review aims to comprehensively report on novel diagnostic and therapeutic paradigms that are gaining importance for the clinical management of the growing heart failure population suffering from CRS. Recent Findings Cardiorenal syndrome (CRS) in patients with heart failure is associated with poor outcome. Although systemic venous congestion and elevated central venous pressure have been recognized as main contributors to CRS, they are often neglected in clinical practice. The delicate hemodynamic balance in CRS is particularly determined by the respective status of the right heart. Summary The consideration of hemodynamic and CRS profiles is advantageous in tailoring treatment for better preservation of renal function. Assessment and monitoring of right heart and renal function by known and emerging tools like renal Doppler ultrasonography or new biomarkers may have direct clinical implications.
 
Well defined adverse systemic effects associated with short-term and long-term hydroxychloroquine treatment. HCQ indicates hydroxychloroquine. Figure created in Biorender
QT prolongation in patients with COVID-19 treated with hydroxychloroquine. Predisposing risk factors to QT prolongation in patients with COVID-19 (A). Electrophysiological mechanism of action of QT prolongation with hydroxychloroquine treatment (B). HCQ inhibition of the potassium rectifier current (Ikr) through inhibition of the human ether-a-go-go-related gene (hERG) channel leads to increased action potential duration and subsequent QT prolongation. QT prolongation may ultimately lead to Torsades de Pointes. HCQ indicates hydroxychloroquine; hERG, human ether-a-go-go-related gene; AP, action potential. Figure created in Biorender
Purpose of Review The coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19. Recent Findings Early clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur. Summary Although, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.
 
Increased risk of mortality associated with hospitalisation with worsening heart failure. Few patients die during hospitalisation (red), the majority die following discharge (brown), especially during the vulnerable phase during which the risk is many times higher compared to similar patients who are never hospitalised (yellow)
Conceptual frameworks of acute heart failure presentations. Patients may be classified based on perfusion (warm or cold) and congestion (dry or wet) or based on pathophysiological mechanisms
Ongoing reassessment of goals-of-care. Hospitalisation should be viewed as an opportunity to continually reassess the goals-of-care. Management of decompensation, optimisation of prognostic therapies, and the concurrent palliative approach should be considered
Purpose of Review The distinction between ‘acute’ and ‘chronic’ heart failure persists. Our review aims to explore whether reclassifying heart failure decompensation more accurately as an event within the natural history of chronic heart failure has the potential to improve outcomes. Recent Findings Although hospitalisation for worsening heart failure confers a poor prognosis, much of this reflects chronic disease severity. Most patients survive hospitalisation with most deaths occurring in the post-discharge ‘vulnerable phase’. Current evidence supports four classes of medications proven to reduce cardiovascular mortality for those who have heart failure with a reduced ejection fraction, with recent trials suggesting worsening heart failure events are opportunities to optimise these therapies. Summary Abandoning the term ‘acute heart failure’ has the potential to give greater priority to initiating proven pharmacological and device therapies during decompensation episodes, in order to improve outcomes for those who are at the greatest risk.
 
Pathologic specimens. A Pathologic specimen of the right ventricle with the free wall removed to demonstrate the 3 anatomic regions [9]. B Pathologic specimen of the heart cut transversely demonstrating the crescent shape of the right ventricle [9]. Image from Warnes [9] reproduced with permission. Please remove Photo courtesy of Dr. W. D. Edwards, consultant in pathology, Mayo Clinic
Four-chamber view on a transthoracic echocardiogram shows the intra-atrial baffles seen in a patient with D-loop TGA post atrial switch where baffles are used to restore physiological circulation. A An atrial baffle diverts blood from both vena cava across to the mitral valve and LV (blue arrow is in the systemic venous baffle), which ejects blood to the PA. B The oxygenated pulmonary venous blood returns to the tricuspid valve and systemic RV (red arrow is in the pulmonary venous baffle), which ejects blood to the aorta. C Apical short-axis view on a transthoracic echocardiogram shows a dilated and hypertrophied systemic RV where the interventricular septum bulges into the “banana” shaped—a finding expected in a patient with systemic RV post atrial switch repair
Pathophysiological pathways of systemic right ventricular (RV) dysfunction from Winter [24]. The pathophysiology of systemic RV dysfunction is multifactorial and includes arrhythmias, tricuspid valve regurgitation, myocar-dial fibrosis, and myocardial ischemia. Image from Winter [24] reproduced with permission
Pathologic specimen cut in the 4-chamber plane from a patient with Ebstein anomaly from Warnes [9]. The tricuspid valve is displaced markedly inferiorly, and the right ventricular wall is extremely thin. Image from Warnes [9] reproduced with permission. Please remove Photo courtesy of Dr. W. D. Edwards, consultant in pathology, Mayo Clinic
Purpose of Review The right ventricle (RV) and left ventricle (LV) have different developmental origins, which likely plays a role in their chamber-specific response to physiological and pathological stress. RV dysfunction is encountered frequently in patients with congenital heart disease (CHD) and right heart abnormalities emerge from different causes than increased afterload alone as is observed in RV dysfunction due to pulmonary hypertension (PH). In this review, we describe the developmental, structural, and functional differences between ventricles while highlighting emerging therapies for RV dysfunction. Recent Findings There are new insights into the role of fibrosis, inflammation, myocyte contraction, and mitochondrial dynamics in the pathogenesis of RV dysfunction. We discuss the current state of therapies that may potentially improve RV function in both experimental and clinical trials. Summary A clearer understanding of the differences in molecular alterations in the RV compared to the LV may allow for the development of better therapies that treat RV dysfunction.
 
Effective decongestion is often a balance of factors that will contribute to decongestion and those that will lead to worsening renal function. Clinicians must assess the cause of decompensation to help guide treatment
Purpose of the Review Progressive intravascular, interstitial, and alveolar fluid overload underlies the transition from compensated to acutely decompensated heart failure and loop diuretics are the mainstay of treatment. Adverse effects and resistance to loop diuretics received much attention while the contribution of a depressed cardiac output to diuretic resistance was downplayed. Recent Findings Analysis of experience with positive inotropic agents, especially dobutamine, indicates that enhancement of cardiac output is not consistently associated with increased renal blood flow. However, urinary output and renal sodium excretion increase likely due to dobutamine-mediated decrease in renal and systemic reduced activation of sympathetic nervous- and renin–angiotensin–aldosterone system. Mechanical circulatory support with left ventricular assist devices ascertained the contribution of low cardiac output to diuretic resistance and the pathogenesis and progression of kidney disease in acutely decompensated heart failure. Summary Diuretic resistance commonly occurs in acutely decompensated heart failure. However, failure to resolve fluid overload despite high doses of loop diuretics should alert to the presence of a low cardiac output state.
 
