Cardiac herniation: A practical review in the emergency setting.

INTRODUCTION: Albeit described since 1948, cardiac herniations still represent an under-recognized clinical entity in the general population, due to their difficult diagnostic detection and to a limited knowledge in clinical practice. This paper aims to provide an updated overview focusing on definition, clinical presentation and diagnostic work-up of cardiac herniations, as well as on further findings concerning prognoses and available therapeutic options. METHODS: This narrative review was performed by following the standard methods of the Cochrane Collaboration and the PRISMA statement. A Pubmed search was conducted using the following keywords (in Title and/or Abstract): ("cardiac" OR "heart") AND ("herniation" OR "hernia"). All available high quality resources containing information on epidemiology, etiopathogenesis, clinical findings, diagnostic tools and therapeutic strategies, were included in our search. RESULTS: Causative agents, location and the degree of haemodynamic impairment were found to play a pivotal role in defining the patient's natural history and prognostic outcomes, and in detecting potential associated clinical conditions which may significantly impact on first line decision-making strategy. CONCLUSIONS: Cardiac herniations remain a rare and life-threatening pathological injury, whose knowledge is still very limited in clinical practice. Clinicians should be aware of such a clinical entity and of its wide spectrum of clinical manifestations, particularly in high-risk subsets of patients, in order to provide the most appropriate decision-making strategy and timely therapeutic approach.

Atrial fibrillation and Alzheimer's disease: A conundrum.

During ageing, the prevalence of Alzheimer's disease (AD) and of cardiovascular disease CVD) increases. Our aim is to investigate the relationship between AD and CVD and its risk factors, with a view to explaining the underlying mechanisms of this association. This review is based on the material obtained via MEDLINE (PubMed), Embase and Clinical Trials databases, from January 1980 until May 2019. The search term used was "Alzheimer's disease", combined with "cardiovascular disease", "hypertension", "dyslipidaemia", "diabetes mellitus", "atrial fibrillation", "coronary artery disease", "heart valve disease", "heart failure". Out of the 1328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed; thus, only 98 papers were included in our research material. We have found that AD and CVD are frequently associated, while both of them, alone may be considered deleterious to health, the study of their combination constitutes a clinical challenge. Further research will help to clarify the real impact of CVD and its risk factors on AD, in order to better comprehend the effects of subclinical and clinical cardiovascular diseases on the brain. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being: hypoperfusion and emboli, atherosclerosis, furthermore in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. We need to clarify the real impact of these underlying hypothesized mechanisms and to investigate gender issues.

Echocardiography of right ventricular-arterial coupling predicts survival of elderly patients with heart failure and reduced to mid-range ejection fraction.

Echocardiography of right ventricular (RV)-arterial coupling obtained by the estimation of the ratio of the longitudinal annular systolic excursion of the tricuspid annular plane and pulmonary artery systolic pressure (TAPSE/PASP) has been found to be a remarkable prognostic indicator in patients with HF. Our aim was to evaluate the impact of TAPSE, PASP and their ratio in the prognostic stratification of outpatients with HF aged ≥70 years and reduced to mid-range ejection fraction (EF). A complete echocardiographic examination was performed in 400 outpatients with chronic HF and left ventricular (LV) EF ≤50% who averaged 77 years in age. During a median follow-up period of 25 months (interquartile range: 8-46), there were 135 cardiovascular deaths. Two different Cox regression models were evaluated, one including TAPSE and PASP, separately, and the other with TAPSE/PASP. In the first model, LV end-systolic volume index, age, no angiotensin converting enzyme (ACE) inhibitor use, TAPSE, PASP and gender were found to be independently associated with the outcome after adjustment for demographics, clinical, biochemical, echocardiographic data. In the second model, TAPSE/PASP resulted the most important independent predictor of outcome (hazard ratio [HR]:0.07, p<0.0001) followed by LV end-systolic volume index, no ACE inhibitor use, age and gender. The use of the variable TASPE/PASP improved the predictive value of the new multivariable model (area under the curve [AUC] of 0.74 vs AUC of 0.71; p<0.05). TASPE/PASP improved the net reclassification (NRI = 14.7%; p<0.01) and the integrated discrimination (IDI = 0.04; p<0.01). In conclusion, the study findings showed that assessment of RV-arterial coupling by TAPSE/PASP was of major importance to assess the prognosis of patients with chronic HF and LV EF ≤50% aged ≥70 years.

