Moderate aortic stenosis in the dysfunctional ventricle: should it be treated?

Moderate aortic stenosis is associated with a worse prognosis than milder degrees. Pathophysiologically, this condition in a dysfunctional ventricle could lead to a further mechanism of haemodynamic worsening, so its treatment should lead to clinical advantages for the patient. The low risk of complications associated with percutaneous correction of aortic valve disease (transcatheter aortic valve implantation) should also be considered, which would seem to favour an interventional approach even in the aforementioned condition. However, sparse data and small population studies make this approach still controversial. Three randomized controlled trials are underway to shed definitive light on the topic.

Heart failure therapy: the fifth card.

The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and propose four drug classes (enzyme inhibitors conversion agents, angiotensin receptor antagonists, beta-blockers, and sodium-glucose cotransporter inhibitors 2) to be initiated and titrated in all patients with an ejection fraction <35%. This new approach offers advantages such as rapid introduction and titration, better tolerability, and early instrumental re-evaluation. In the VICTORIA study, the molecule vericiguat, a soluble guanylate cyclase activator, was shown to reduce the composite outcome of death from cardiovascular causes and first hospitalization for HF in a high-risk population. An additional randomized clinical trial (VICTOR) is ongoing to evaluate the efficacy and safety of vericiguat in a population with HF on optimized therapy and with no recent episodes of stabilization.

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Corrigendum to: In pursuit of balance: RAASi and hyperkalemia treatment.

[This corrects the article DOI: 10.1093/eurheartjsupp/suad053.].

Heart Failure Preserved Ejection Fraction in Women: Insights Learned from Imaging.

While the prevalence of heart failure, in general, is similar in men and women, women experience a higher rate of HFpEF compared to HFrEF. Cardiovascular risk factors, parity, estrogen levels, cardiac physiology, and altered response to the immune system may be at the root of this difference. Studies have found that in response to increasing age and hypertension, women experience more concentric left ventricle remodeling, more ventricular and arterial stiffness, and less ventricular dilation compared to men, which predisposes women to developing more diastolic dysfunction. A multi-modality imaging approach is recommended to identify patients with HFpEF. Particularly, appreciation of sex-based differences as described in this review is important in optimizing the evaluation and care of women with HFpEF.

Role of continuous glucose monitoring in diabetic patients at high cardiovascular risk: an expert-based multidisciplinary Delphi consensus.

BACKGROUND: Continuous glucose monitoring (CGM) shows in more detail the glycaemic pattern of diabetic subjects and provides several new parameters ("glucometrics") to assess patients' glycaemia and consensually guide treatment. A better control of glucose levels might result in improvement of clinical outcome and reduce disease complications. This study aimed to gather an expert consensus on the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk or with heart disease. METHODS: A list of 22 statements concerning type of patients who can benefit from CGM, prognostic impact of CGM in diabetic patients with heart disease, CGM use during acute cardiovascular events and educational issues of CGM were developed. Using a two-round Delphi methodology, the survey was distributed online to 42 Italian experts (21 diabetologists and 21 cardiologists) who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. RESULTS: Forty experts (95%) answered the survey. Every statement achieved a positive consensus. In particular, the panel expressed the feeling that CGM can be prognostically relevant for every diabetic patient (70%) and that is clinically useful also in the management of those with type 2 diabetes not treated with insulin (87.5%). The assessment of time in range (TIR), glycaemic variability (GV) and hypoglycaemic/hyperglycaemic episodes were considered relevant in the management of diabetic patients with heart disease (92.5% for TIR, 95% for GV, 97.5% for time spent in hypoglycaemia) and can improve the prognosis of those with ischaemic heart disease (100% for hypoglycaemia, 90% for hyperglycaemia) or with heart failure (87.5% for hypoglycaemia, 85% for TIR, 87.5% for GV). The experts retained that CGM can be used and can impact the short- and long-term prognosis during an acute cardiovascular event. Lastly, CGM has a recognized educational role for diabetic subjects. CONCLUSIONS: According to this Delphi consensus, the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk is promising and deserves dedicated studies to confirm the experts' feelings.

Ventricular-arterial coupling in systemic lupus erythematosus women without cardiovascular risk factors.

Systemic lupus erythematosus (SLE) is characterized by endothelial dysfunction, arterial stiffness, and myocardial impairment. We aimed at analyzing the ratio between carotid-femoral pulse wave velocity (cfPWV) and left ventricular global longitudinal strain (GLS) as a new index to approximate ventricular-arterial coupling (VAC) in women with SLE and without cardiovascular risk factors. Half cases had impaired GLS and consequently a hampered ratio. We thus suggest referring SLE patients early to a CV prevention program.