Basic elements of the right ventricular pressure–volume loop. Two fundamental relationships create boundaries for the pressure–volume (PV) loop: the end-systolic PV relationship (ESPVR), which describes ventricular contractile properties, and the end-diastolic PV relationship (EDPVR), which describes ventricular diastolic function (A). ESPVR connects the ESPV coordinate with the volume-axis intercept (V0), or the unstressed blood volume of the ventricle. Afterload can be characterized by the effective arterial elastance (Ea), which connects the end-systolic coordinates and the V0 at end-diastolic volume (Ved, 0). The slope of the ESPVR is also known as end-systolic elastance (Ees) and is a measure of right ventricular (RV) contractility. The ratio of Ees to Ea represents an index of RV-pulmonary arterial (PA) coupling, which reflects the efficiency of energy transfer from the RV to the PA (B). The PV loop also provides a basis for better understanding myocardial energetics. The space within the loop is stroke work (SW), and the potential space bound within the ESPVR and the EDPVR, but outside the loop, is the potential energy (PE). The sum of SW and PE is the PV area (PVA), which correlates with total mechanical energy generated by ventricular contraction and is linearly related to myocardial oxygen consumption (C)
Pressure volume loops reflecting various mechanisms of right ventricular failure. The pressure volume (PV) loop of the volume overloaded right ventricle (RV) resembles that of the normal RV, but is rightward shifted along the end-diastolic PV relationship (EDPVR), reflecting increased RV end-diastolic volume and pressure (A). The PV loop of the pressure overloaded RV more closely resembles that of the left ventricle, with a higher effective arterial elastance (Ea) slope, reflecting higher afterload (B). The hypocontractile RV has a lower end-systolic PV relationship (ESPVR) slope (known as end-systolic elastance or Ees), reflecting loss of contractility (C)
Pressure volume loops reflecting the hemodynamic impact of various forms of right-sided mechanical circulatory support. Right atrial (RA) to pulmonary artery (PA) bypass (e.g., Impella RP, Protek Duo) leads to reduction in right-ventricular end-diastolic pressure and volume (RVEDP and RVEDV), with concomitant increase in right ventricular (RV) afterload (A–C). RV to PA bypass (e.g., CentriMag, Spectrum Medical dual lumen cannula) leads to more effective RV unloading with further reduction in RV end-systolic volumes (D–F). RA to aorta (Ao) bypass (e.g., peripheral VA ECMO) leads to reduction in RVEDP without a concomitant increase in RV afterload, assuming normal left ventricular function (G–I). EDPVR, the end-diastolic PV relationship; ESPVR, the end-systolic PV relationship
Pressure volume loops reflecting the impact of tricuspid regurgitation on the supported right heart. Tricuspid regurgitation (TR) in the presence of a right ventricular (RV) bypass device can serve to further unload the failing RV and decrease total RV afterload. RVF, right ventricular failure; RA, right atrium, PA, pulmonary artery, EDPVR, the end-diastolic PV relationship; ESPVR, the end-systolic PV relationship
Purpose of Review Right ventricular (RV) failure is increasingly recognized as a major cause of morbidity and mortality. When RV failure is refractory to medical therapy, escalation to right-sided mechanical circulatory support (MCS) should be considered. In this review, we begin by recapitulating the hemodynamics of RV failure, then we delve into current and future right-sided MCS devices and describe their hemodynamic profiles. Recent Findings The field of temporary right-sided MCS continues to expand, with evolving strategies and new devices actively under development. All right-sided MCS devices bypass the RV, with each bypass configuration conferring a unique hemodynamic profile. Devices that aspirate blood directly from the RV, as opposed to the RA or the IVC, have more favorable hemodynamics and more effective RV unloading. There has been a growing interest in single-access MCS devices which do not restrict patient mobility. Additionally, a first-of-its-kind percutaneous, pulsatile, right-sided MCS device (PERKAT RV) is currently undergoing investigation in humans. Summary Prompt recognition of refractory RV failure and deployment of right-sided MCS can improve outcomes. The field of right-sided MCS is rapidly evolving, with ongoing efforts dedicated towards developing novel temporary devices that are single access, allow for patient mobility, and directly unload the RV, as well as more durable devices.
 
Putative mechanisms directly linking HF to CD
Taken from Huynh QL et al., Eur J Heart Fail 2021 (reprinted with permission…). Demonstrating the impact of cognitive function on postdischarge outcomes in heart failure patients receiving a comprehensive discharge management plan
Management strategies and future direction for optimising care for heart failure patients with cognitive dysfunction. MoCA – Montreal Cognitive Assessment; CRT – cardiac resynchronization therapy; PMVR – percutaneous mitral valve repair; CD – cognitive dysfunction; HF – heart failure
Purpose of Review There is increasing recognition of the prevalence and impact of cognitive dysfunction (CD) in heart failure (HF) patients. This contemporary review appraises the evidence for epidemiological association, direct pathophysiological links and emerging pharmacological and non-pharmacological interventions. Furthermore, we present evidence for care models that aim to mitigate the morbidity and poor quality of life associated with these dual processes and propose future work to improve outcomes. Recent Findings CD disproportionately affects heart failure patients, even accounting for known comorbid risk factors, and this may extend to subclinical left ventricular dysfunction. Neuroimaging studies now provide evidence of anatomical and functional differences which support previously postulated mechanisms of reduced cerebral blood flow, micro-embolism and systemic inflammation. Interventions such as multidisciplinary ambulatory HF care, education and memory training improve HF outcomes perhaps to a greater degree in those with comorbid CD. Additionally, optimisation of standard heart failure care (cardiac rehabilitation, pharmacological and device therapy) may lead to additional cognitive benefits. Summary Epidemiological, neuroimaging and intervention studies provide evidence for the causal association between HF and CD, although evidence for Alzheimer’s dementia is less certain. Specific reporting of cognitive outcomes in HF trials and evaluation of targeted interventions is required to further guide care provision.
 
Cumulative probability of Chagas-related heart failure mortality
H&E stain, high power magnification showing parasite amastigotes (arrow), and associated myocarditis
Factors involved in diagnosis and treatment of Chagas disease during reinfections
Purpose of the Review Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections’ role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. Recent Findings Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host’s immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5 years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Summary Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.
 
Reducing complications surrounding device implantation
of assessment and management of device-related infections.
Adapted from Blomstom-Lundquist et al. [18]
Purpose of Review Cardiac implantable electronic device implant numbers are continually increasing due to the expanding indications and ageing population. This review explores the complications associated with device therapy and discusses ways to minimise and manage such complications. Recent Findings Complications related to device therapy contribute to mortality and morbidity. Recent publications have detailed clear guidelines for appropriate cardiac device selection, as well as consensus documents discussing care quality and optimal implantation techniques. There have also been advances in device technologies that may offer alternative options to patients at high risk of/or already having encountered a complication. Summary Adherence to guidelines, appropriate training, and selection of device, in addition to good surgical technique are key in reducing the burden of complications and improving acceptability of device therapy.
 
Purpose of Review Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role. Recent Findings Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain. Summary Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis.
 
Biomarkers for myocarditis. Graphics created with BioRender.com
Purpose of Review Myocarditis is a disease caused by inflammation of the heart that can progress to dilated cardiomyopathy, heart failure, and eventually death in many patients. Several etiologies are implicated in the development of myocarditis including autoimmune, drug-induced, infectious, and others. All causes lead to inflammation which causes damage to the myocardium followed by remodeling and fibrosis. This review aims to summarize recent findings in biomarkers for myocarditis and highlight the most promising candidates. Recent Findings Current methods of diagnosing myocarditis, including imaging and endomyocardial biopsy, are invasive, expensive, and often not done early enough to affect progression. Research is being done to find biomarkers of myocarditis that are cost-effective, accurate, and prognostically informative. These biomarkers would allow for earlier screening for myocarditis, as well as earlier treatment, and a better understanding of the disease course for specific patients. Summary Early diagnosis of myocarditis with biomarkers may allow for prompt treatment to improve outcomes in patients.
 
