Evaluation of left cardiac chamber function with cardiac magnetic resonance and association with outcome in patients with systemic sclerosis.

OBJECTIVE: This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc. METHODS: A total of 100 patients {54 [interquartile range (IQR) 46-64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality. RESULTS: The median LV GLS was -21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P = 0.049] was independently associated with New York Heart Association (NYHA) class II-IV heart failure symptoms. Over a median follow-up of 37 (21-62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement. CONCLUSION: In patients with SSc, LARS was independently associated with the presence of NYHA class II-IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc.

Innate immune cells in the pathophysiology of calcific aortic valve disease: lessons to be learned from atherosclerotic cardiovascular disease?

Calcific aortic valve disease (CAVD) is the most common valvular disease in the developed world with currently no effective pharmacological treatment available. CAVD results from a complex, multifactorial process, in which valvular inflammation and fibro-calcific remodelling lead to valve thickening and cardiac outflow obstruction. The exact underlying pathophysiology of CAVD is still not fully understood, yet the development of CAVD shows many similarities with the pathophysiology of atherosclerotic cardiovascular disease (ASCVD), such as coronary artery disease. Innate immune cells play a crucial role in ASCVD and might also play a pivotal role in the development of CAVD. This review summarizes the current knowledge on the role of innate immune cells, both in the circulation and in the aortic valve, in the development of CAVD and the similarities and differences with ASCVD. Trained immunity and clonal haematopoiesis of indeterminate potential are proposed as novel immunological mechanisms that possibly contribute to the pathophysiology of CAVD and new possible treatment targets are discussed.

Cardiac MRI to Visualize Myocardial Damage after ST-Segment Elevation Myocardial Infarction: A Review of Its Histologic Validation.

Cardiac MRI is a noninvasive diagnostic tool using nonionizing radiation that is widely used in patients with ST-segment elevation myocardial infarction (STEMI). Cardiac MRI depicts different prognosticating components of myocardial damage such as edema, intramyocardial hemorrhage (IMH), microvascular obstruction (MVO), and fibrosis. But how do cardiac MRI findings correlate to histologic findings? Shortly after STEMI, T2-weighted imaging and T2* mapping cardiac MRI depict, respectively, edema and IMH. The acute infarct size can be determined with late gadolinium enhancement (LGE) cardiac MRI. T2-weighted MRI should not be used for area-at-risk delineation because T2 values change dynamically over the first few days after STEMI and the severity of T2 abnormalities can be modulated with treatment. Furthermore, LGE cardiac MRI is the most accurate method to visualize MVO, which is characterized by hemorrhage, microvascular injury, and necrosis in histologic samples. In the chronic setting post-STEMI, LGE cardiac MRI is best used to detect replacement fibrosis (ie, final infarct size after injury healing). Finally, native T1 mapping has recently emerged as a contrast material-free method to measure infarct size that, however, remains inferior to LGE cardiac MRI. Especially LGE cardiac MRI-defined infarct size and the presence and extent of MVO may be used to monitor the effect of new therapeutic interventions in the treatment of reperfusion injury and infarct size reduction. © RSNA, 2021 Online supplemental material is available for this article.

Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease.

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death globally. Inflammation is an important driver of CVD where tissue damage may lead to the formation of deadly thrombi. Therefore, antithrombotic drugs, such as platelet inhibitors, are crucial for secondary risk prevention in coronary artery disease (CAD) and peripheral artery disease (PAD). For severe forms of the disease, dual-pathway inhibition (DPI) where low-dose aspirin is combined with rivaroxaban has shown improved efficacy in reducing cardiovascular mortality. METHODS: Given this greater improvement in mortality, and the importance of inflammation in driving atherosclerosis, the potential for off-target inflammation-lowering effects of these drugs was evaluated by looking at the change in immune cell distribution and responsiveness to ex vivo lipopolysaccharide (LPS) stimulation after 3 months of DPI in patients with CAD. RESULTS: We observed no changes in whole blood or peripheral blood mononuclear cell (PBMC) immune cell responsiveness to LPS after 3 months of DPI. Additionally, we did not observe any changes in the distribution of total white blood cells, monocytes, neutrophils, lymphocytes, or platelets during the study course. Signs of systemic inflammation were studied using Olink proteomics in 33 patients with PAD after 3 months of DPI. No changes were observed in any of the inflammatory proteins measured after the treatment period, suggesting that the state of chronic inflammation was not altered in these subjects. CONCLUSION: Three months of DPI does not result in any meaningful change in immune cell responsiveness and distribution in patients with CAD or PAD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05210725.

