The study aims to evaluate the applicability in the real world of randomised clinical trials (RCT) on antithrombotic treatment in patients with cardiovascular disease (CVD) and peripheral artery disease (PAD).
According to this analysis, trial-based guideline recommendations largely apply to real-world patients, especially for PAD. They also demonstrated how in a cohort of patients with established CVD, long-term risk of recurrent cardiovascular events, major bleeding and all-cause death are mostly similar for eligible...]]>
Takotsubo syndrome (TTS) is an acute heart failure syndrome, featured by transient left ventricular systolic dysfunction. Recurrences of TTS are not infrequent and there is no standard preventive therapy. The aim of this study was to evaluate in a network meta-analysis if beta-blockers (BB) and ACE inhibitors/angiotensin receptor blockers (ACEi/ARBs), in combination or not, can effectively prevent TTS recurrences.
We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for clinical studies published between January 2010 and September 2022. We considered all those studies including patients receiving medical therapy with BB, ACEi/ARBs. The primary outcome was TTS recurrence.
We identified 6 clinical studies encompassing a total of 3407 patients with TTS. At 40±10 months follow-up, TTS recurrence was reported in 160 (4.7%) out of 3407 patients. Mean age was 69.8±2 years and 394 patients (11.5%) out of 3407 were male. There were no differences in terms of TTS recurrence when comparing ACEi/ARBs versus control (OR 0.83; 95% CI 0.47 to 1.47, p=0.52); BB versus control (OR 1.01; 95% CI 0.63 to 1.61, p=0.96) and ACEi/ARBs versus BB (OR 0.88; 95% CI 0.51 to 1.53, p=0.65).
Combination of BB and ACEi/ARBs was also not effective in reducing the risk of recurrence versus control (OR 0.91; 95% CI 0.58 to 1.43, p=0.68) vs ACEi/ARBs (OR 0.79; 95% CI 0.46 to 1.34, p=0.38)) and vs BB (OR 0.77; 95% CI 0.49 to 1.21, p=0.26).
Our study did not find sufficient statistical evidence regarding combination therapy with BB and ACEi/ARBs in reduction of TTS recurrence.
Assessment of generalisability of guideline-informing trials on antithrombotic treatment intensification to real-world patients with cardiovascular disease (CVD).
Inclusion and exclusion criteria of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS), Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA), Prevention of Cardiovascular events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction (PEGASUS-TIMI) and Dual Antiplatelet Therapy (DAPT) study were applied to coronary artery disease (CAD) and/or peripheral artery disease (PAD) patients from Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) to determine real-world eligibility. Eligible and ineligible patients were compared on baseline characteristics, cardiovascular events, major bleeding and mortality.
Eligibility ranged from 11%–94% for CAD to 75%–90% for patients with PAD. Cardiovascular, bleeding and mortality risks were higher in COMPASS-eligible patients with CAD (rate ratios (RR) 1.98 (95% CI 1.74 to 2.26), 2.02 (95% CI 1.47 to 2.78) and 3.11 (95% CI 2.71 to 3.57), respectively) and CHARISMA-eligible patients (RR 1.51 (95% CI 1.12 to 2.06), 2.25 (95% CI 1.01 to 6.21) and 4.43 (95% CI 2.79 to 7.51), respectively), and lower in COMPASS-eligible patients with PAD (RR 0.45 (95% CI 0.36 to 0.56), 0.29 (95% CI 0.18 to 0.46) and 0.45 (95% CI 0.38 to 0.54), respectively) and DAPT-eligible patients with CAD (RR CVD 0.49 (95% CI 0.34 to 0.69) and mortality 0.67 (95% CI 0.48 to 0.94)) than ineligible patients. After adjustment for trial eligibility criteria, only higher cardiovascular and mortality risks in COMPASS-eligible patients with CAD and lower cardiovascular risks in CHARISMA-eligible and DAPT-eligible patients persisted with CAD.
A large proportion of contemporary CVD patients would be eligible for intensified antithrombotic treatment trials, with mostly similar adjusted event risks to ineligible patients. Trial-based guideline recommendations are largely applicable to real-world patients.
Pulmonary hypertension (PH) is a common complication in patients with complete dextro-transposition of the great arteries (TGA) after atrial switch (D-TGA/AS) and congenitally corrected TGA (ccTGA). In this population with subaortic right ventricles (sRVs), echocardiography is a poor screening tool for PH; implantable invasive haemodynamic monitoring (IHM) could be used for this purpose, but data are limited. The aim of this study is to report on novel uses of IHM in patients with sRV.
This retrospective study describes the uses of IHM, impact of IHM on heart failure hospitalisation (HFH) and device-related complications in adults with sRV from a single centre (2015–2022).
IHM was placed in 18 patients with sRV (median age 43 (range 30–54) years, 8 female, 16 with D-TGA/AS, 2 with ccTGA); 16 had moderate or severe sRV systolic dysfunction, 13 had PH on catheterisation. IHM was used for (1) Medical therapy titration, (2) Medical management after ventricular assist device in patients with transplant-limiting PH and (3) Serial monitoring of pulmonary artery pressures without repeat catheterisations to help identify the optimal time for heart transplant referral. In follow-up (median 23 months), HFHs/year were similar to the year prior to IHM (median 0 (IQR 0–1.0) before vs 0 (0–0.8) after, p=0.984). Device migration occurred in one, without long-term sequelae.