Suggested management algorithm for patients presenting with sK⁺  ≥ 5.5 mmol/L. ECG = electrocardiogram. IV = intravenous. RAASi = renin–angiotensin–aldosterone system inhibitor. sK⁺  = serum K⁺. SZC = sodium zirconium cyclosilicate. TDS = three times a day
Purpose of Review Heart failure (HF), in conjunction with common comorbidities such as chronic kidney disease and diabetes and medical therapies such as RAASi, predisposes to hyperkalaemia which may lead to hospitalisation and death. This paper aims to review the most current evidence surrounding the risks and management of hyperkalaemia in HF, with particular focus on recent research into RAASi including novel selective mineralocorticoid receptor blockers and novel potassium binders. Recent Findings The most recent evidence shows that even moderate hyperkalaemia may predispose to adverse outcomes such as hospitalisation and death. Furthermore, it may prevent patients from receiving optimal medical therapy for HF by reducing prescription of RAASi therapy. Novel potassium binders such as sodium zirconium cyclosilicate (SZC) and patiromer present potential options to reduce and prevent hyperkalaemia as well as maintain optimal RAASi dosing in HF. Summary Management of hyperkalaemia in HF has advanced in recent years. New therapies such as SZC and patiromer are contributing to the management of acute hyperkalaemia and also access to life-saving RAASi therapies by tackling and preventing hyperkalaemia in the community.
 
Hallmarks of PLN R14del. Five hallmarks of PLN R14del that have been identified on a cardiomyocyte level. A Contractile dysfunction, B Ca²⁺ dysregulation, C metabolic dysfunction, D protein aggregation, and E increased UPR activity. Created with BioRender.com
Modalities of precision medicine. Six modalities in precision medicine to be used for the treatment of genetic heart disease. Created with BioRender.com
A workflow for precision medicine in genetic heart disease. A workflow based on deep phenotyping of patient-derived material and in vitro disease modeling. This will allow identification of therapeutic targets and disease modifiers, which will be used for the identification of novel biomarkers and the development of precision medicine. These biomarkers will allow accurate disease monitoring and precision medicine will allow the development of novel treatment strategies that taken together will ultimately help in optimizing patient care. Created with BioRender.com
Purpose of Review Heart failure is a syndrome with poor prognosis and no curative options for the majority of patients. The standard one-size-fits-all-treatment approach, targeting neurohormonal dysregulations, helps to modulate symptoms of heart failure, but fails to address the cause of the problem. Precision medicine aims to go beyond symptom modulation and targets pathophysiological mechanisms that underlie disease. In this review, an overview of how precision medicine can be approached as a treatment strategy for genetic heart disease will be discussed. PLN R14del, a genetic mutation known to cause cardiomyopathy, will be used as an example to describe the potential and pitfalls of precision medicine. Recent Findings PLN R14del is characterized by several disease hallmarks including calcium dysregulation, metabolic dysfunction, and protein aggregation. The identification of disease-related biological pathways and the effective targeting using several modalities, including gene silencing and signal transduction modulation, may eventually provide novel treatments for genetic heart disease. Summary We propose a workflow on how to approach precision medicine in heart disease. This workflow focuses on deep phenotyping of patient derived material, including in vitro disease modeling. This will allow identification of therapeutic targets and disease modifiers, to be used for the identification of novel biomarkers and the development of precision medicine approaches for genetic cardiomyopathies.
 
Linear pathway of diagnosis of heart failure
Pathways for mild symptoms and the eventual diagnosis of heart failure
Pathways for severe symptoms and the eventual diagnosis of heart failure
Missed opportunities are incidents where different actions by those involved could have resulted in more desirable events. Heart failure is a complex clinical syndrome presenting as symptoms and signs common to other diagnoses, in patients frequently with multiple co-morbidities. Heart failure itself is not a diagnosis, but is the common clinical presentation of a variety of cardiac conditions. Correct diagnosis involves amalgamation of the clinical presentation, the results of general and specific investigations, and the clinician’s ability to synthesize the overall picture. It is not surprising therefore that misdiagnosis can occur at any level of the heart failure journey and can occur because of patient, clinician, and health economy related factors. Delayed diagnosis leads to excess morbidity and mortality in these patients. In this review, we define the pathways for diagnosis of heart failure and then highlight missed opportunities related to delay and misdiagnosis. In addition, we consider how the earlier opportunity may impact patients, clinicians and health services.
 
Schematic overview of sex hormone synthesis and cellular effects. In both men and women, cholesterol is the steroidogenic substrate for progesterone production in the adrenal gland. Besides being a functional hormone itself, progesterone is converted to testosterone in the ovaries of women (left) and in the testes of men (right). Subsequently, testosterone is converted to estradiol in the ovaries before being secreted into the circulation. Other organs—like the liver—produce estriol from estradiol. In men, testosterone is also converted to the more potent dihydrotestosterone in the testes. Once sex hormones (yellow) reach the target cells in the heart, they may induce downstream targets by direct or indirect genomic pathways via gene expression, or by interacting with a membrane-bound receptor and other effector proteins in various organelles
Purpose of Review Sex hormones drive development and function of reproductive organs or the development of secondary sex characteristics but their effects on the cardiovascular system are poorly understood. In this review, we identify the gaps in our understanding of the interaction between sex hormones and the cardiovascular system. Recent Findings Studies are progressively elucidating molecular functions of sex hormones in specific cell types in parallel with the initiation of crucial large randomized controlled trials aimed at improving therapies for cardiovascular diseases (CVDs) associated with aberrant levels of sex hormones. Summary In contrast with historical assumptions, we now understand that men and women show different symptoms and progression of CVDs. Abnormal levels of sex hormones pose an independent risk for CVD, which is apparent in conditions like Klinefelter syndrome, androgen insensitivity syndrome, and menopause. Moreover, sex hormone–based therapies remain understudied and may not be beneficial for cardiovascular health.
 
Purpose Kidney disease is a common finding in patients with heart failure and can significantly impact treatment decisions and outcomes. Abnormal kidney function is currently determined in clinical practice using filtration markers in the blood to estimate glomerular filtration rate, but the manifestations of kidney disease in the setting of heart failure are much more complex than this. In this manuscript, we review novel biomarkers that may provide a more well-rounded assessment of kidney disease in patients with heart failure. Recent Findings Galectin-3, ST2, FGF-23, suPAR, miRNA, GDF-15, and NAG may be prognostic of kidney disease progression. L-FABP and suPAR may help predict acute kidney injury (AKI). ST2 and NAG may be helpful in diuretic resistance. Summary Several biomarkers may be useful in determining prognosis of long-term kidney disease progression, prediction of AKI, and development of diuretic resistance. Further research into the mechanisms of kidney disease in heart failure utilizing many of these biomarkers may lead to the identification of therapeutic targets.
 