Paravalvular regurgitation after transcatheter aortic valve replacement: incidence, quantification, and prognostic impact.

Transcatheter aortic valve replacement (TAVR) is the standard of care in aortic stenosis with results comparable to surgical aortic valve replacement. However, paravalvular regurgitation (PVR) is more common after TAVR. With the alteration of devices and implantation techniques, the incidence of moderate or more PVR has declined. Mild PVR is still common in around 30% of TAVR patients in low-risk trials. Progression of AS causes myocardial hypertrophy and varying degrees of diastolic dysfunction which may cause heart failure even in combination with small volumes of PVR. Any degree of PVR is associated with an increased risk of overall and cardiovascular mortality. Predictors of PVR are annular eccentricity, severe calcification of the aortic valve, bicuspid aortic valves, and type of prosthesis where balloon-expandable devices are associated with less PVR. PVR is diagnosed using echocardiography, aortic angiogram with or without videodensitometry, haemodynamic parameters, or cardiac magnetic resonance. PVR can be treated using post-dilation, interventional treatment using a vascular plug, or implantation of a second device. Successful post-dilation depends on balloon size which should at least be equal to or >95% of the mean annulus diameter. Implantation of a second device to reduce PVR is successful in ∼90% of cases, either through lengthening of the sealing skirt in case of inadequate position or through further expansion of the index device. Implantation of a vascular plug can successfully reduce PVR and reduce mortality.

Assessment of paravalvular regurgitation after transcatheter aortic valve replacement using 2D multi-velocity encoding and 4D flow cardiac magnetic resonance.

AIMS: To compare the novel 2D multi-velocity encoding (venc) and 4D flow acquisitions with the standard 2D flow acquisition for the assessment of paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR) using cardiac magnetic resonance (CMR)-derived regurgitant fraction (RF). METHODS AND RESULTS: In this prospective study, patients underwent CMR 1 month after TAVR for the assessment of PVR, for which 2D multi-venc and 4D flow were used, in addition to standard 2D flow. Scatterplots and Bland-Altman plots were used to assess correlation and visualize agreement between techniques. Reproducibility of measurements was assessed with intraclass correlation coefficients. The study included 21 patients (mean age ± SD 80 ± 5 years, 9 men). The mean RF was 11.7 ± 10.0% when standard 2D flow was used, 10.6 ± 7.0% when 2D multi-venc flow was used, and 9.6 ± 7.3% when 4D flow was used. There was a very strong correlation between the RFs assessed with 2D multi-venc and standard 2D flow (r = 0.88, P < 0.001), and a strong correlation between the RFs assessed with 4D flow and standard 2D flow (r = 0.74, P < 0.001). Bland-Altman plots revealed no substantial bias between the RFs (2D multi-venc: 1.3%; 4D flow: 0.3%). Intra-observer and inter-observer reproducibility for 2D multi-venc flow were 0.98 and 0.97, respectively, and 0.92 and 0.90 for 4D flow, respectively. CONCLUSION: Two-dimensional multi-venc and 4D flow produce an accurate quantification of PVR after TAVR. The fast acquisition of the 2D multi-venc sequence and the free-breathing acquisition with retrospective plane selection of the 4D flow sequence provide useful advantages in clinical practice, especially in the frail TAVR population.

Cardiovascular imaging research and innovation in 2023.