Empagliflozin in heart failure with preserved ejection fraction: first success in mission impossible.

Heart failure and preserved ejection fraction (EF) is a common disease with a poor prognosis and increasing prevalence in the community. The current treatment paradigm includes symptomatic therapy, such as diuretics, risk factor control, and treatment of comorbidities. According to the most recent European guidelines, there is no effective therapy in patients with heart failure and left ventricular EF ≥50%, while the pharmacological compounds normally used in heart failure with reduced EF could also be implemented in patients with EF slightly reduced (between 40 and 50%), with a recommendation class IIB. The recently published Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) study challenged current guidelines, showing for the first time in patients with heart failure and EF >40% better outcomes with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin than with placebo. This result was consistent in patients with and without diabetes, as well as in those with EF below and above 50%. The purpose of the review is to describe the rationale for this important finding and the main results of the EMPEROR-Preserved study and to provide some suggestions for the daily clinical management of SGLT2 inhibitors.

Essential Hypertension and Oxidative Stress: Novel Future Perspectives.

Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.

Coeliac and cardiovascular disease: a possible relationship between two apparently separate conditions.

Coeliac disease (CD) is an autoimmune condition with a high prevalence among general population and multisystemic involvement: a more complex scene than a merely gastrointestinal disease. Therefore, an early diagnosis and treatment with a gluten-free diet is mainly important to reduce mortality and comorbidities. Together with autoimmune diseases (as Hashimoto thyroiditis, insulin-dependent diabetes mellitus, autoimmune liver disease and connective tissue diseases), also an accelerated progression of atherosclerosis and a higher prevalence of heart disease have been reported in coeliacs. In the present paper we tried to collect from literature the emergent data on the probable relationship between coeliac and cardiovascular disease, focusing on pathophysiological bases of vascular injury. Data and opinions on the development of cardiovascular risk in patients with CD are conflicting. However, the major evidence supports the theory of an increased cardiovascular risk in CD, due to many mechanisms of myocardial injury, such as chronic malabsorption, abnormalities of intestinal permeability, and direct immune response against self-proteins. The conclusions that come from these data suggest the utility of a careful cardiovascular follow up in coeliac patients.

Indirect comparison between ferric carboxymaltose and oral iron replacement in heart failure with reduced ejection fraction: a network meta-analysis.

Treatment of iron deficiency (ID) in patients with heart failure (HF) has improved symptoms, quality of life, exercise capacity and has reduced hospitalizations in randomized controlled trials (RCTs) and meta-analyses. Intravenous ferric carboxymaltose (FCM) provided convincing results in this field, while oral iron supplementation failed. However, FCM and oral iron were compared to placebo, and a comparison between the two strategies is still lacking. We aimed to fill this gap of knowledge with an indirect comparison between them by means of a network meta-analysis of RCTs. Five studies measuring exercise capacity (i.e. 6-minute walking test) and quality of life (i.e. Kansas City Cardiomyopathy Questionnaire) were eligible to be included in our review. Given the limitations of a network meta-analysis, our findings support the better efficacy of FCM than oral iron as regards exercise capacity, with a trend towards an improvement in quality of life, suggesting that FCM seems to be strategy of choice to correct ID in HF patients.

Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus-A New Indication? A Meta-summary of Case Reports.

Left ventricular thrombus (LVT) can be a consequence of cardiac diseases such as heart failure with reduced ejection fraction and acute myocardial infarction. Currently, the guidelines recommend the use of warfarin for the treatment of this condition. However, there are increasing reports of patients with LVTs being treated with direct oral anticoagulants (DOACs), for several reasons. We set out to review the available literature to assess the safety and the efficacy of this approach. We analyzed 52 cases, extrapolated by 34 papers contained in literature, focusing on the characteristics of patients, treatment, outcome, and follow-up. Rivaroxaban was the most commonly used DOAC, followed by apixaban. The diagnosis of LVT and the follow-up were mainly performed by transthoracic echocardiography. The thrombus resolved in 45 patients (92%) of 49 (there are no data available regarding the outcome of 3 patients) and failed to resolve in 4 patients treated with DOACs. The resolution occurred in a median of 32 days. DOACs are shown to be a reasonable and valid option for the treatment of LVT. Our study provides a rationale for a prospective randomized controlled trial.