AlloMap genomic biomarker story. A Phases of development for the AlloMap gene expression profiling test using samples from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) study. B Accepted phases of development for biomarker tests in general [35]. EMB, endomyocardial biopsy; PCR, polymerase chain reaction. All images reproduced with permission
AlloMap scores depending on type of infection. Median and range of AlloMap gene expression profiling (GEP) scores depending on type of infection drawn within 30 days of infection. Median GEP score in this study cohort was 28 (IQR 22–33.5). Dotted red line denotes the threshold of rejection of 34 [36]. All images reproduced with permission
Multivariable immunological risk score for infection after transplant. Proposed application of a 5-variable immunological risk score to guide duration of antimicrobial prophylaxis after transplant. A score > 13 predicted heart transplant recipients to be at highest risk for infection (HR 9.29, p < 0.0001) 44•. C3, complement factor 3; NK, natural killer cells; CD4, T cell subset lymphocytes; IgG, immunoglobulin G; C4, complement factor 4; CMV, cytomegalovirus. All images reproduced with permission
Proposed algorithm for combined biomarker testing at all phases of transplant. Suggested algorithm to incorporate candidate biomarkers at key time points throughout all phases of transplant. Rejection surveillance should also be performed routinely
Purpose of Review Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population. Recent Findings While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Summary Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.
 
a Coronary CTA demonstrating noncalcified plaque (arrow). b Coronary CTA demonstrating calcified plaque (arrow). c Coronary CTA demonstrating coronary artery stent (arrow)
Volume rendering image of aorta and coronary tree with stents (arrows)
a Left ventricular apical infarct without perfusion imaging showing hypoattenuated infarcted area (arrow). b Left ventricular apical infarct with perfusion imaging illustrating infarcted area (arrow)
Left atrial appendage thrombus on cardiac CTA (arrow)
a Illustration of normal tricuspid aortic valve (arrow). b Illustration of calcified aortic valve (arrow)
Purpose of Review Cardiac computed tomography (CT) is becoming a more widely applied tool in the diagnosis and management of a variety of cardiovascular conditions, including heart failure. The aim of this narrative review is to examine the role of cardiac CT in patients with heart failure. Recent Findings Coronary computed tomographic angiography has robust diagnostic accuracy for ruling out coronary artery disease. These data are reflected in updated guidelines from major cardiology organizations. New roles for cardiac CT in myocardial imaging, perfusion scanning, and periprocedural planning, execution, and monitoring are being implemented. Summary Cardiac CT is useful in ruling out coronary artery disease its diagnostic accuracy, accessibility, and safety. It is also intricately linked to invasive cardiac procedures that patients with heart failure routinely undergo.
 
Metabolic modulation in heart failure. Reduction of fatty acid oxidation (FAO) can be achieved by decreasing circulating fatty acid levels (with the use peroxisome proliferator–activated receptor (PPAR) agonists and β-adrenoceptor antagonists), decreasing mitochondrial uptake of fatty acid (with the use of carnitine palmitoyl transferase 1 (CPT1) inhibitors etomoxir and perhexiline), or inhibiting FAO directly (with the use of trimetazidine). Stimulating glucose uptake and/or oxidation can be done by increasing glucose uptake (with the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) or increasing glucose oxidation (with the use of dichloroacetate that increases pyruvate dehydrogenase (PDH) complex activity by inhibiting PDK4). Ketone oxidation can be augmented by increasing ketone availability with the use of sodium-glucose co-transporter 2 (SGLT2 inhibitors) and ketone supplementation (e.g., ketone salts, ketone ester). CD36, fatty acid translocase (FAT); GLUT4, glucose transporters 4; MCT1, monocarboxylate transporter 1; BDH, beta-hydroxybutyrate dehydrogenase; SCOT, succinyl-CoA:3-ketoacid-CoA transferase; ATP, adenosine triphosphate; TCA, tricarboxylic acid; ETC, electron transport chain. Part of the illustrations elements courtesy of Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0
Purpose of Review We review the clinical benefits of altering myocardial substrate metabolism in heart failure. Recent Findings Modulation of cardiac substrates (fatty acid, glucose, or ketone metabolism) offers a wide range of therapeutic possibilities which may be applicable to heart failure. Augmenting ketone oxidation seems to offer great promise as a new therapeutic modality in heart failure. Summary The heart has long been recognized as metabolic omnivore, meaning it can utilize a variety of energy substrates to maintain adequate ATP production. The adult heart uses fatty acid as a major fuel source, but it can also derive energy from other substrates including glucose and ketone, and to some extent pyruvate, lactate, and amino acids. However, cardiomyocytes of the failing heart endure remarkable metabolic remodeling including a shift in substrate utilization and reduced ATP production, which account for cardiac remodeling and dysfunction. Research to understand the implication of myocardial metabolic perturbation in heart failure has grown in recent years, and this has raised interest in targeting myocardial substrate metabolism for heart failure therapy. Due to the interdependency between different pathways, the main therapeutic metabolic approaches include inhibiting fatty acid uptake/fatty acid oxidation, reducing circulating fatty acid levels, increasing glucose oxidation, and augmenting ketone oxidation.
 
Purpose of Review Small non-coding RNAs regulate gene expression and are highly implicated in heart failure. Recently, an additional level of post-transcriptional regulation has been identified, referred to as the epitranscriptome, which encompasses the body of post-transcriptional modifications that are placed on RNA molecules. In this review, we summarize the current knowledge on the small non-coding RNA epitranscriptome in heart failure. Recent Findings With the rise of new methods to study RNA modifications, epitranscriptome research has begun to take flight. Over the past 3 years, the number of publications on the epitranscriptome in heart failure has significantly increased, and we expect many more highly relevant publications to come out over the next few years. Summary Currently, at least six modifications on small non-coding RNAs have been investigated in heart failure-relevant studies, namely N6-adenosine, N5-cytosine and N7-guanosine methylation, 2’-O-ribose-methylation, adenosine-to-inosine editing, and isomiRs. Their potential role in heart failure is discussed.
 
Diversity of heart failure immunopathogenesis: infection, auto-inflammation, and impaired injury responses
Purpose of review: The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. Recent findings: HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.
 
Important considerations when assessing the appropriateness of individual medications and multi-drug regimens. This proposed framework helps change the narrative of polypharmacy to a nuanced analysis with the goal of optimizing medication regimens for an individual
Preliminary data from the FDA showing there is adequate clinical trial representation of adults with HF age 40–79 from 2010 to 2020 [40]. There is a relative scarcity of data for those ≥ 80 years old, despite high prevalence of disease in this population
Ecosystem of medical and social considerations and resources that need to be coordinated to provide healthcare for older adults with HF and optimize polypharmacy. A multidisciplinary clinic can serve as a medical home for complex patients and their caregivers, navigating these various resources and recommendations
Geriatrics deprescribing protocol [87] modified to include a final step of re-prescribing medications if and when appropriate
Different layers of health and well-being all specialists (including cardiologists and HF specialists) may be able to assess, integrate, and optimize for older adults with HF and polypharmacy
Purpose of Review We provide a review of considerations when applying principles of optimal pharmacotherapy to older adults with heart failure (HF), an analysis on the pivotal clinical trials focusing on applicability to older adults, and multi-disciplinary strategies to optimize the health of HF patients with polypharmacy. Recent Findings Polypharmacy is very common among patients with HF, due to medications for both HF and non-HF comorbidities. Definitions of polypharmacy were not developed specifically for older adults with HF and may need to be modified in order to meaningfully describe medication burden and promote appropriate medical therapy. This is because clinical practice guidelines for multi-drug HF regimens have unique considerations, given that they improve outcomes and symptoms of HF. Summary Adults older than 65 years are well represented in contemporary clinical trials for HF with preserved ejection fraction (HFpEF) and guideline directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). While these trials did not have significant heterogeneity in safety or efficacy across a broad age spectrum, some may have limited representation of adults ≥ 80 years old, the sickest older adults, or those with decreased functional status. There is also a lack of data on the safety and efficacy of deprescribing HF medications, and deprescription in otherwise stable patients may lead to clinical destabilization or disease progression. There is therefore innate tension between the well-studied benefits of optimized HF therapy for older adults that must be weighed against the risks of polypharmacy and many unknowns that still exist. Given the strong evidence that optimized HF therapies confer symptomatic and mortality benefits for older adults, it is clear that polypharmacy in this context can be appropriate. A shift in paradigm is therefore needed when evaluating polypharmacy in patients with HF. Instead of assuming all polypharmacy is “good” or “bad,” we propose a concerted move, using a multidisciplinary approach, to focus on the “appropriateness” of specific medications, in order to optimize HF medical therapy. Clinicians of all specialties caring for complex older adults with HF must consider goals of care, functional status, and new evidence-based therapies, in order to optimize this polypharmacy for older adults.
 