In 2023, cardiovascular imaging has made significant advancements, in terms of technology, pathophysiology, and clinical application. In this review, the most recent research findings in the field of cardiovascular imaging are discussed. Artificial intelligence and large population cohorts, together with several technical improvements, have had a crucial impact on the technological advancements of echocardiography, cardiovascular magnetic resonance, computed tomography (CT), and nuclear medicine. In the field of ischaemic heart disease, it has been demonstrated that appropriate non-invasive imaging strategies improve patients' management and reduce invasive procedures and the need for additional testing at follow-up. Moreover, improvements in plaque characterization with CT are an expanding field of research with relevant implications for the prediction of disease severity, evolution, and response to treatment. In the field of valvular heart disease, imaging techniques have advanced alongside improvements in transcatheter treatment for aortic stenosis, mitral, and tricuspid regurgitation. Finally, in the field of heart failure and cardiomyopathies, cardiovascular imaging has reinforced its crucial role in early diagnosis and risk evaluation, showcasing advanced techniques that outperform traditional methods in predicting adverse outcomes.

Peripheral microvascular function is linked to cardiac involvement on cardiovascular magnetic resonance in systemic sclerosis-related pulmonary arterial hypertension.

AIMS: Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). METHODS AND RESULTS: Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). CONCLUSION: SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.

Invasive coronary imaging of inflammation to further characterize high-risk lesions: what options do we have?

Coronary atherosclerosis remains a leading cause of morbidity and mortality worldwide. The underlying pathophysiology includes a complex interplay of endothelial dysfunction, lipid accumulation and inflammatory pathways. Multiple structural and inflammatory features of the atherosclerotic lesions have become targets to identify high-risk lesions. Various intracoronary imaging devices have been developed to assess the morphological, biocompositional and molecular profile of the intracoronary atheromata. These techniques guide interventional and therapeutical management and allow the identification and stratification of atherosclerotic lesions. We sought to provide an overview of the inflammatory pathobiology of atherosclerosis, distinct high-risk plaque features and the ability to visualize this process with contemporary intracoronary imaging techniques.

Metformin therapy in diabetes: the role of cardioprotection.

In patients with diabetes mellitus, the incidence of cardiovascular disease is increased, and the outcome following cardiovascular events is worse. The antihyperglycemic drug metformin appears to limit cardiovascular death in patients with type 2 diabetes. Indeed, preclinical studies have demonstrated that metformin limits (myocardial) ischemia and reperfusion injury, independent from its glucose-lowering effect. This cardioprotection is mediated by activation of the Reperfusion Injury Salvage Kinase (RISK) pathway, activation of AMPK and by an increased formation of adenosine. In addition, metformin can modulate several cardiovascular risk factors and reduces the development of heart failure in murine models. Consequently, treatment with metformin might potentially improve cardiovascular outcome in patients at risk for myocardial ischemia, even if these patients do not have diabetes. In the current paper, we focus on the direct cardioprotective actions of metformin and the mechanisms that underlie these effects.

Future steps in cardio-oncology-a national multidisciplinary survey among healthcare professionals in the Netherlands.

BACKGROUND: The awareness of cancer therapy-related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice. MATERIAL AND METHODS: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media. RESULTS: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms' cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic. CONCLUSION: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients.

Effect of ticagrelor and prasugrel on remote myocardial inflammation in patients with acute myocardial infarction with ST-elevation: a CMR T1 and T2 mapping study.

PURPOSE: Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium. METHODS: Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2-7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging. RESULTS: After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4-950.4] ms for ticagrelor vs. 932.6 [915.5-949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups. CONCLUSION: In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping.

Assessing the Novel Myval Balloon-Expandable Valve with the Evolut Valve: A Propensity-Matched Study.