The brain-heart connection: a multiple sclerosis relapse presenting as Takotsubo Syndrome. A case report and literature review.

We hereby report a puzzling case of multiple sclerosis (MS) relapse presenting as Takotsubo syndrome (TTS). Female, 42-years old, who presented herself to the Emergency Room of University Hospital "ASST Spedali Civili" of Brescia, Italy, for a severe headache and a non-ST-segment elevation acute coronary syndrome. Coronary angiogram showed no signs of coronary atherosclerosis. Upon further neurological evaluation, a diagnosis of MS relapse, related to TTS, was made, and treatment was started accordingly. The patient was discharged after 12 days after the admission, free of symptoms, and without signs of neurological and cardiological active disease. A hallmark of TTS is its association with a preceding stressful event. It may also be connected to a wide variety of diseases, including neurological ones, such as stroke, intracranial bleeding, head trauma, migraine, and seizures. However, up to our knowledge, only few cases of MS-induced TTS were previously described. Whether it is plausible to consider TTS as an uncommon extra-neurological manifestation of MS is still debated, however all the evidence points in that direction, considering the central role of catecholamines in TTS pathogenesis. With this case report the authors hope to encourage research on this field and on the intricate topic of brain-heart connections.

Elastic aortic properties in cystic fibrosis adults without cardiovascular risk factors: A case-control study.

INTRODUCTION: The presence of CFTR in smooth muscle and endothelial cells, systemic inflammation, and oxidative stress could explain vascular alterations in cystic fibrosis. Aortic elastic properties are determinants of left ventricular function by means of ventriculo-arterial coupling and indicators of cardiovascular risk. OBJECTIVES: The purpose of the present study was to compare clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate aortic tissue Doppler elastic properties, such as distensibility, stiffness, and strain. METHODS: A total of 22 adults affected by cystic fibrosis, and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors, secondary diabetes, neither aortic stenosis nor regurgitation. All people underwent blood pressure measurement and transthoracic echocardiography. RESULTS: Aortic diameter measured at Valsalva sinuses was significantly higher in patients with cystic fibrosis than healthy people, median 32.0 (interquartile range 29.8-35.0) vs 24.3 (22.2-30.0) mm; P < 0.001. Aortic distensibility was significantly lower among patients than controls, being 2.4 (1.3-3.3) vs 5.6 (3.4-8.3) per mm Hg (P < 0.001), while stiffness higher, 7.7 (6.0-14.8) vs 3.7 (2.9-6.7); P < 0.001. Finally, M-mode strain of ascending aorta was lower in patients, 4.1 (3.4-7.3)% than in controls, 13.4 (7.7-19.4)%; P < 0.001. CONCLUSION: For the first time in humans, we demonstrated subclinical alterations in aortic elastic properties in young adults affected by cystic fibrosis without pulmonary hypertension or secondary diabetes. This phenomenon could influence left ventricular function earlier by means of ventriculo-arterial coupling and may be a tool to identify patients who benefit from a closer follow-up.

The Effect of Chorionicity on Maternal Cardiac Adaptation to Uncomplicated Twin Pregnancy: A Prospective Longitudinal Study.

OBJECTIVE: The objective of this study was to longitudinally evaluate maternal echocardiographic findings in uncomplicated twin gestations according to chorionicity. METHODS: Healthy women with twin pregnancy were assessed with transthoracic echocardiography across the first, second, and third trimesters. Cardiac findings were compared within each group and between monochorionic (MC) and dicho-rionic (DC) pregnancies. RESULTS: Overall, 19 MC and 48 DC uncomplicated twin pregnancies were included. In the MC group, no significant maternal haemodynamic changes were documented across gestation, with the exception of a decrease in ejection fraction. Compared to DC pregnancies, in the MC set lower cardiac output (second and third trimester, p = 0.001 and p = 0.006, respectively) and higher total vascular resistance (first trimester, p = 0.032) were observed. Regarding the diastolic function in MC twins, significantly higher values were observed for mitral E/A ratio (third trimester, p = 0.014), septal mitral E1/A1 ratio (third trimester, p = 0.030), lateral mitral E1 (second and third trimester, p = 0.014 and p = 0.029, respectively), and E1/A1 ratio (third trimester, p = 0.006). CONCLUSIONS: Maternal cardiac adaptation in twin pregnancy seems to differ significantly according to chorionicity. In particular, in MC pregnancies the impairment of diastolic function is less pronounced, presumably due to the lower circulating volume.

