Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which ...may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.
Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn ...exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic.
Background
Identification of reliable outcome predictors in coronavirus disease 2019 (COVID‐19) is of paramount importance for improving patient's management.
Methods
A systematic review of ...literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in‐hospital mortality. We extracted numeric data on patients’ characteristics and cases with adverse outcomes and employed inverse variance random‐effects models to derive pooled estimates.
Results
We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26‐4.41), acute cardiac (OR = 10.58, 5.00‐22.40) or kidney (OR = 5.13, 1.78‐14.83) injury, increased procalcitonin (OR = 4.8, 2.034‐11.31) or D‐dimer (OR = 3.7, 1.74‐7.89), and thrombocytopenia (OR = 6.23, 1.031‐37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D‐dimer conferred an increased risk of in‐hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934‐6.73), but not with mortality.
Conclusions
Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in‐hospital mortality.
Aims
An algorithm for non‐invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR‐CA) and novel disease‐modifying therapies have prompted an active search for CA. We examined the ...prevalence of CA in different settings based on literature data.
Methods and results
We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non‐cardiac reasons (n = 5 studies), 1% (95% confidence interval CI 0%–1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%–20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%–15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%–4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%–10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%–9%); severe aortic stenosis (n = 7), 8% (95% CI 5%–13%); autopsy series of ‘unselected’ elderly individuals (n = 4), 21% (95% CI 7%–39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR‐CA, but the average percentage of patients with amyloid light‐chain (AL) CA was up to 18%.
Conclusions
Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR‐CA accounts for many cases of CA across the different settings, but AL‐CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women.
Abstract
Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the ...heart and in other organs as amyloid fibrils. Cardiac involvement in TTR-related amyloidosis (ATTR) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction. ATTR is an underdiagnosed disorder as well as a crucial determinant of morbidity and mortality, thus justifying the current quest for a safe and effective treatment. Therapies targeting cardiac damage and its direct consequences may yield limited benefit, mostly related to dyspnoea relief through diuretics. For many years, liver or combined heart and liver transplantation have been the only available treatments for patients with mutations causing ATTR, including those with cardiac involvement. The therapeutic options now include several pharmacological agents that inhibit hepatic synthesis of TTR, stabilize the tetramer, or disrupt fibrils. Following the positive results of a phase 3 trial on tafamidis, and preliminary findings on patisiran and inotersen in patients with ATTR-related neuropathy and cardiac involvement, we provide an update on this rapidly evolving field, together with practical recommendations on the management of cardiac involvement.
Despite the evidence demonstrating the clinical utility of cardiac specific biomarkers in improving cardiovascular risk evaluation in several clinical conditions, even the most recent reviews and ...guidelines fail to consider their measurement in order to enhance the accuracy of the evaluation of cardiovascular risk in pregnant women. The aim of this review article was to examine whether the assay of cardiac specific biomarkers can enhance cardiovascular risk evaluation in pregnant women, first by reviewing the relationships between the physiological state of pregnancy and cardiac specific biomarkers. The clinical relevance of brain natriuretic peptide (BNP)/NT-proBNP and high-sensitivity cardiac troponin I/high-sensitivity cardiac troponin T (hs-cTnI/hs-cTnT) assay in improving cardiovascular risk evaluation is examined based on the results of clinical studies on subjects with normal and those with complicated pregnancy. Finally, the analytical approaches and clinical objectives related to cardio specific biomarkers are advocated in order to allow an early and more accurate evaluation of cardiovascular risk in pregnant women.
The term "inflammageing" was introduced in 2000, with the aim of describing the chronic inflammatory state typical of elderly individuals, which is characterized by a combination of elevated levels ...of inflammatory biomarkers, a high burden of comorbidities, an elevated risk of disability, frailty, and premature death. Inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and rapid progression to heart failure. The great experimental and clinical evidence accumulated in recent years has clearly demonstrated that early detection and counteraction of inflammageing is a promising strategy not only to prevent cardiovascular disease, but also to slow down the progressive decline of health that occurs with ageing. It is conceivable that beneficial effects of counteracting inflammageing should be most effective if implemented in the early stages, when the compensatory capacity of the organism is not completely exhausted. Early interventions and treatments require early diagnosis using reliable and cost-effective biomarkers. Indeed, recent clinical studies have demonstrated that cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins) are able to identify, even in the general population, the individuals at highest risk of progression to heart failure. However, further clinical studies are needed to better understand the usefulness and cost/benefit ratio of cardiac-specific biomarkers as potential targets in preventive and therapeutic strategies for early detection and counteraction of inflammageing mechanisms and in this way slowing the progressive decline of health that occurs with ageing.
•ACEi/ARB and MRA can be safely used in cardiac amyloidosis•Treatment must be started at a low dose and slowly up-titrated•Patients must be monitored quite closely•Beta-blockers are less tolerated in ...AL amyloidosis and/or worse haemodynamic function
Drugs for neurohormonal antagonism are usually denied to patients with cardiac amyloidosis (CA) because of safety concerns.
Patients diagnosed with CA at a tertiary referral centre from 2009 to 2019 were enrolled. In the absence of contraindications, beta-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB), and mineralocorticoid receptor antagonists (MRA) were started or up-titrated.
99 patients were evaluated (72% men, age 80 years 72,83, 33% light-chain and 67% transthyretin amyloidosis); 56% were started on or underwent up-titration of a beta-blocker, 25% of ACEi/ARB, and 39% of MRA; beta-blockers were then prescribed to 87% of patients, ACEi/ARB to 75%, and MRA to 63%, with median bisoprolol, ramipril, valsartan, and spironolactone daily equivalent doses of 2.5 mg, 5 mg, 80 mg, and 25 mg, respectively. Patients starting or starting/up-titrating a beta-blocker did not show a higher frequency of hypotension, fatigue, syncope, symptomatic bradycardia, need for pacemaker implantation, or HF hospitalization. Lower stroke volume and cardiac output (CO) predicted HF hospitalization regardless of amyloidosis type; lower left ventricular ejection fraction predicted hypotension, and lower CO and diastolic blood pressure predicted syncope. Patients who had an ACEi/ARB or MRA being started or up-titrated did not experience more adverse events than other patients.
ACEi/ARB and MRA can be safely used in CA, provided that no contraindications are present, treatment is started at a low dose and slowly up-titrated, and patients are monitored quite closely. Beta-blocker therapy is less tolerated in patients with AL amyloidosis and/or worse haemodynamic function.
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