BACKGROUND: The Myval balloon-expandable (BE) valve has shown encouraging early clinical data in terms of safety and efficacy. Comparative data with other well-established contemporary valves are nonetheless still scarce. This study aims to compare the performance of the Myval BE valve with the Evolut self-expanding (SE) valve. METHODS: In this retrospective single-center study, 223 patients with symptomatic severe aortic stenosis (AS) were included and treated with the Myval BE valve (n = 120) or with the Evolut SE valve (n = 103). Then, 91 pairs were compared after matching. Clinical outcomes were evaluated at 30 days and 1 year. Echocardiographic follow-up was performed at 30 days. RESULTS: Procedural complications were rare in both groups. At the 30-day follow-up, no significant difference in cardiac death (Myval: 1% vs. Evolut: 2%, p = 0.56), stroke (2% vs. 4%, p = 0.41) and myocardial infarction (1% vs. 3%, p = 0.31) was observed. A permanent pacemaker implantation (PPI) was significantly less needed in the Myval group (4% vs. 15%, p = 0.01). At 1 year, cardiac death (2% vs. 4%, p = 0.41) and the stroke rate (7% vs. 5%, p = 0.76) were similar. Moderate-severe paravalvular leakage (PVL) was also comparable in both groups (1% vs. 4%, p = 0.17). CONCLUSION: Safety and efficacy outcomes were comparable between the two valves, except for a higher PPI rate for the Evolut SE valve. Up to 1-year follow-up, clinical outcomes showed acceptable rates of stroke and cardiac death with both valves. Valve hemodynamics were excellent with a low rate of moderate-severe PVL in both groups.

Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors.

An increasing number of patients develop an atherothrombotic myocardial infarction (MI) in the absence of standard modifiable risk factors (SMuRFs). Monocytes and macrophages regulate the development of atherosclerosis, and monocytes can adopt a long-term hyperinflammatory phenotype by epigenetic reprogramming, which can contribute to atherogenesis (called "trained immunity"). We assessed circulating monocyte phenotype and function and specific histone marks associated with trained immunity in SMuRFless patients with MI and matched healthy controls. Even in the absence of systemic inflammation, monocytes from SMuRFless patients with MI had an increased overall cytokine production capacity, with the strongest difference for LPS-induced interleukin-10 production, which was associated with an enrichment of the permissive histone marker H3K4me3 at the promoter region. Considering the lack of intervenable risk factors in these patients, trained immunity could be a promising target for future therapy.

Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial.

BACKGROUND: Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial. METHODS: Patients with chronic coronary disease were randomly allocated to colchicine 0.5 mg once daily or placebo on a background of optimal medical therapy. Cause-specific mortality data were analysed, stratified by treatment status. Multivariate analyses were performed to examine the predictors of mortality as well as cardiovascular and non-cardiovascular death. RESULTS: After a median 28.6 months follow-up, 133 out of 5522 participants (2.4%) died. Forty-five deaths were cardiovascular (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], HR, 0.80; 95% CI, 0.44-1.44), while eighty-eight deaths were non-cardiovascular (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99-2.31). Forty-eight deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), thirteen end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), eight infection (4 [0.1%] versus 4 [0.1%]), five dementia (4 [0.1%] versus 1 [0.0%]) and five related multiple organ failure (3 [0.1%] versus 2 [0.1%]). Multivariable analysis demonstrated age > 65 years was the only independent baseline characteristic associated with non-cardiovascular death (HR, 3.65; 95% CI, 2.06-6.47). CONCLUSIONS: During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on any specific causes of death. Most deaths were related to non-cardiovascular causes, underscoring the importance of comorbidities as drivers of all-cause mortality in patients with chronic coronary disease.

Diastolic delta best predicts paravalvular regurgitation after transcatheter aortic valve replacement as assessed by cardiac magnetic resonance: the APPOSE trial.