The Organ Handling of Soluble Klotho in Humans.

BACKGROUND: Chronic kidney disease (CKD) reduces both Klotho expression and its shedding into circulation, an effect that accelerates progression and cardiovascular complications. However, the mechanisms that regulate Klotho release by the human kidney are still unknown. METHODS: We measured plasma Klotho across the kidney, splanchnic organs and lung in 22 patients (71 ± 2 years, estimated glomerular filtration rate [eGFR] 60 ± 5.4 mL/min 1.73 m2) during elective diagnostic cardiac catheterizations. RESULTS: Although the Klotho average renal vein concentrations were remarkably higher (by ∼9%) than arterial values, the kidney removed Klotho (or was at zero balance) in 7 subjects, indicating that the kidney contribution to systemic Klotho is not constant. Klotho fractional enrichment across the kidney was inversely related to plasma sodium (r = 0.43, p = 0.045) and acid uric acid levels (r = 0.38, p = 0.084) and directly, to renal oxygen extraction (r = 0.56, p = 0.006). In multivariate analysis, renal oxygen extraction was the only predictor of the enrichment of Klotho across the kidney, suggesting the dependence of renal Klotho release on tubular hypoxia or oxidative metabolism. Klotho balance was neutral across the lung. In patients with eGFR <60 mL/min, Klotho was also removed by splanchnic organs (single pass fractional extraction ∼11%). CONCLUSIONS: The present study identifies kidney oxygen uptake as a predictor of Klotho release, and splanchnic organs as a site for Klotho removal. This study provides new understanding of kidney Klotho release and suggests that modulating kidney oxygen metabolism could increase Klotho delivery, as an option to slow disease progression and blunt organ damage.

Optimizing Management of Heart Failure by Using Echo and Natriuretic Peptides in the Outpatient Unit.

Chronic heart failure (HF) is an important public health problem and is associated with high morbidity, high mortality, and considerable healthcare costs. More than 90% of hospitalizations due to worsening HF result from elevations of left ventricular (LV) filling pressures and fluid overload, which are often accompanied by the increased synthesis and secretion of natriuretic peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a rise in NP circulating levels are well known indicators of poor prognosis. Frequent office visits with the resulting evaluation and management are most often needed. The growing pressure from hospital readmissions in HF patients is shifting the focus of interest from traditionally symptom-guided care to a more specific patient-centered follow-up care based on clinical findings, BNP and echo. Recent studies supported the value of serial NP measurements and Doppler echocardiographic biomarkers of elevated LV filling pressures as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of echo and pulsed-wave blood-flow and tissue Doppler with NPs appears valuable in guiding ambulatory HF management, since they are potentially useful to distinguish stable patients from those at high risk of decompensation.

Interorgan handling of fibroblast growth factor-23 in humans.

Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 ± 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ∼22%. The FE of FGF-23 across the kidney was similar to that of creatinine (∼17%, P = NS). In addition, the FGF-23 FE by the kidney was significantly directly related to eGFR (r = 0.709 P = 0.018) and to kidney creatinine FE (r = 0.736 P = 0.013) but only as a trend to plasma phosphate levels (r = 0.55, P = 0.18). There was no difference in FGF-23 levels in blood perfusing splanchnic organs and cardiopulmonary bed. However, the arterial-venous difference of FGF-23 across the lung was directly related to FGF-23 pulmonary artery levels, suggesting that the lung, and possibly the heart, participate in the homeostasis of plasma FGF-23 when its systemic levels are increased. Our data show that the human kidney is the only site for FGF-23 removal from blood and suggest that FGF-23 is predominantly removed by glomerular filtration. The kidney ability to remove FGF-23 from the circulation likely accounts for the early increase in blood of FGF-23 in patients with CKD.

