Whether guided selection of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) is effective in improving outcomes compared with standard antiplatelet therapy remains ...controversial. We assessed the safety and efficacy of guided versus standard selection of antiplatelet therapy in patients undergoing PCI.
For this systematic review and meta-analysis, from Aug 20 to Oct 25, 2020, we searched MEDLINE (via PubMed), Cochrane, Embase, and Web of Science databases for randomised controlled trials and observational studies published in any language that compared guided antiplatelet therapy, by means of platelet function testing or genetic testing, versus standard antiplatelet therapy in patients undergoing PCI. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. Risk ratios (RRs) and 95% CIs were used with random-effects or fixed-effect models according to the estimated heterogeneity among studies assessed by the I2 index. Coprimary endpoints were trial-defined primary major adverse cardiovascular events and any bleeding. Key secondary endpoints were all-cause death, cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and major and minor bleeding. This study is registered with PROSPERO (CRD42021215901).
3656 potentially relevant articles were screened. Our analysis included 11 randomised controlled trials and three observational studies with data for 20 743 patients. Compared with standard therapy, guided selection of antiplatelet therapy was associated with a reduction in major adverse cardiovascular events (RR 0·78, 95% CI 0·63–0·95, p=0·015) and reduced bleeding, although not statistically significant (RR 0·88, 0·77–1·01, p=0·069). Cardiovascular death (RR 0·77, 95% CI 0·59–1·00, p=0·049), myocardial infarction (RR 0·76, 0·60–0·96, p=0·021), stent thrombosis (RR 0·64, 0·46–0·89, p=0·011), stroke (RR 0·66, 0·48–0·91, p=0·010), and minor bleeding (RR 0·78, 0·67–0·92, p=0·0030) were reduced with guided therapy compared with standard therapy. Risks of all-cause death and major bleeding did not differ between guided and standard approaches. Outcomes varied according to the strategy used, with an escalation approach associated with a significant reduction in ischaemic events without any trade-off in safety, and a de-escalation approach associated with a significant reduction in bleeding, without any trade-off in efficacy.
Guided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI.
None.
Long-term effects of Coronavirus Disease of 2019 (COVID-19) are of utmost relevance.
We aimed to determine: 1) the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing ...(CPET); 2) the characteristics associated with cardiopulmonary exercise testing (CPET) performance; 3) the safety and tolerability of CPET.
We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 from Azienda Sanitaria Locale 3, Genoa. Three months after hospital discharge a complete clinical evaluation, trans-thoracic echocardiography, CPET, pulmonary function tests, and dominant leg extension (DLE) maximal strength measurement were performed.
From the 225 patients discharged alive from March to November 2020, we excluded 12 incomplete/missing cases and 13 unable to perform CPET, leading to a final cohort of 200. Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3–103.1).
Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value.
Among the 99 patients with reduced %pVO2, 61 (61%) had a normal anaerobic threshold: of these, 9(14.8%) had respiratory, 21(34.4%) cardiac, and 31(50.8%) non-cardiopulmonary reasons for exercise limitation. Inerestingly, 80% of patients experienced at least one disabling symtpom, not related to %pVO2 or functional capacity.
Multivariate linear regression showed percent-predicted forced expiratory volume in one-second(β = 5.29,p = 0.023), percent-predicted diffusing capacity of lungs for carbon monoxide(β = 6.31,p = 0.001), and DLE maximal strength(β = 14.09,p = 0.008) to be independently associated with pVO2.
No adverse event was reported during or after CPET, and no involved health professional developed COVID-19.
At three months after discharge, about 1/3rd of COVID-19 survivors show functional limitations, mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.
•Long-term effects of COVID-19 are of utmost relevance.•At 3 months half of COVID-19 patients previously discharged home have significant reduction in peak oxygen consumption at cardiopulmonary exercise test.•One third of them has no cardio-pulmonary cause as the principal mechanism of CPET impairment.•Four out of five experience at least one disabling symptom at 3-month evaluation.•Symptoms are not related with abnormal peak oxygen consumption or functional capacity.