AIMS: Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement (TAVR) that poses an increased risk of rehospitalization for heart failure and mortality. The aim of this study was to assess the accuracy of haemodynamic indices to predict relevant PVR. METHODS AND RESULTS: In this prospective single-centre clinical trial, four haemodynamic indices of PVR measured during TAVR were assessed for their correlation with gold standard cardiac magnetic resonance (CMR)-derived regurgitant fraction (CMR-RF) at 1 month follow-up: diastolic delta (DD), heart rate-adjusted diastolic delta (HR-DD), aortic regurgitation index (ARI), and aortic regurgitation index ratio (ARI ratio). These haemodynamic indices were analysed for their ability to predict relevant PVR (defined as CMR-RF > 20%) using receiver operating characteristic (ROC) curves with corresponding area under the ROC curves (AUCs). A total of 77 patients were included and had CMR performed 41 ± 14 days after TAVR. Mean CMR-RF was 12.4 ± 9.3%. Fifteen (19.5%) patients had CMR-RF > 20%. DD had the best correlation with CMR-RF and the highest AUC to predict relevant PVR (0.82; 95% CI, 0.72-0.92), followed by HR-DD (AUC 0.78; 95% CI, 0.67-0.89), ARI (AUC 0.78; 95% CI, 0.66-0.89), and ARI ratio (AUC 0.65; 95% CI, 0.49-0.81). The optimal cut-off value for DD was 32 mmHg, with sensitivity of 69% and specificity of 77% in predicting relevant PVR. CONCLUSION: DD measured during TAVR best predicts relevant PVR. Correction for heart rate (HR-DD) or systolic blood pressure (ARI, ARI ratio) did not improve this predictive value.

Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.

Introduction: Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM). Methods: The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model. Results: A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes (pinteraction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10). Discussion: In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.

The cardioprotective effects of metformin.

PURPOSE OF REVIEW: In patients with type 2 diabetes mellitus, treatment with metformin is associated with a lower cardiovascular morbidity and mortality, compared with alternative glucose-lowering drugs. It has been suggested that metformin might exert direct protective effects on the heart. RECENT FINDINGS: This review appraises recent experimental animal studies on the effect of metformin on myocardial ischaemia-reperfusion injury and remodeling. In murine models of myocardial infarction, the administration of metformin potently limits infarct size. Activation of adenosine monophosphate-activated protein kinase, increased formation of adenosine, and the prevention of opening of the mitochondrial permeability transition pore at reperfusion all contribute to this cardioprotective effect. In addition, metformin therapy attenuates postinfarction cardiac remodeling. There is evidence that activation of adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase, and a reduced collagen expression are crucial for this effect. SUMMARY: The finding that metformin limits myocardial infarct size and remodeling in animal models of myocardial infarction suggests that patients suffering from myocardial ischaemia could benefit from treatment with metformin, even when these patients do not have diabetes. Currently, several clinical trials are being performed to test this hypothesis.

Psychological distress is independently related to new coronary events at 8 years' follow-up in elderly primary care patients with hypertension.

OBJECTIVE: Occurrence of psychological distress in hypertensive patients could have a negative synergistic effect on future cardiovascular events (CVEs). The aim of this study was to determine the association between anxiety or depressive symptoms in elderly hypertensive primary care patients and the development of new CVEs and all-cause mortality. METHODS: A prospective cohort study was conducted in five Dutch general practices between June 2010 and January 2012. Patients with primary care managed hypertension, aged 60-85 years, were included and completed the GAD-7 and PHQ-9, measuring anxiety and depressive symptoms respectively. The incidence of new CVEs (coronary event, cerebrovascular disease, atrial fibrillation and heart failure) and all-cause mortality at 8 years' follow-up was recorded by data extraction of the digital information systems. RESULTS: Among the 555 included participants (mean age 70 ± 6.6 years; 56% female), 29 (5.2%) had a new coronary event, 42 (7.6%) a cerebrovascular disease, 57 (10.3%) atrial fibrillation, 22 (4%) heart failure and 68 (12.3%) died. Elevated anxiety and depression scores increased the risk of a coronary event independently and significantly by 12% (HR 1.12; 95% CI [1.04-1.22], p = 0.005) and 18% (HR 1.18; 95% CI [1.08-1.28], p < 0.0001), respectively, adjusted for relevant (Framingham) baseline covariates. No associations were found with regard to other CVEs and all-cause mortality. CONCLUSION: In a random sample of elderly primary care hypertension patients there was a significant association between psychological distress and the occurrence of new coronary events after 8 years' follow-up but not with other CVEs and all-cause mortality.