Combining echo and natriuretic peptides to guide heart failure care in the outpatient setting: A position paper.

BACKGROUND: Chronic heart failure (HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources. METHODS: This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were as follows: "heart failure, echocardiography, natriuretic peptides" in combination with "treatment, biomarkers, guidelines." RESULTS: Recent studies have supported the value of natriuretic peptides (NPs) and Doppler echocardiographic biomarkers of increased left ventricular (LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, that is to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce rehospitalization. CONCLUSION: We discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF.

Update on cardiotoxicity of anti-cancer treatments.

BACKGROUND AND AIMS: Anti-cancer treatments markedly improved the prognosis of patients, but unfortunately might be hampered by cardiotoxicity. Both symptomatic and asymptomatic clinical forms of heart failure have been reported, which may be reversible or irreversible. The aim of this review is to provide an overview of the antineoplastic agents associated with cardiac toxicity and of the available diagnostic techniques. METHODS AND METHODS: This narrative review is based on material from MEDLINE and PUBMED up to November 2015. We looked at the terms antineoplastic drugs and cardiac toxicity in combination with echocardiography, troponins, cardiac magnetic resonance, and positron emission tomography. RESULTS: Anthracyclines, monoclonal antibodies, fluoropyrimidines, taxanes, alkylating agents, vinka alkaloids were reported to induce different clinical manifestations of cardioxicity. Chest radiotherapy is also associated with various forms of cardiac damage, which are indistinguishable from those found in patients with heart disease of other aetiologies and that may even appear several years after administration. Among diagnostic techniques, echocardiography is a noninvasive, cost-effective, and widely available imaging tool. Nuclear imaging and cardiac magnetic resonance may be used but are not so widely available and are more difficult to perform. Finally, some biomarkers, such as troponins, may be used to evaluate cardiac damage, but establishing the optimal timing of troponin assessment remains unclear and defining the cut-off point for positivity is still an important goal. CONCLUSIONS: Cardiotoxicity of anti-cancer treatments is associated with development of heart failure. Novel diagnostic tools might be relevant to early recognize irreversible forms cardiac diseases.

Mutation Analysis of PRKAR1A Gene in a Patient with Atrial Myxoma.

BACKGROUND: Intracardiac myxomas are frequent benign tumors of the heart and typically localize in the left atri- um and interatrial septum. When myxomas generate at other sites, they are designated as atypical. Mutations in the PRKAR1A gene (a tumor suppressor gene that encodes a protein kinase A [PKA] regulatory 1-alpha subunit) have been identified in both syndromic and non-syndromic cardiac atypical myxomas. METHODS: We report the case of a 33-year old woman suffering from night fever, weight loss, asthenia, and progressive dyspnea. RESULTS: The blood laboratory tests revealed microcytic anemia, leukocytosis, thrombocytosis, increased serum levels of C-reactive protein level, and negative blood cultures. Physical examination also demonstrated a 2/6 systolic murmur. Transthoracic and trans-esophageal echocardiography showed a voluminous, mobile mass in the left atrium with a secondary dynamic obstruction of the left cardiac chamber and a significant functional mitral stenosis. A myxoma was supposed and the patient underwent surgery. Histologically, the lesion was identified as myxomatous tumor with gelatinous pattern. No germline mutations of the PRKAR1A gene were detected. The postoperative course did not present any complications, and the patient was discharged on the sixth postoperative day in good clinical condition. Accordingly, there was an improvement in the laboratory tests' results and a resolution of symptoms. CONCLUSIONS: The patient presented an atrial giant gelatinous myxoma with peculiarity of fever of unknown origin, without PRKAR1A gene germline mutations.

Update on the efficacy of statin treatment in acute coronary syndromes.