Background and aim. During ageing, the prevalence of dementia, and especially of Alzheimer’s disease (AD) and cardiovascular disease (CVD), increases. The aim of this review is to investigate the ...relationship between AD and CVD and its risk factors, with a view to explain the underlying mechanisms of this association. Methods. 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,” and “heart failure.” Out of the 1,328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed. Among the 681 remaining studies, 98 were included in our research material on the basis of the following inclusion criteria: (a) the community-based studies; (b) using standardized diagnostic criteria; (c) reporting raw prevalence data; (d) with separate reported data for sex and age classes. Results. While AD and CVD 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 vascular factors on these diseases. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being hypoperfusion and emboli, atherosclerosis, and the fact that, in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. Conclusions. AD and CVD are frequently associated. Further studies are needed in order to understand the effect of CVD and its risk factors on AD in order to better comprehend the effects of subclinical and clinical CVD on the brain. Finally, we need to clarify the impact of the underlying hypothesized mechanisms of this association and to investigate gender issues.
: Scientific evidence on subjects treated with statin or other lipid-lowering treatments has established that treatments aiming to lower low-density lipoprotein cholesterol (LDL-C) can reduce ...atherosclerosis. PCSK9 inhibitors (PCSK9-i), thanks to their efficacy in reducing LDL-C constitute a further step in the treatment of dyslipidemia and cardiovascular (CV) diseases.
: The purpose of this narrative review is to summarize the current knowledge of PCSK9-i, with particular regard to pharmacodynamic, pharmacokinetic, and clinical data on evolocumab and alirocumab.
: PCSK9-I are effective in reducing atherosclerotic events through their significant LDL-C-lowering action similarly to statins. Furthermore, these drugs can be considered safe and well-tolerated. However, some controversies remain with regard to their efficacy in reducing mortality and the paucity of data on both pleiotropic effects and long-term safety of these drugs. However, future studies will focus on understanding the effects of very low cholesterol levels on health. At present, we know that the genetic model of PCSK9 deficiency is characterized by very low LDL-C levels without particular health problems. Yet, we do not know the effect of prolonged PCSK9 inhibition induced by antibody action during the lifetime of normal subjects.
Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown.
The ...authors sought to assess the role of hyaluronan (HA) metabolism in ACS.
Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis.
Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively).
HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.
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Bilateral carpal tunnel syndrome (CTS), particularly in male individuals with left ventricular hypertrophy (LVH), has been recognized as a red flag for transthyretin cardiac amyloidosis (TTR-CA). ...Nonetheless, the opportunity of screening CTS patients for TTR has yet to be determined.
Medical records of 1689 CTS surgeries performed at our institution between 2008 and 2018 were reviewed. Eighty-three males who underwent bilateral CTS surgery were considered eligible for the study, and offered a screening examination including electrocardiography and echocardiography. Individuals with LVH (diastolic septal wall thickness > 12 mm) were offered second-line diagnostic testing including blood testing and bone scintigraphy.
Study population consisted of 53 bilateral CTS male patients, with median age of 73 years. LVH was found in 6 (11%) individuals. None of them had monoclonal gammopathy or reported CTS occupational risk factors. Two declined to undergo further testing, whereas 2 had negative and 2 had positive bone scintigraphy (both Perugini 2 uptake) and tested negative for TTR gene mutations (wild-type TTR-CA).
Prevalence of TTR-CA in the entire study population was 4%, but among bilateral CTS patients with LVH peaked at 33%. In this latter population, screening for TTR-CA appeared feasible and effective.
•Bilateral carpal tunnel syndrome (CTS), in particular in males, is a red flag suggesting a diagnosis of transthyretin cardiac amyloidosis (TTR-CA).•We investigated the presence of TTR-CA in male individuals who had undergone bilater CTS surgery.•Prevalence of TTR-CA in the entire study population was 4%, but among bilateral CTS patients with left ventricular hypertrophy peaked at 33%.
Immune-checkpoint inhibitors (ICIs) represent a successful paradigm in the treatment of cancer. ICIs elicit an immune response directed against cancer cells, by targeting the
immune checkpoints, key ...regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Such response, however, is not entirely tumor-specific and may result in immune-related adverse events (irAEs), involving a number of organs and systems. Cardiovascular (CV) irAEs are rare, although potentially severe. In particular, several cases of ICI-related myocarditis with life-threatening course have been reported: the possibility of fulminant cases, thus, requires a high level of awareness among both oncologists and cardiologists. Aggressive work-up and management of symptomatic patients taking ICIs is fundamental for early recognition and initiation of specific immunosuppressive therapies. Notably, myocarditis occurs within few weeks from ICIs initiation, offering opportunity for a targeted screening. Troponin testing is the cornerstone of this screening, yet uncertainties remain regarding timing and candidates. Moreover, troponins positivity should be carefully interpreted. We herein review the main aspects of ICI-related myocarditis and suggest a practical approach. In particular, we focus on the opportunities that a baseline CV evaluation offers for subsequent management by collecting clinical and instrumental data, essential for the interpretation of troponin results, for differential diagnosis and for the formulation of a diagnostic and therapeutic workup.
