Javier Díez

There is strong evidence that hypertension is a major risk factor for heart failure (HF). Hypertension contributes to incident HF through direct and indirect effects. Indirect effects are consequences of ischaemic heart disease because hypertension facilitates atherosclerotic obstructive coronary artery disease. The direct effects are straightly related to hypertensive heart disease (HHD). Hypertensive heart disease poses a significant challenge with substantial medical and public health implications. Efforts should be made to recognize and manage HHD in a timely manner and optimize hypertension treatment. Reducing blood pressure (BP) and/or reassessing antihypertensive therapy using traditional or novel approaches can halt or delay progression to HF in patients with HHD and possibly prevent it. However, HHD’s importance as a risk factor for overt HF is often overlooked in clinical practice. This document aims to summarize the current understanding of the burden of HHD and its risk for incident HF, discuss the mechanisms underlying HHD-related HF onset and progression, consider how diagnostic tools contribute to individualized phenotyping and HF risk stratification of HHD, address how therapeutic measures ameliorating or even preventing structural and functional alterations of HHD, along with BP control influence HHD-associated HF risk.

Aims: To evaluate whether circulating N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) can stage hypertensive heart disease (HHD), by assessing their association with adverse cardiac remodelling and cardiovascular outcomes in individuals with essential hypertension. Methods and Results: The REMODEL study prospectively enrolled 1054 asymptomatic individuals with essential hypertension and no prior cardiovascular diseases (59 ± 11 years old; systolic blood pressure 131 ± 14 mmHg; left ventricular ejection fraction 60 ± 7%). All participants underwent cardiovascular magnetic resonance (CMR) and blood sampling for NT-proBNP and hsTnT. The primary outcome was a composite of acute coronary syndromes, heart failure hospitalization, stroke and all-cause mortality. Median follow-up was 53 (23, 72) months. Maximal log-rank statistic identified thresholds of 152 pg/ml for NT-proBNP and 12.7 pg/ml for hsTnT. Individuals with elevations in both biomarkers (high-risk) were older, had the highest 24-h systolic blood pressure and more diabetes mellitus. They showed the most adverse CMR phenotype, with increased myocardial mass, greater diffuse and replacement fibrosis, impaired left ventricular strain and higher left atrial volumes. Event rates differed significantly across biomarker strata (log-rank P < .001). High-risk individuals had the greatest hazard of cardiovascular events [hazard ratio (HR) 17.11; 95% confidence interval (CI) 8.12–36.09), while intermediate-risk individuals showed intermediate risk (HR 3.44; 95% CI 1.71–6.94). Conclusion: NT-proBNP and hsTnT are complementary biomarkers that not only predict cardiovascular outcomes and but also reflect the severity of cardiac remodelling in HHD. Their combined use enables effective staging of disease severity and may support stage-specific management strategies in patients with hypertension.

Background: Chronic kidney disease (CKD) is associated with a markedly increased risk of cardiovascular disease (CVD). Despite this, cardiovascular risk in patients with CKD is frequently underestimated and insufficiently treated in routine clinical practice. Summary: In this narrative review, we address ten concise and up-to-date questions focused on cardiovascular risk management in CKD. A panel of ten expert nephrologists provides evidence-based perspectives on key aspects including assessment of the arterial tree, cardiovascular risk estimation, identification of biomarkers for improved risk stratification, and both pharmacological and non-pharmacological interventions proven to reduce cardiovascular risk. Additional topics include blood pressure targets, optimal management of dyslipidemia, and cardiovascular risk management in patients receiving renal replacement therapy. Practical strategies to translate this evidence into everyday clinical care are also discussed. Key Message: A comprehensive and structured approach to cardiovascular risk assessment and management are essential in patients with CKD and should be systematically integrated into routine nephrology practice to improve cardiovascular outcomes.