Varying imaging modalities and causes of heart failure in women. TTE, (transthoracic echocardiogram) — images A–C. Patient with non-ischaemic cardiomyopathy. Apical 4-chamber view in diastole (A) and systole (B) showing severely impaired systolic function (LVEF 20%) by Simpson’s Biplane. Strain map showing globally reduced longitudinal strain (C). CCT, cardiovascular computed tomography — images D–G. Coronary artery calcium scoring (D), curved reformats showing mixed calcified and non-calcified atheroma (E) and calcified plaque (F), and short axis cine (G). CMR, cardiovascular magnetic resonance — images H–K. 4ch cine of dilated heart (H), subendocardial infarct on LGE images (I), mid-wall inflammation of myocarditis seen on T1 map (J), global subendocardial perfusion defect on short axis perfusion map (K). PET, positron emission tomography — images L–N. Focal intense FDG uptake in the left ventricle (D–E) and affecting the basal inferoseptum, inferior, inferolateral, and lateral walls (E). Axial slice showing FDG avidity in the mediastinal lymph nodes (F) in a patient with a history of systemic and cardiac sarcoidosis
Purpose of Review To summarise the role of different imaging techniques for diagnosis and investigation of heart failure in women. Recent Findings Although sex differences in heart failure are well recognised, and the scope of imaging techniques is expanding, there are currently no specific guidelines for imaging of heart failure in women. Summary Diagnosis and stratification of heart failure is generally performed first line using transthoracic echocardiography. Understanding the aetiology of heart failure is central to ongoing management, and with non-ischaemic causes more common in women, a multimodality approach is generally required using advanced imaging techniques including cardiovascular magnetic resonance imaging, nuclear imaging techniques, and cardiac computed tomography. There are specific considerations for imaging in women including radiation risks and challenges during pregnancy, highlighting the clear unmet need for cardiology and imaging societies to provide imaging guidelines specifically for women with heart failure.
 
The contrast between the traditional model of heart failure care (left), with a modern digitally-supported patient-centric model of heart failure care (right). The traditional model uses fixed periodic review with a healthcare organisation (HCO) focus on reactive management of patient crises. The modern model of heart failure care uses digital technology to support patients at various stages of their heart failure illness, allowing dynamic management of issues as they arise. Healthcare organisation focus is on pro-active health maintenance. HCP, healthcare professional; HCO, healthcare organisation; CIEDs, cardiac implantable electronic devices; Apps, smartphone applications
What are remote monitoring and remote patient management?
Key elements to consider for successful remote patient management. Modified with permission from Angermann C, 2019 [59]. AI, artificial intelligence; HCP, healthcare professional
The range of digital technologies that patients with heart failure potentially have available to them
Purpose of Review In this article, we review a range of digital technologies for possible application in heart failure patients, with a focus on lessons learned. We also discuss a future model of heart failure management, as digital technologies continue to become part of standard care. Recent Findings Digital technologies are increasingly used by healthcare professionals and those living with heart failure to support more personalised and timely shared decision-making, earlier identification of problems, and an improved experience of care. The COVID-19 pandemic has accelerated the acceptability and implementation of a range of digital technologies, including remote monitoring and health tracking, mobile health (wearable technology and smartphone-based applications), and the use of machine learning to augment data interpretation and decision-making. Much has been learned over recent decades on the challenges and opportunities of technology development, including how best to evaluate the impact of digital health interventions on health and healthcare, the human factors involved in implementation and how best to integrate dataflows into the clinical pathway. Summary Supporting patients with heart failure as well as healthcare professionals (both with a broad range of health and digital literacy skills) is crucial to success. Access to digital technologies and the internet remains a challenge for some patients. The aim should be to identify the right technology for the right patient at the right time, in a process of co-design and co-implementation with patients.
 
Overview of the metabolic-inflammatory circuit in HFpEF. Metabolic comorbidities elicit a chronic proinflammatory state that evokes microvascular and myocardial dysfunction. The release of proinflammatory mediators can promote oxidative stress that subsequently impedes endothelial and cardiomyocyte function. Targeting myocardial inflammation and oxidative stress may help to restore nitric oxide bioavailability, the latter being critical for endothelial-cardiomyocyte crosstalk
Molecular mechanisms underlying the metabolic-inflammatory circuit. Systemic and local inflammation evoke an inflammation-oxidative stress feedback loop in cardiomyocytes that activates signalling networks for cardiac hypertrophy and fibrosis which induce contractile dysfunction. Anti-hypertensive agents and SGLT2 inhibitors may indirectly suppress this loop and attenuate the HFpEF phenotype
Classification of HFpEF phenogroups. Distinct phenogroups have been identified within the collective HFpEF subgroup. The potential disparity in molecular signatures between each phenogroup raises the need for phenogroup-specific interventions
Purpose of Review Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality. The current mechanistic paradigm supports a comorbidity-driven systemic proinflammatory state that evokes microvascular and myocardial dysfunction. Crucially, diabetes and obesity are frequently prevalent in HFpEF patients; as such, we review the involvement of a metabolic-inflammatory circuit in disease pathogenesis. Recent Findings Experimental models of diastolic dysfunction and genuine models of HFpEF have facilitated discovery of underlying drivers of HFpEF, where metabolic derangement and systemic inflammation appear to be central components of disease pathophysiology. Despite a shared phenotype among these models, molecular signatures differ depending on type and combination of comorbidities present. Summary Inflammation, oxidative stress, hypertension, and metabolic derangements have been positioned as therapeutic targets to suppress the metabolic-inflammatory circuit in HFpEF. However, the stratification of unique patient phenogroups within the collective HFpEF subgroup argues for specific interventions for distinct phenogroups.
 