Uses of IHM in patients with sRV are described which may minimise the need for serial catheterisations in a population where PH is prevalent. HFHs were low overall but not impacted by IHM. One device-related complication occurred without long-term consequence.
To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).
Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months.
The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9–2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9–72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01).
A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference.
A woman in her mid-40s with a recent diagnosis of pulmonary embolism (on rivaroxaban) presented to the emergency room with dyspnea and fatigue. Vital signs were stable on arrival but a new holosystolic murmur was noted on exam and labs revealed pancytopenia. Infectious workup was unrevealing. CT revealed stable pulmonary emboli compared with prior imaging, along with a new splenic infarct. Transthoracic echocardiography (TTE) (
Transthoracic echocardiography on admission—parasternal long view.
Transthoracic echocardiography on admission—apical four-chamber view.
Growth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS).
GDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087–1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up.
In patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations.
High GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information.
This study investigates mitral annular disjunctions (MAD) in the atrial wall-mitral annulus-ventricular wall junction along the mural mitral leaflet and commissures.
We examined 224 adult human hearts (21.9% females, 47.9±17.6 years) devoid of cardiovascular diseases (especially mitral valve disease). These hearts were obtained during forensic medical autopsies conducted between January 2018 and June 2021. MAD was defined as a spatial displacement (≥2 mm) of the leaflet hinge line towards the left atrium. We provided a detailed morphometric analysis (disjunction height) and histological examination of MADs.
MADs were observed in 19.6% of all studied hearts. They appeared in 12.1% of mural leaflets. The P1 scallop was the primary site for disjunctions (8.9%), followed by the P2 scallop (5.4%) and P3 scallop (4.5%). MADs were found in 9.8% of all superolateral and 5.8% of all inferoseptal commissures. The average height for leaflet MADs was 3.0±0.6 mm, whereas that for commissural MADs was 2.1±0.5 mm (p<0.0001). The microscopical arrangement of MADs in both the mural leaflet and commissures revealed a disjunction shifted towards left atrial aspect, filled with connective tissue and covered by elongated valve annulus. The size of the MAD remained remarkably uniform and showed no correlation with other anthropometric factors (all p>0.05).
In the cohort of the patients with healthy hearts, MAD is present in about 20% of all studied hearts. The MADs identified tend to be localised, confined to a single scallop. Moreover, MADs in the commissures are notably smaller than those in the mural leaflet.
Tricuspid regurgitation (TR) is a progressive disease with high mortality and limited medical treatment options, and its association with atrial fibrillation (AF) has been documented. This study aimed to investigate whether successful rhythm control through catheter ablation for AF could reduce TR severity.
A total of 106 patients with drug-refractory AF with moderate to severe secondary TR who underwent AF ablation were screened from a single-centre ablation registry. Echocardiographic parameter changes (pre-procedure vs 1 day/1 year post-procedure) were analysed. Holter monitoring was performed at 3/6/12 months to assess AF recurrence. The primary outcome was at least one grade TR reduction with its main determinants evaluated.
After excluding 36 patients (prior tricuspid valve surgery, intracardiac devices or insufficient data), 70 patients (aged 63.8±9.7 years, 50% female) were analysed. Of these, 17 (24.3%) had severe TR, 55 (78.6%) persistent AF and all restored sinus rhythm with catheter ablation. The primary outcome was achieved in 53 (75.7%) at 1-year assessment (73.6% of moderate and 82.4% of severe TR). There were significant decreases of vena contracta (6.1->3.2 mm) and tricuspid annular diameter (37.3->32.6 mm) at 1 year. Although 25 patients experienced AF recurrence within 1 year, 56 (80%) patients finally maintained sinus rhythm with medical treatment (87% in patients with TR reduction and 59% without). From the multivariate analysis, sinus rhythm maintenance was the most significant determinant of TR reduction (OR 8.3, 95% CI 1.8 to 37.4).
In patients with AF with moderate to severe TR, more than two-thirds of patients experienced reduced TR severity, with notable improvements in echocardiographic parameters. Sinus rhythm maintenance was associated with significant TR reduction.
Learning objectives
To review the epidemiology, clinical presentation and diagnosis of mechanical complications of acute myocardial infarction including ventricular septal defect, free wall rupture and papillary muscle rupture. To discuss the existing data on outcomes of medical therapy, surgery and percutaneous intervention. To examine the limitations of currently available treatment modalities and need, as well as opportunity, for ongoing evolution and improvement of surgical and percutaneous therapies. To highlight the importance of the heart team in facilitating complex, shared decision making in treating these conditions which carry very high morbidity and mortality.
Major advances in reperfusion therapies after acute myocardial infarction (AMI) have resulted in dramatic reductions in the rate of mechanical complications including ventricular septal defect (VSD), free wall rupture (FWR) and papillary muscle rupture (PMR). However, the drastic decline in their incidence has not been accompanied by a...]]>