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.
To compare the efficacy and safety of different mechanical circulatory support (MCS) devices in CS. A total of 24 studies (7 randomized controlled trials—RCTs—and 17 non-RCTs) involving 11,117 ...patients were entered in a Bayesian network meta-analysis. The primary endpoint was 30-day mortality. Secondary endpoints were stroke and bleeding (requiring transfusion and/or intracranial and/or fatal). Compared with no MCS, extra-corporeal membrane oxygenation (ECMO) reduced 30-day mortality when used both alone (OR 0.37, 95% CrI 0.15–0.90) and together with the micro-axial pump Impella (OR 0.13, 95% CrI 0.02–0.80) or intra-aortic balloon pump (IABP) (OR 0.19, 95% CrI 0.05–0.63), although the relevant articles were affected by significant publication bias. Consistent results were obtained in a sensitivity analysis including only studies of CS due to myocardial infarction. After halving the weight of studies with a non-RCT design, only the benefit of ECMO + IABP on 30-day mortality was maintained (OR 0.22, 95% CI 0.057–0.76). The risk of bleeding was increased by TandemHeart (OR 13, 95% CrI 3.50–59), Impella (OR 5, 95% CrI 1.60–18), and IABP (OR 2.2, 95% CrI 1.10–4.4). No significant differences were found across MCS strategies regarding stroke. Although limited by important quality issues, the studies performed so far indicate that ECMO, especially if combined with Impella or IABP, reduces short-term mortality in CS. MCS increases the hazard of bleeding.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Aim
To provide an updated assessment of the efficacy–safety profile of very short (1 or 3 months) dual antiplatelet therapy (DAPT) compared with long (12 months) DAPT in patients undergoing ...percutaneous coronary interventions (PCIs).
Methods and results
Seven randomized controlled trials (RCTs) comparing very short vs. long DAPT in 35 785 patients undergoing PCI were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint trial-defined major bleeding through at least 1 year. Compared with longer duration, very short DAPT yielded comparable rates of MACE odds ratio (OR) 0.93, 95% confidence interval (CI) 0.84–1.03, P = 0.19, all-cause mortality (OR 0.92, 95% CI 0.80–1.06, P = 0.25), myocardial infarction (OR 1.01, 95% CI 0.88–1.15, P = 0.91), stroke (OR 1.04, 95% CI 0.72–1.50, P = 0.83), stent thrombosis (OR 1.05, 95% CI 0.80–1.37, P = 0.73), target vessel revascularization (OR 0.99, 95% CI 0.82–1.18, P = 0.89), and comparable net clinical benefit (OR 0.92, 95% CI 0.84–1.01, P = 0.08). Very short DAPT was associated with reduced rates of major bleeding (OR 0.61, 95% CI 0.40–0.94, P = 0.03) or any bleeding (OR 0.65, 95% CI 0.47–0.90, P = 0.009). Subgroup analyses showed consistent results for 1 vs. 3 month DAPT and for aspirin vs. P2Y12 inhibitor monotherapy following very short DAPT.
Conclusions
Compared with long DAPT, very short DAPT did not increase the odds of ischaemic complications, while reducing the odds of major or any bleeding by over 30%.
Aims
We systematically reviewed the European real‐world evidence (RWE) about sacubitril‐valsartan for heart failure with reduced ejection fraction.
Methods and results
Twenty‐one articles, including ...16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM‐HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random‐effects model meta‐analysis, age was higher (mean difference +3.84, 95% CI 1.92–5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64–0.91), hypertension (OR 0.55, 95% CI 0.37–0.82), and diabetes (OR 0.77, 95% CI 0.64–0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27–5.53) in real‐life than in PARADIGM‐HF. Other clinical and medical features were presented in 19–76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril‐valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23–47) and discontinued in 12.8% (95% CI 7.4–18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all‐cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5–19)/100 person‐year, 8 (95% CI 4–12)/100 person‐year, and 24 (95% CI 5–42)/100 person‐year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects).
Conclusions
Limited‐quality RWE indicates that there are important differences between European patients prescribed sacubitril‐valsartan and the PARADIGM‐HF population, including the frequency of target dose achievement.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
We assessed the diagnostic yield of genetic testing and the relationship of left ventricular (LV) reverse remodelling (LVRR) with the presence of DNA pathogenic (P) or likely pathogenic (LP) ...variants in patients with dilated cardiomyopathy (DCM).