Pathophysiological interactions between AF and HF. Atrial fibrillation (AF) and heart failure (HF) commonly co-exist, with interacting causal mechanisms driving the occurrence of each condition. Shared risk factors include advanced age, hypertension, diabetes, obesity, sleep apnea, and chronic kidney disease. Legend: atrial fibrillation (AF); atrioventircular (AV); heart failure (HF); pulmonary vein (PV)
Treatment options for patients with concomitant AF and HF. The approach to managing atrial fibrillation (AF) and heart failure (HF) includes management of precipitants and co-morbid risk conditions, stroke prevention therapies, and optimization of goal-directed heart failure therapies. The rhythm management in an HF patient depends on the prevention (acute vs. chronic), the specific arrhythmia (atrial flutter vs. fibrillation), and the clinical categorization (paroxysmal vs. persistent vs. permanent). In general, sinus rhythm maintenance is preferred in newly diagnosed AF, and symptomatic patients with HF. When sinus rhythm is desired catheter ablation to achieve pulmonary vein isolation (PVI) is the preferred therapeutic strategy, being strongly preferred in those with tachycardia-induced cardiomyopathy and in those where antiarrhythmic drugs have failed. Atrioventricular junction (AVJ) ablation is a reasonable strategy for those with a pre-existing biventricular pacemaker-defibrillator or in those with permanent AF when heart rate (HR) cannot be controlled. Legend: AF, atrial fibrillation; AFL, atrial flutter; CV, cardioversion; DCCV, electrical cardioversion; LVEF, left ventricular ejection fraction; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; ND-CCB, non-dihydropyridine calcium channel blocker; OAC, oral anticoagulation
Purpose of Review Atrial fibrillation (AF) and heart failure (HF) are commonly encountered clinical disorders that often co-exist, accelerating disease progression and adverse outcomes. It is known that restoration of sinus rhythm positively impacts this population; however, the complex comorbidity profile associated with HF introduces intricacies not encountered in other patient populations. The current review focuses on the safety and efficacy of an interventional-based management for atrial tachyarrhythmias in HF. Recent Findings While pharmacotherapy has been the standard treatment of cardiac dysrhythmias in the HF population, recent evidence suggests catheter ablation is more effective and causes less harm than antiarrhythmic drugs (AADs) in the HF population. Summary For the maintenance of sinus rhythm, catheter ablation results in improved freedom from recurrent arrhythmia, with secondary benefit on mortality and hospitalization in those with HF and reduced ejection fraction. For those with permanent AF, cardiac resynchronization therapy and atrioventricular junction ablation result in improved quality of life, physical functioning, and cardiac function.
 
PRISMA flow chart of the article selection process
Bubble chart depicting correlations between MUGA and other imaging modalities. Most represent the Pearson correlation coefficient, while some studies reported Lin’s concordance (asterisk) or a correlation coefficient from linear regression analysis (dagger). The bubbles represent the correlation between the mentioned tests and MUGA over time, while factoring in the number of participants included (bubble size). 2DF two-dimensional fundamental echocardiography (red), 2DH two-dimensional harmonic echocardiography (orange), 2DHC two-dimensional harmonic echocardiography with contrast (brown), 3D three-dimensional echocardiography (blue), A angiography (yellow), CMR cardiac magnetic resonance imaging (green), and TD thermodilution (purple)
Overview of Bland-Altman 95% limits of agreement. Mean bias is depicted as a black horizontal stripe, the 95% LOA by the colored bars, and the predefined clinical acceptable limit of 10% left ventricular ejection fraction (LVEF) differences by the horizontal lines at ±10% LVEF. 2DF two-dimensional fundamental echocardiography (red), 2DH two-dimensional harmonic echocardiography (orange), 2DHC two-dimensional harmonic echocardiography with contrast (brown), 3D three-dimensional echocardiography (blue), A angiography (yellow), and CMR cardiac magnetic resonance imaging (green)
Central illustration: flow diagram of proposed imaging strategy for patients at risk for cancer therapy-related cardiac dysfunction. Preferred modality ranges from top to bottom, from most to least preferred. 2D two-dimensional, 3D three-dimensional, and MUGA multigated acquisition scan. *LVEF obtained by MUGA after CMR monitoring should be interpreted cautiously, since these modalities show poor agreement with one another
Purpose of Review The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably. Recent Findings In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Summary Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.
 
Evaluation and management of HF defined by ACC/AHA guidelines: evolution and recommended therapy by HF stage. Adapted from Hunt [50]. ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; EF, ejection fraction; FHx CM, family history of cardiomyopathy; HF, heart failure; LV, left ventricular LVH, left ventricular hypertrophy; MI, myocardial infarction
PRISMA flow chart of searches on the epidemiology of stage B HF, as defined by ACC/AHA guidelines
Purpose of Review To quantify the prevalence of asymptomatic pre-heart failure (pre-HF), progression to more severe stages, and associated mortality. Recent Findings A systematic review was conducted between 01 January 2010 and 12 March 2020 (PROSPERO: CRD42020176141). Data of interest included prevalence, disease progression, and mortality rates. In total, 1030 sources were identified, of which, 12 reported on pre-HF (using the ACC/AHA definition for stage B HF) and were eligible. Prevalence estimates of pre-HF ranged from 11 to 42.7% (10 sources) with higher estimates found in the elderly, in patients with hypertension, and in men. Three studies reported on disease progression with follow-up ranging from 13 months to 7 years. The incidence of symptomatic HF (HF/advanced HF) ranged from 0.63 to 9.8%, and all-cause mortality from 1.6 to 5.4%. Summary Further research is required to investigate whether early detection and intervention can slow or stop the progression from asymptomatic to symptomatic HF.
 