Background
Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.
Methods
Data were ...retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between
d
-dimer levels and PE incidence was evaluated using restricted cubic splines models.
Results
The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission
d
-dimer 4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL,
p
< 0.001. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%,
p
< 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%,
p
= 0.06). In multivariate regression, only
d
-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62;
p
= 0.01). The relation between
d
-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline
d
-dimer < 500 ng/mL.
Conclusions
PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of
d
-dimer in this population need to be clarified.
Graphic abstract
To clarify the meaning of elevated cardiac troponin in elite soccer athletes previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and screened for cardiovascular ...involvement in the wake of competitive sport resumption.
We designed a retrospective cohort study with the collaboration of two Italian Serie A teams. Soccer players from both rosters (58 athletes) were systematically analysed. For every SARS-CoV-2 positive athlete, the Italian Soccer Federation protocol requested full blood tests including high-sensitivity cardiac troponin I (hs-cTnI), along with a complete cardiovascular examination. We extended the analysis to SARS-CoV-2 negative athletes.
A total of 13/58 players (22.4%) suffered from SARS-CoV-2infection: all had a negative cardiovascular examination and 2/13 (15%) showed increased hs-cTnI values (120.8 pg/ml and 72,6 pg/ml, respectively; upper reference level 39.2 pg/ml), which did not track with inflammatory biomarkers. Regarding the 45/58 (77.6%) non infected athletes, a slight increase in hs-cTnI was observed in 2 (4.5%) subjects (values: 61 pg/ml and 75 pg/ml respectively). All hs-cTnI positive athletes (4/58, 7%) underwent cardiac magnetic resonance (CMR), that excluded any cardiac injury.
In our retrospective study, SARS-CoV-2 infection in elite soccer athletes was not associated to clinical or biomarkers abnormalities. Increased hs-cTnI was rare and not significantly associated with previous SARS-COV2 infection nor with pathological findings at CMR, albeit elevated hs-cTnI was numerically more prevalent in the infected group.
•The meaning of elevated hs-cTnI in elite athletes previously infected with coronavirus disease 2019 (COVID-19) is unknown.•In our cohort or previously infected professional soccer players, increased hs-cTnI was was was not associated to abnormalities at electrocardiogram and echocardiography, nor at cardiac magnetic resonance imaging.
In the expanding world of cardiovascular diseases, rapidly reaching pandemic proportions, the main focus is still on coronary atherosclerosis and its clinical consequences. However, at least in the ...Western world, middle-aged male patients with acute myocardial infarction are no more the rule. Due to a higher life expectancy and major medical advances, physicians are to treat older and frailer individuals, usually with multiple comorbidities. In this context, myocardial ischaemia and infarction frequently result from an imbalance between myocardial oxygen supply and demand—i.e., type 2 myocardial infarction (T2MI), according to the current universal definition—rather than coronary atherothrombosis. Moreover, the increasing use of high-sensitivity cardiac troponin assays has led to a heightened detection of T2MI—often causing relatively little myocardial injury—, which seems to have doubled its numbers in recent years. Nevertheless, owing to its multifaceted pathophysiology and clinical presentation, T2MI is still underdiagnosed. Perhaps more importantly, T2MI is also victim of undertreatment, as drugs that constitute the cornerstone of therapy in most cardiovascular diseases are much more unlikely to be prescribed in T2MI than in coronary atherothrombosis. In this paper, we review the recent literature on the classification, pathophysiology, epidemiology, and management of T2MI, trying to summarise the state-of-the-art knowledge about this increasingly important pathologic condition. Finally, based on the current scientific evidence, we also propose an algorithm that may be easily utilised in clinical practice, in order to improve T2MI diagnosis and risk stratification.
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