Methods and results
From 680 outpatients followed at the Heart Failure Outpatient Clinic of our institution, we selected subjects with a diagnosis of DCM as defined by LV ejection fraction (LVEF) ≤40% and LV dilatation not explained by coronary artery disease or other causes. All patients were offered genetic investigation of 42 disease‐associated DCM genes with next‐generation sequencing. Seventy patients fulfilled the definition of DCM and 66 underwent genetic investigation. We identified 18 P/LP variants in 16 patients, with a diagnostic yield of 24%. The most common variants were truncating TTN variants (n = 7), followed by LMNA (n = 3), cytoskeleton Z‐disc (n = 3), ion channel (n = 2), motor sarcomeric (n = 2), and desmosomal (n = 1) genes. After a median follow‐up of 53 months (inter‐quartile range 20–111), patients without P/LP variants exhibited higher systolic and diastolic blood pressure, lower plasma brain natriuretic peptide levels, and a larger extent of LVRR, as reflected by the increase in LVEF (+14% vs. +1%, P = 0.0008) and decrease in indexed LV end‐diastolic diameter (−6.5 vs. −2 mm/m2, P = 0.03) compared with patients with P/LP variants.
Conclusions
Our results confirm the high diagnostic yield of genetic testing in selected DCM patients and suggest that identification of P/LP variants in DCM portends poorer LVRR in response to guideline‐directed medical therapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Right atrial pressure (RAP) can be estimated by echocardiography from inferior vena cava diameter and collapsibility (eRAP
), tricuspid
/
' ratio (
), or hepatic vein flow (eRAP
). The mean of these ...estimates (eRAP
) might be more accurate than single assessments.
eRAP
,
, eRAP
(categorized in 5, 10, 15, or 20 mmHg), eRAP
(continuous values) and invasive RAP (iRAP) were obtained in 43 consecutive patients undergoing right heart catheterization median age 69 (58-75) years, 49% males. There was a positive correlation between eRAP
and iRAP (Spearman test
= 0.66,
< 0.001), with Bland-Altman test showing the best agreement for values <10 mmHg. There was also a trend for decreased concordance between eRAP
,
, eRAP
, and iRAP across the 5- to 20-mmHg categories, and iRAP was significantly different from
and eRAP
for the 20-mmHg category (Wilcoxon signed-rank test
= 0.02 and
< 0.001, respectively). The areas under the curve in predicting iRAP were nonsignificantly better for eRAP
than for eRAP
at both 5-mmHg 0.64, 95% confidence interval (CI) 0.49-0.80 vs. 0.70, 95% CI 0.53-0.87; Wald test
= 0.41 and 10-mmHg (0.76, 95% CI 0.60-0.92 vs. 0.81, 95% CI 0.67-0.96;
= 0.43) thresholds.
Our data suggest that multiparametric eRAP
does not provide advantage over eRAP
, despite being more complex and time-consuming.
Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 ...year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 December 2019 through 15 September 2022. After excluding those with CTEPH, post-capillary PH at the diagnostic right heart catheterization (RHC), and/or incomplete data, 23 (33%) of a total of 69 subjects met the criteria proposed in the AMBITION trial to suspect LHD. Diabetes 9 (39%) vs. 6 (13%), p = 0.01 and chronic kidney disease 14 (61%) vs. 12 (26%), p = 0.003 were more common, and the last RHC pulmonary artery wedge pressure 14 ± 5 vs. 10 ± 3 mmHg, p < 0.001 was higher and pulmonary vascular resistance 5.56 ± 3.31 vs. 8.30 ± 4.80, p = 0.02 was lower in LHD than non-LHD patients. However, PAH therapy was similar, with 13 (57%) and 23 (50%) subjects, respectively, taking two oral drugs. PAH medication patterns remained comparable between LHD and non-LHD patients also when the former 37, 54% were identified by atrial fibrillation and echocardiographic features of LHD, in addition to the AMBITION criteria. In this real-world snapshot, elderly PAH patients were treated with pulmonary vasodilators, including combinations, despite a remarkable prevalence of a LHD phenotype.
Purpose of Review
To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous ...thromboembolism (CAT).
Recent Findings
In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable.
Summary
Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data ...on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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