NAD⁺ redox balance, consumption and synthesis. Redox turnover of NAD⁺ is essential for substrate catabolism, e.g. glycolysis (green). NAD⁺ is consumed as a substrate by Sirtuins, Parps and NAD⁺ hydrolases, yielding NAM and an ADPR moiety. These NAD⁺-consuming enzymes regulate PTMs of proteins, NAD⁺ levels and cellular functions. NAD⁺ is synthesized through three pathways—the de novo pathway (blue), the Preiss-Handler Pathway (yellow) and the salvage pathway (orange). De novo NAD⁺ synthesis starts with IDO, mediating the rate-limiting step with the conversion of tryptophan to N-formylkin. After several enzymatic reactions, the intermediate, ACMS, undergoes spontaneous cyclization to form QA, which is the second rate-limiting step. ACMS can be further metabolized to AMS by ACMSD and enter TCA cycle. Inhibition of ACMSD is reported to elevate NAD⁺ levels by directing ACMS to NAD⁺ synthesis via QA. QA is converted to NAMN by QPRT using PRPP as a co-substrate. In the Preiss-Handler pathway, NA is metabolized to NAMN by NAPRT. The de novo and Preiss-Handler pathways converge at NAMN, which is further metabolized into NAAD by NMNATs at the expense of ATP. NAD⁺ is synthesized from NAAD under the catalysis of NADS. NAM from NAD⁺ consumption and NR from diet serve as NAD⁺ precursors for the salvage pathway, in which NAM and NR are converted into a common product, NMN, by NAMPT or NMRK, respectively. NMN is converted into NAD⁺ by NMNAT, the same enzymes used in the Preiss-Handler pathways. Abbreviations: poly-ADP-ribose polymerases (Parps), nicotinamide phosphoribosyltransferase (Nampt), nicotinamide mononucleotide adenylyl transferases (Nmnats), NA phosphoribosyltransferase (Naprt), nicotinamide riboside kinases (Nmrks), quinolinic acid phosphoribosyltransferase (Qprt), indoleamine 2,3-dioxygenase (Ido), tryptophan 2,3-dioxygenase (Tdo), kynurenine monooxygenase (Kmo), kynureninase (Kynu), 3-hydroxyanthranilate-3,4-dioxygenase (Haao), ACMS decarboxylase (Acmsd), tryptophan (TRP), N-formylkynurenine (N-formylkin), L-kinurenine (L-KIN), 3-hydroxyanthranilate (3-HAA), α-amino-β-carboxymuconate-semialdehyde (ACMS), α-aminomuconate-semialdehyde (AMS), adenosine diphosphate ribose (ADPR), quinolinic acid (QA), nicotinic acid (NA), nicotinic acid mononucleotides (NAMN), nicotinic acid adenine dinucleotide (NAAD), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), post-translational modifications (PTMs)
Impacts of cardiometabolic diseases and pharmacologic interventions on NAD⁺ homeostasis. Cardiometabolic diseases are associated with NAD⁺ depletion. These stresses differentially impact NAD⁺ salvage pathway, which is the dominant synthesis pathway in the hearts. Failing hearts and diabetes promote NAD⁺ redox imbalance (low NAD⁺/NADH ratio), while failing hearts are also associated with lowered NAMPT expression. Failing hearts have up-regulated Nmrk2 expression, whose role in the pathogenesis is obscure. Pharmacologic agents to enhance NAD⁺ synthesis or to inhibit consumption increase cellular NAD⁺ levels. Boosting NAD⁺ levels via precursors such as NR and NMN, or NAMPT activation improves cardiac outcomes. Alternatively, inhibitions of PARPs (by INO1001, ABT-888) and CD38 (by 78c) demonstrate therapeutic effects
Purpose of the Review This review summarizes current understanding on the roles of nicotinamide adenine dinucleotide (NAD+) metabolism in the pathogeneses and treatment development of metabolic and cardiac diseases. Recent Findings NAD+ was identified as a redox cofactor in metabolism and a co-substrate for a wide range of NAD+-dependent enzymes. NAD+ redox imbalance and depletion are associated with many pathologies where metabolism plays a key role, for example cardiometabolic diseases. This review is to delineate the current knowledge about harnessing NAD+ metabolism as potential therapy for cardiometabolic diseases. The review has summarized how NAD+ redox imbalance and depletion contribute to the pathogeneses of cardiometabolic diseases. Therapeutic evidence involving activation of NAD+ synthesis in pre-clinical and clinical studies was discussed. Summary While activation of NAD+ synthesis shows great promise for therapy, the field of NAD+ metabolism is rapidly evolving. Therefore, it is expected that new mechanisms will be discovered as therapeutic targets for cardiometabolic diseases.
 
The role of matrix metallopeptidases in myocytes
Purpose of Review This review highlights the key studies investigating various types of biomarkers in Duchenne muscular dystrophy (DMD). Recent Findings Several proteomic and metabolomic studies have been undertaken in both human DMD patients and animal models of DMD that have identified potential biomarkers in DMD. Summary Although there have been a number of proteomic and metabolomic studies that have identified various potential biomarkers in DMD, more definitive studies still need to be undertaken in DMD patients to firmly correlate these biomarkers with diagnosis, disease progression, and monitoring the effects of novel treatment strategies being developed.
 
Drugs targeting mechano-energetic uncoupling in heart failure. In the normal heart, calcium (Ca²⁺) accumulation in the mitochondrial matrix stimulates the regeneration of reducing equivalents required for both adenosine triphosphate (ATP) production and hydrogen peroxide (H2O2) elimination. In the failing heart, decreased Ca²⁺ release from the sarcoplasmic reticulum and elevated cytosolic sodium (Na⁺) hinder mitochondrial Ca²⁺ accumulation, causing bioenergetic mismatch and oxidative stress. Drugs lowering cytosolic Na⁺ or inhibiting Ca²⁺ extrusion from mitochondria via the mitochondrial Na⁺/Ca²⁺ exchanger (NCLX) might ameliorate cardiac function by restoring mechano-energetic coupling. Other abbreviations: ADP, adenosine diphosphate; GSH/GSSG, reduced/oxidized form of glutathione; IMM, inner mitochondrial membrane; late INa, late sodium current; MCU, mitochondrial Ca²⁺ uniporter; Mn-SOD, manganese-dependent superoxide dismutase; NAD⁺/NADH, oxidized/reduced form of nicotinamide dinucleotide; NCX, sarcolemmal Na⁺/Ca²⁺ exchanger; NKA, Na⁺/K⁺ ATPase; NNT, nicotinamide nucleotide transhydrogenase; OMM, outer mitochondrial membrane; RyR2, ryanodine receptor type 2; SERCA, SR Ca²⁺ ATPase; SGLT2i, Na⁺/glucose cotransporter 2 inhibitors; TRXr/TRXo, reduced/oxidized form of thioredoxin
Drugs targeting substrate preference in heart failure. The normal heart relies primarily on glucose and fatty acid oxidation for adenosine triphosphate (ATP) production. Emerging evidence indicates that in the failing heart, oxidation of ketones such as β-hydroxybutyrate (β-OHB) might become a relevant
source of ATP. Because ATP production from glucose or β-OHB oxidation requires less oxygen than fatty acid oxidation, a metabolic shift away from fatty acids toward glucose and/or ketone oxidation for ATP production increases cardiac efficiency. Inhibition of fatty acid β-oxidation can be achieved by (i) inhibiting carnitine palmitoyltransferase 1 (CPT1), which mediates fatty acid import in the mitochondrial matrix, with etomoxir; (ii) directly inhibiting β-oxidation with trimetazidine; (iii) increasing malonyl-CoA levels by inhibiting its degradation with malonyl-CoA decarboxylase (MCD) inhibitors. Furthermore, the hyperketonemic state associated with sodium/glucose cotransporter 2 inhibitors (SGLT2i) treatment may provide cardiac myocytes with a more energetically efficient substrate, i.e., β-OHB. Other abbreviations: ACC, acetyl-CoA carboxylase; ADP, adenosine diphosphate; ETC, electron transport chain; FAT/CD36, fatty acid translocase; GLUT1/4, glucose transporter 1/4; MCT, monocarboxylate transporter; NAD⁺/NADH, oxidized/reduced form of nicotinamide dinucleotide; PDH, pyruvate dehydrogenase
Purpose of Review We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production. Recent Findings Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes. Summary The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.
 
Schematization of the different pathological conditions that may lead to heart failure
Evolution of artificial intelligence and its main components, in which deep learning represents a subset of machine learning methods
Purpose of Review Application of deep learning (DL) is growing in the last years, especially in the healthcare domain. This review presents the current state of DL techniques applied to electronic health record structured data, physiological signals, and imaging modalities for the management of heart failure (HF), focusing in particular on diagnosis, prognosis, and re-hospitalization risk, to explore the level of maturity of DL in this field. Recent Findings DL allows a better integration of different data sources to distillate more accurate outcomes in HF patients, thus resulting in better performance when compared to conventional evaluation methods. While applications in image and signal processing for HF diagnosis have reached very high performance, the application of DL to electronic health records and its multisource data for prediction could still be improved, despite the already promising results. Summary Embracing the current big data era, DL can improve performance compared to conventional techniques and machine learning approaches. DL algorithms have potential to provide more efficient care and improve outcomes of HF patients, although further investigations are needed to overcome current limitations, including results generalizability and transparency and explicability of the evidences supporting the process.
 