BACKGROUND: The natural history of atherosclerosis might involve coronary plaque rupture/erosion, thrombus formation and vessel lumen occlusion, clinically recognized as acute coronary syndrome (ACS). International guidelines strongly recommend early statin administration in patients admitted for ACS. In addition to lowering circulating levels of low-density lipoprotein cholesterol (LDL-c), statin treatment was shown to promote plaque stabilization or regression in several ways, including reduction in necrotic lipid core, anti-inflammatory effects and improvement in endothelial function. The aim of this review is to summarize clinical evidence on the role of statins in secondary prevention of ACS. MATERIALS AND METHODS: This narrative review is based on the material found on medline and pubmed up to August 2013. We looked for the terms 'statin, acute coronary syndromes' in combination with 'atherosclerosis, acute myocardial infarction, pathophysiology'. RESULTS: This review article emphasizes the relevance of the timing of statin administration to improve the outcomes after ACS. Early and continuous statin administration has emerged as key features to prevent adverse events, especially in patients admitted for ACS undergoing percutaneous coronary intervention. Clinical trials matching the improved clinical outcome with the imaging of atherosclerotic plaque stabilization/regression, further supporting the effectiveness of statin therapy. However, the achievement of these goals requires high dose of statins, thus increasing the risk of adverse events. CONCLUSIONS: Although clinical trials and meta-analyses have provided conflicting results, it is likely that in clinical practice, the rate of adverse events is higher, so that many concerns still remain about a statin high-dose approach in ACS patients.

Inferior vena cava parameters predict re-admission in ischaemic heart failure.

BACKGROUND: The clinical history of heart failure (HF) is usually characterized by frequent hospitalizations for decompensation. Therefore, several markers of subclinical hemodynamic congestion are under investigation for predicting early rehospitalization. In this field, the potential of ultrasound inferior vena cava (IVC) assessment has been recently investigated in HF but not yet assessed in the different aetiological categories. MATERIAL AND METHODS: Forty-eight patients admitted for decompensated HF (n = 25 with ischaemic heart disease [IHD] and n = 23 non-IHD) underwent biochemical examination (including NT-proBNP), echocardiography and IVC assessment by hand-carried ultrasound (HCU). During 60-day follow-up after discharge, the re-hospitalization rate for HF was recorded to investigate the predictive power of NT-proBNP and IVC assessment among the two study groups. RESULTS: IHD and non-IHD patients with HF were similar except for gender distribution. During follow-up, 16·7% of patients were rehospitalized for decompensated HF, with higher prevalence in IHD group (28% vs. 4·3% P = 0·031). IVC assessment at discharge significantly predicted re-admission in the overall population and in IHD group, whereas NT-proBNP failed to predict rehospitalization in IHD group. In adjusted hazard ratio, only IVC min and the changes of IVC from admission significantly predicted re-admission. ROC analysis confirmed the change in IVC min as the best predictor of rehospitalization in patients with IHD. CONCLUSION: This pilot study showed a higher early re-admission rate in patients with HF due to IHD. In addition, the change in IVC min diameter from admission to discharge was the best predictor of re-admission in patients with IHD.

Is Takotsubo cardiomyopathy still looking for its own nosological identity?

Despite several efforts to provide a proper nosological framework for Takotsubo cardiomyopathy (TCM), this remains an unresolved matter in clinical practice. Several clinical, pathophysiologic and histologic findings support the conceivable hypothesis that TCM could be defined as a unique pathologic entity, rather than a distinct subset of myocardial infarction with non-obstructive coronary arteries. Further investigations are needed in order to define TCM with the most appropriate disease taxonomy.

Pregnancy-related acute myocardial infarction: a review of the recent literature.

Pregnancy-related acute myocardial infarction is a rare and potentially life-threatening cardiovascular event, the incidence of which is growing due to the heightened prevalence of several risk factors, including increased maternal age. Its main aetiology is spontaneous coronary artery dissection, which particularly occurs in pregnancy and may engender severe clinical scenarios. Therefore, despite frequently atypical and deceptive presentations, early recognition of such a dangerous complication of gestation is paramount. Notwithstanding diagnostic and therapeutic improvements, pregnancy-related acute myocardial infarction often carries unfavourable outcomes, as emergent management is difficult owing to significant limitations in the use of ionising radiation-e.g. during coronary angiography, potentially harmful to the foetus even at low doses. Notably, however, maternal mortality has steadily decreased in recent decades, indicating enhanced awareness and major medical advances in this field. In our paper, we review the recent literature on pregnancy-related acute myocardial infarction and highlight the key points in its management.

