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Heart failure with preserved ejection fraction (HFpEF) is frequently observed in elderly physically deconditioned subjects, mainly women with hypertension, obesity, glucose intolerance/diabetes, atrial fibrillation, anaemia, coronary artery disease, chronic pulmonary disease, and chronic renal insufficiency. In practice, these conditions represent the majority of cardiac diseases we deal with in our daily clinical practice. For this reason, the HFpEF disease does not exist as a single entity and, as such, no specific unifying therapy could be found. New classification attempts still do not consider the multifaceted aspect of the HF syndrome and appear rather as an artefactual attempt to categorize a condition which is indeed not categorizable. The aim of the present article is to critically review the construction of the concept of the HFpEF syndrome and propose the return of a pathophysiological approach in the evaluation and treatment of patients. Considering the huge economic efforts employed up to date to run awfully expensive trials and research in this field, it is time to call action and redirect such resources towards more specific pathophysiological classifications and potential specific therapeutic targets.

With its high spatial resolution and tissue contrast, cardiac magnetic resonance (CMR) is an extremely flexible imaging technique that enables a thorough morphological and functional evaluation of the heart and vascular system. From diagnosis to treatment planning and risk assessment, CMR is being utilized more and more in the evaluation of patients with heart failure (HF). CMR offers a variety of techniques for characterizing myocardial tissue, aiding in identifying the cause of HF, as well as whole-heart cine imaging for precise measurement of biventricular dimensions and function. The aim of this review is to the describe the role of CMR in chronic heart failure, in particular for diagnostic workups, differential diagnosis, and information on how CMR influences treatment planning choices.

In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients.

In clinical practice, heart failure (HF) and osteoporosis (OP) are commonly paired conditions. This association is particularly relevant in patients over the age of 50, among whom its prevalence increases dramatically with every decade of life. This can be especially impactful since patient prognosis when facing both conditions is poorer than that of each disease alone. Clinical studies suggest that prior fractures increase the risk for heart failure hospitalization and, conversely, an episode of heart failure increases the risk of subsequent fractures. In other words, the relationship between osteoporosis and heart failure seems to be two-way, meaning that each condition may influence or contribute to the development of the other. However, the details of the pathophysiological relationship between HF and OP have yet to be revealed. The two conditions share multiple pathological mechanisms that seem to be intertwined. Patients affected by OP are more prone to develop HF because of vitamin D deficiency, elevation of parathyroid hormone (PTH) plasma levels, and increased Fibroblast Growth Factor 23 (FGF-23) activity. On the other hand, HF patients are more prone to develop OP and pathological fractures because of low vitamin D level, high PTH, chronic renal failure, alteration of renin–angiotensin–aldosterone system, reduced testosterone level, and metabolic effects derived from commonly used medications. Considering the increasingly aging worldwide population, clinicians can expect to see more often an overlap between these two conditions. Thus, it becomes crucial to recognize how HF and OP mutually influence the patient’s clinical condition. Clinicians attending these patients should utilize an integrated approach and, in order to improve prognosis, aim for early diagnosis and treatment initiation. The aim of this paper is to perform a review of the common pathophysiological mechanisms of OP and HF and identify potentially new treatment targets.

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function.

Alterations of cardiac metabolism can be present in several cardiac syndromes. Heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents, such as trimetazidine and perhexiline, that directly inhibit fatty acid oxidation. These agents have been originally adopted to increase the ischemic threshold in patients with effort angina. However, the results of current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with heart failure is reviewed and discussed.

31-Phosphorus-magnetic resonance spectroscopy may provide pathophysiological insights into the high-energy phosphate metabolism of the myocardium as measured by phosphocreatine to adenosine triphosphate (PCr/ATP) ratio. Aim of the present study was to determine in vivo the relation between cardiac PCr/ATP ratio and heart rate in normal male subjects. One hundred twelve apparently healthy, young male individuals (age 34 ± 10 years) were prospectively evaluated. They underwent cardiac cine magnetic resonance imaging to assess left ventricular (LV) function and morphology and 3D-ISIS 31P-magnetic resonance spectroscopy of the LV to assess the PCr/ATP ratio (a recognized in vivo marker of myocardial energy metabolism). Data were analyzed after segregation by tertiles of the resting PCr/ATP ratio. A significant inverse association between PCr/ATP ratios and resting heart rate was observed (Spearman ρ: r=−0.37; P < .0001). PCr/ATP ratios were also inversely associated with body mass index, diastolic blood pressure, wall mass and with insulin resistance, but in multiple regression analysis heart rate was found to be independently related to PCr/ATP. The present study shows that resting heart rate is proportionally lower across tertiles of increasing PCr/ATP ratio of the LV in apparently healthy young male individuals, supporting the hypothesis that heart rate is a major determinant of cardiac energy stores. These findings may explain the prognostic role of heart rate in the general population as evidenced by previous large epidemiological studies.