Purpose of the Review We aimed to provide an overview of telemedical monitoring and its impact on outcomes among heart failure (HF) patients. Recent Findings Most HF readmissions may be prevented if clinical parameters are strictly controlled via telemedical monitoring. Predictive algorithms for patients with cardiovascular implantable electronic devices (e.g., Triage-HF Plus by Medtronic or HeartLogic by Boston Scientific) were developed to identify patients at significantly increased risk of HF events. However, randomized control trial-based data are heterogeneous regarding the advantages of telemedical monitoring in HF patients. The likelihood of adverse clinical outcomes increases when pulmonary artery pressure (PAP) rises, usually days to weeks before clinical manifestations of HF. A wireless monitoring system (CardioMEMS™) detecting changes in PAP was proposed for HF patients. CardioMEMS™ transmits data to the healthcare provider and allows to institute timely intensification of HF therapies. CardioMEMS™-guided pharmacotherapy reduced a risk of HF-related hospitalization (hazard ratio [HR]: 0.72; 95% confidence interval (CI) 0.60–0–0.85; p < 0.01). Summary Relevant developments and innovations of telemedical care may improve clinical outcomes among HF patients. The use of CardioMEMS™ was found to be safe and cost-effective by reducing the rates of HF hospitalizations.
 
Person-centered care of the cardio-oncology patient from diagnosis to death
Purpose of Review The current review describes the role of the cardio-oncology nurse and the need for personalized heart failure care for the patient with cancer. Recent Findings It is a new role whereby cardiology or heart failure nurses care for patients with cancer who develop cardiotoxicity or cardiovascular diseases, either during the cancer therapy or in a later stage. Inter-disciplinary approach is important for individualized early treatment, shortened interruptions to cancer therapy, and irreversible cardiovascular injury prevention. Nurses have a key role in early evaluation and quality control of the care provided. Summary This is a quite new clinical area and not much evidence exists for the development of clinical guidelines and pathways to support clinicians. More trials are needed for the development of clinical recommendations.
 
Mechanism of action for loop diuretics
With a spot urine sample obtained 2 h after loop diuretic administration, the 6-h cumulative total sodium output and urinary output can be predicted accurately [13]
Purpose of Review Loop diuretics are the cornerstone of the treatment of congestion in heart failure patients. The manuscript aims to summarize the most updated information regarding the use of loop diuretics in heart failure. Recent Findings Diuretic response can be highly variable between patients and needs to be carefully evaluated during and after the hospitalization. Diuretic resistance can lead to residual congestion which affects prognosis and can be difficult to detect. The effect of loop diuretics on long-term prognosis remains uncertain but patients with advanced heart failure typically have renal dysfunction and are more inclined to develop loop diuretic resistance, which may lead to an incomplete decongestion and thus to a worse prognosis. Summary Loop diuretics are the most potent diuretics available and their use is recommended in order to alleviate symptoms, improve exercise capacity, and reduce hospitalizations in patients with heart failure. Their use should be limited to the lowest dose necessary to maintain euvolemia because a low dose does not increase the risk of decompensation but reduce the risk of adverse effects and allow the up-titration of disease-modifying drugs.
 
Physiological changes during pregnancy
Purpose of the Review The purpose of this review is to discuss the risk stratification and management of pregnancy in women with complex congenital heart disease. Recent Findings Classifying congenital heart defects (CHD) including both anatomy and physiology is important for maternal risk stratification. Although most women with CHD can tolerate the physiological challenge of pregnancy, some may experience serious risks both to their health and that of their foetus. The WHO maternal risk classification model remains the best-validated risk measure. Ideally, women with CHD should have pre-conception assessment with a CHD cardiologist. General principles of management, such as need for expert centre delivery, a multidisciplinary team, epidural and mode of delivery are based on WHO risk in combination with expert assessment of status. Summary CHD is increasingly prevalent in women of child-bearing age. Assessment by an adult CHD cardiologist, ideally pre-conception, is key in assessing and minimising risk to mother and foetus.
 
Heart failure with reduced ejection fraction-does sex matter? The impact of sex in HFrEF can be demonstrated through the mechanisms and demographics, presenting features and outcomes. Where men are more likely to develop HFrEF from ischaemic heart disease (IHD), present with lower ejection fractions and have a higher mortality, women tend to have non-ischaemic cardiomyopathy or valvu-
Heart failure with reduced ejection fraction—does sex matter? The impact of sex in HFrEF can be demonstrated through the mechanisms and demographics, presenting features and outcomes. Where men are more likely to develop HFrEF from ischaemic heart disease (IHD), present with lower ejection fractions and have a higher mortality, women tend to have non-ischaemic cardiomyopathy or valvular aetiology of HFrEF, be older at presentation, are more likely to have comorbidities like hypertension and chronic kidney disease, and experience more symptoms and report a poorer quality of life. QOL, quality of life; LOS, length of stay; HFrecEF, heart failure with recovered ejection fraction; IHD, ischaemic heart disease; LVEF, left ventricular ejection fraction
Purpose of Review There is an increasing recognition of the importance of sex in susceptibility, clinical presentation, and outcomes for heart failure. This review focusses on heart failure with reduced ejection fraction (HFrEF), unravelling differences in biology, clinical and demographic features and evidence for diagnostic and therapeutic strategies. This is intended to inform clinicians and researchers regarding state-of-the-art evidence relevant to women, as well as areas of unmet need. Recent Findings Females are well recognised to be under-represented in clinical trials, but there have been some improvements in recent years. Data from the last 5 years reaffirms that women presenting with HFrEF women are older and have more comorbidities like hypertension, diabetes and obesity compared with men and are less likely to have ischaemic heart disease. Non-ischaemic aetiologies are more likely to be the cause of HFrEF in women, and women are more often symptomatic. Whilst mortality is less than in their male counterparts, HFrEF is associated with a bigger impact on quality of life in females. The implications of this for improved prevention, treatment and outcomes are discussed. Summary This review reveals distinct sex differences in HFrEF pathophysiology, types of presentation, morbidity and mortality. In light of this, in order for future research and clinical medicine to be able to manage HFrEF adequately, there must be more representation of women in clinical trials as well as collaboration for the development of sex-specific management guidelines. Future research might also elucidate the biochemical foundation of the sex discrepancy in HFrEF.
 
A schematic diagram summarizing the pathophysiology and mechanisms of action for a broad range of breast cancer therapies that have been shown to cause cardiotoxicity. (Figure
adapted from Lenneman, C and Sawyer, D Circ Res.2016;118:1008–1020; Sayed et al.,Cardiovasc Res.2019;115(5):949–959)
The brief algorithm recommended for patients undergoing treatment with potentially cardiotoxic therapies. (Figure
adapted from Dobson, R et al. J Am Coll Cardiol CardioOnc. 2021;3(1):1–16)
Purpose of Review Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on ‘omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity.Recent FindingsSignificant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities.SummaryThere is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.
 
Top-cited authors
Rudolf Allert de Boer
  • University of Groningen
Sophie Van Linthout
  • Berlin Institute of Health
Carsten Tschöpe
  • Berlin Institute of Health ( BIH) at Charite
Sanjiv Shah
  • Northwestern University
P. Christian Schulze
  • Universitätsklinikum Jena