Cannabinoid Effect and Safety in Spasticity Following Stroke: A Double-Blind Randomized Placebo-Controlled Study.

Background: Nabiximols is a cannabis-based drug to treat spasticity-associated symptoms currently approved for patients with multiple sclerosis only. Cannabinoids are useful in an increasing number of medical conditions but may bear an increased risk for cardiovascular events. SativexStroke is a double-blind randomized placebo-controlled crossover monocentric clinical trial investigating the efficacy and safety of nabiximols in patients with spasticity following stroke. Methods: Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Cardiovascular safety was assessed before and during the trial. Primary endpoints were changes in spasticity numeric rating scale scores and electromyographic recording of the stretch reflex in affected wrist flexors. Secondary outcome measures were numeric rating scale scores for pain, sleep and bladder function, the number of daily spasms and clinical assessment of spasticity with the modified Ashworth scale. The study was registered with the EudraCT number 2016-001034-10. Results: Between May 2, 2018, and February 20, 2020, 41 patients entered the study. Seven patients did not complete the study, so 34 were included in the analysis. Two serious adverse events occurred, but none related to cardiovascular function. Primary and secondary efficacy outcome measures did not change from baseline during nabiximols treatment relative to placebo. Conclusion: This study suggests that nabiximols use is probably safe in stroke patients, therefore cannabinoid usefulness may be further investigated. The lack of nabiximols effect could be related to low pain levels in recruited patients or different spasticity mechanisms between post-stroke and multiple sclerosis patients. Similarly, a beneficial effect of nabiximols could have emerged if more patients with a higher level of spasticity at baseline were recruited. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001034-10/IT.

Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study.

Background: Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk. Methods: This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10. Results: Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition. Conclusion: This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates.

Cardiac Outpouchings: Definitions, Differential Diagnosis, and Therapeutic Approach.

BACKGROUND AND AIMS: Cardiac outpouchings encounter a series of distinct congenital or acquired entities (i.e. aneurysms, pseudoaneurysms, diverticula, and herniations), whose knowledge is still poorly widespread in clinical practice. This review aims to provide a comprehensive overview focusing on definition, differential diagnosis, and prognostic outcomes of cardiac outpouchings, as well as further insights on therapeutic options, in order to assist physicians in the most appropriate decision-making. METHODS: The material reviewed was obtained by the following search engines: MEDLINE (PubMed), EMBASE, Google Scholar, and Clinical Trials databases, from January 1966 until March 2021. We searched for the following keywords (in title and/or abstract): ("cardiac" OR "heart") AND ("outpouching" OR "outpouch" OR "aneurysm" OR "pseudoaneurysm" OR "false aneurysm" OR "diverticulum" OR "herniation"). Review articles, original articles, case series, and case reports with literature review were included in our search. Data from patients with congenital or acquired cardiac outpouchings, from prenatal to geriatric age range, were investigated. RESULTS: Out of the 378 papers initially retrieved, 165 duplicates and 84 records in languages other than English were removed. Among the 129 remaining articles, 76 were included in our research material, on the basis of the following inclusion criteria: (a) papers pertaining to the research topic; (b) peer-reviewed articles; (c) using standardized diagnostic criteria; and (d) reporting raw prevalence data. Location, morphologic features, wall motion abnormalities, and tissue characterization were found to have a significant impact in recognition and differential diagnosis of cardiac outpouchings as well as to play a significant role in defining their natural history and prognostic outcomes. CONCLUSIONS: Careful recognition of cardiac outpouchings remains a diagnostic challenge in clinical practice. Due to a broad cluster of distinctive and heterogeneous entities, their knowledge and timely recognition play a pivotal role in order to provide the most appropriate clinical management and therapeutic approach.