Myokines are signalling moieties released by the skeletal muscle in response to acute and/or chronic exercise, which exert their beneficial or detrimental effects through paracrine and/or autocrine pathways on the skeletal muscle and through endocrine pathways in many other organs (e.g. the heart). Interestingly, alterations in myokines have been described in patients with heart failure (HF) that are associated with adverse structural and functional left ventricular remodelling and poor cardiac outcomes. Recent experimental and clinical studies have shown that the muscle regulation of a number of myokines is altered in chronic kidney disease (CKD) thus representing a new molecular aspect of the pathophysiology of skeletal myopathy present in patients with CKD. Muscle dysregulation of myokines may contribute to a number of disorders in non-dialysis and dialysis patients with CKD, including the high risk of developing HF. This possibility would translate into a range of new diagnostic and therapeutic options. In fact, the measurement of circulating myokines opens their possible usefulness as biomarkers to personalize exercise training and pharmacological therapies for the prevention and treatment of HF in patients with CKD and skeletal myopathy. This review will analyse information on some myokines that target the heart and are altered at the level of skeletal muscle and circulation in patients with CKD.

Epidemiological studies have revealed that hypertensive heart disease is a major risk factor for heart failure, and its heart failure burden is growing rapidly. The need to act in the face of this threat requires first an understanding of the multifactorial origin of hypertensive heart disease and second an exploration of new mechanistic pathways involved in myocardial alterations critically involved in cardiac dysfunction and failure (eg, myocardial interstitial fibrosis). Increasing evidence shows that alterations of gut microbiota composition and function (ie, dysbiosis) leading to changes in microbiota-derived metabolites and impairment of the gut barrier and immune functions may be involved in blood pressure elevation and hypertensive organ damage. In this review, we highlight recent advances in the potential contribution of gut microbiota alterations to myocardial interstitial fibrosis in hypertensive heart disease through blood pressure–dependent and blood pressure–independent mechanisms. Achievements in this field should open a new path for more comprehensive treatment of myocardial interstitial fibrosis in hypertensive heart disease and, thus, for the prevention of heart failure.

Introduction. Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. Methods. The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Results. Among 5012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. Conclusions. Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Hypertensive heart disease (HHD) can no longer be considered as the beneficial adaptive result of the hypertrophy of cardiomyocytes in response to pressure overload leading to the development of left ventricular hypertrophy. The current evidence indicates that in patients with HHD, pathological lesions in the myocardium lead to maladaptive structural remodeling and subsequent alterations in cardiac function, electrical activity, and perfusion, all contributing to poor outcomes. Diffuse myocardial interstitial fibrosis is probably the most critically involved lesion in these disorders. Therefore, in this review, we will focus on the histological characteristics, the mechanisms, and the clinical consequences of myocardial interstitial fibrosis in patients with HHD. In addition, we will consider the most useful tools for the noninvasive diagnosis of myocardial interstitial fibrosis in patients with HHD, as well as the most effective available therapeutic strategies to prevent its development or facilitate its regression in this patient population. Finally, we will issue a call to action for the need for more fundamental and clinical research on myocardial interstitial fibrosis in HHD.

There is an unmet need to create consensus documents on the management of cardiorenal patients since, due to the aging of the population and the rise of both pathologies, these patients are becoming more prevalent in daily clinical practice. Chronic kidney disease coexists in up to 40%–50% of patients with chronic heart failure cases. There have yet to be consensus documents on how to approach palliative care in cardiorenal patients. There are guidelines for patients with heart failure and chronic kidney disease separately, but they do not specifically address patients with concomitant heart failure and kidney disease. For this reason, our document includes experts from different specialties, who will not only address the justification of palliative care in cardiorenal patients but also how to identify this patient profile, the shared planning of their care, as well as knowledge of their trajectory and the palliative patient management both in the drugs that will help us control symptoms and in advanced measures. Dialysis and its different types will also be addressed, as palliative measures and when the decision to continue or not perform them could be considered. Finally, the psychosocial approach and adapted pharmacotherapy will be discussed.

The term ventricular remodelling refers to alterations in size, shape, and function due to the response of the ventricle to sustained stress. Initially, the remodelling response to pathological stress helps in compensating the cardiac performance, but over time the response becomes maladaptive and leads to ventricular dysfunction. Thus, adverse ventricular remodelling is critically involved in the development of heart failure and its poor clinical outcome. Depending on the underlying pathology, the ventricle can remodel either concentrically or eccentrically. At the myocardial level, the adverse remodelling process implies tissue alterations involving the cardiomyocyte, interstitium, and microcirculation, as well as metabolic and electrophysiological alterations. Multiple mechanisms participate in the development of these alterations, highlighting the complexity and heterogeneity of the remodelling process. Understanding these mechanisms is necessary for both preventing and effectively reversing ventricular remodelling with therapy in heart failure patients.

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5–8). Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = −0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = −0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002–1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.