The role of heart rate and ivabradine in acute heart failure.

Resting heart rate (HR) is considered a powerful predictor of mortality both in healthy subjects and in cardiovascular (CV) patients, including those affected by heart failure (HF). Its reduction below 70 bpm is the treatment target in chronic HF with reduced ejection fraction (HFrEF) when sinus rhythm is present. In acute HF (AHF) HR is usually elevated but its role as risk marker is still unknown. Notably, in unstable patients, beta-blockers can be reduced or stopped, thus enhancing this phenomenon. Moreover, some data in literature suggest that HR reduction during hospitalization or HR at discharge or in the vulnerable phase after it are more predictive of early-term events and may be therapeutic targets. On the other hand, ivabradine is a pure HR-lowering drug with no effects on inotropism. Its role in the AHF setting has been recently investigated and is the object of this review.

Wellens' syndrome: a case report with atypical features.

Wellens' syndrome is a pattern of electrocardiographic T-wave changes seen in the precordial leads in patients with unstable angina. Two different patterns have been described. Type A presents with biphasic T-waves in V2-V3 and type B presents with symmetrical deep T-wave inversions in V2-V3. The etiology is related to a critical stenosis in the proximal left anterior descending artery (LAD). We describe a patient who presented at our emergency department with intermittent chest pain and showing Wellens' pattern T-wave inversions in the precordial leads of the electrocardiogram. She was found to have 95% stenosis in mid LAD.

Macro- and microvascular functions in cystic fibrosis adults without cardiovascular risk factors: A case-control study.

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself.

Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy.

BACKGROUND: Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), as it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by nonischaemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up. MATERIALS AND METHODS: A total of 202 patients affected by nonischaemic DCM underwent an outpatient examination by echocardiography and blood pressure check at the brachial artery, in order to calculate aortic elastic properties (ie, compliance, distensibility, stiffness index, Peterson's elastic modulus, M-mode strain). ROC curves, Kaplan-Meier curves and multivariable Cox regressions (correcting for age, LV ejection fraction (LVEF), atrial fibrillation, cardiac resynchronization therapy (CRT)) were run to assess the predictive ability of aortic elastic properties against the 3 end-points. RESULTS: Mean follow-up was 9.83 ± 2.80 years. 24.8% of patients died, while 34.7% were rehospitalized for HF cause and 44.6% experienced the combined end-point. LVEF did not correlate with aortic elastic properties. ROC curves and Kaplan-Meier curves were elaborated. Aortic stiffness did not predict death in our cohort. Otherwise, all aortic elastic properties predicted HF rehospitalization and combined death or HF rehospitalization, after correcting for age, LVEF, atrial fibrillation, CRT. CONCLUSIONS: Elastic properties of the ascending aorta measured by echocardiography in patients with nonischaemic DCM predict long-term HF rehospitalization and combined death or HF rehospitalization, also after correcting for the confounding factors.

The role of type 2 diabetes mellitus on hypertensive-related aortic stiffness.

BACKGROUND: Hypertension is strongly related to arterial stiffness in a cause-effect fashion. Diabetes mellitus is also thought to determine vascular damage, mostly by means of advanced glycosylation end-products (AGEs). Aim of our study was to study the role of type 2 diabetes mellitus (T2DM) as regard ascending aortic elastic properties in hypertensive patients. METHODS: We prospectively enrolled outpatients with hypertension (n = 99) and type 2 diabetes mellitus plus hypertension (n = 42) without cardiovascular events. They underwent a transthoracic echocardiography to measure aortic diameters, aortic elastic properties (ie, compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse wave velocity, M-mode strain), tissue Doppler imaging (TDI) to calculate diastolic (E' and A') and systolic (S') velocities, and tissue strain. Multivariable analysis was run to assess the association between T2DM and these variables after correcting for possible confounders (age, sex, body mass index [BMI], dyslipidemia). RESULTS: The two groups did not differ as regards age, sex, BMI, and blood pressure. However, T2DM patients were more likely to be dyslipidemic (43% vs 71%, P = .003). Aortic diameters were similar in the two groups, but the aortic elastic properties significantly more impaired in T2DM group. At multivariable analysis, stiffness index, Peterson's elastic modulus, the TDI waves, and the tissue strain remained associated with the co-presence of T2DM and hypertension. CONCLUSION: Our data suggest that people suffering from both T2DM and hypertension have more impaired aortic elastic properties than those hypertensive alone. Considering the prognostic role of aortic stiffness, these patients may benefit from a closer follow-up.