Repurposing Colchicine for Heart Disease.

Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed.

Inflammation in heart failure: pathophysiology and therapeutic strategies.

A role for inflammation in the development and progression of heart failure (HF) has been proposed for decades. Multiple studies have demonstrated the potential involvement of several groups of cytokines and chemokines in acute and chronic HF, though targeting these pathways in early therapeutic trials have produced mixed results. These studies served to highlight the complexity and nuances of how pro-inflammatory pathways contribute to the pathogenesis of HF. More recent investigations have highlighted how inflammation may play distinct roles based on HF syndrome phenotypes, findings that may guide the development of novel therapies. In this review, we propose a contemporary update on the role of inflammation mediated by the innate and adaptive immune systems with HF, highlighting differences that exist across the ejection fraction spectrum. This will specifically be looked at through the lens of established and novel biomarkers of inflammation. Subsequently, we review how improvements in inflammatory pathways may mediate clinical benefits of existing guideline-directed medical therapies for HF, as well as future therapies in the pipeline targeting HF and inflammation.

Videoconference version of the Montreal Cognitive Assessment: normative data for Quebec-French people aged 50 years and older.

BACKGROUND: The COVID-19 pandemic forced health professionals to rapidly develop and implement telepractice and remote assessments. Recent reviews appear to confirm the validity of a wide range of neuropsychological tests for teleneuropsychology and among these, the Montreal Cognitive Assessment (MoCA), a cognitive screening test widely used in clinical settings. The normative data specific to the context of videoconference administration is essential, particularly that consider sociodemographic characteristics. AIMS: This study had for objective to develop French-Quebec normative data for videoconference-administration of the MoCA that consider sociodemographic characteristics. METHODS: A total of 230 community-dwelling adults aged 50 years and older taking part in clinical trials completed the MoCA by videoconference. Regression analyses were run with sex, education, and age as predictors of the total MoCA scores, based on previously published norms. As an exploratory analysis, a second regression analysis was also run with cardiovascular disease as a predictor. RESULTS: Regression analyses revealed that older age and lower education were associated with poorer total MoCA scores, for medium effect size (p < 0.001, R2 = 0.17). Neither sex nor cardiovascular disease, were significant predictors in our analyses. For clinicians, a regression equation was proposed to calculate Z scores. DISCUSSION: This study provides normative data for the MoCA administered via videoconference in Quebec-French individuals aged 50 years and over. CONCLUSIONS: The present normative data will not only allow clinicians to continue to perform assessments remotely in this pandemic period but will also allow them to perform cognitive assessments to patients located in remote areas.

Colchicine in the Management of Acute and Chronic Coronary Artery Disease.

PURPOSE OF REVIEW: Inflammation is involved in the initiation, progression, and destabilization of atherosclerosis. Anti-inflammatory strategies aimed at reducing residual cardiovascular (CV) risk have gained increasing interest in addition to the traditional management of risk factors. Colchicine is a potent anti-inflammatory therapy that affects the inflammasome and other targets. We will herein review the most recent evidence regarding the usefulness of colchicine in patients with coronary artery disease (CAD). RECENT FINDINGS: Colchicine has recently been repurposed from its traditional use to a number of CV indications. The landmark COLCOT and LoDoCo2 trials have demonstrated that long-term use of colchicine was associated with a reduced rate of CV events in both acute and chronic presentations of CAD, with an overall good safety profile. Colchicine is emerging as a valuable, safe, and cost-effective therapy in addition to standard of care for the prevention of atherothrombotic events in CAD.

Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

AIMS: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. METHODS AND RESULTS: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4-7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). CONCLUSION: Patients benefit from early, in-hospital initiation of colchicine after MI. TRIAL REGISTRATION: COLCOT ClinicalTrials.gov number, NCT02551094.

Lymphocytopenia During Hospitalization for Acute Heart Failure and Its Relationship With Portal Congestion and Right Ventricular Function.

BACKGROUND: Lymphocytopenia is associated with mortality in acute heart failure (AHF), and portal congestion has been suggested to play a role in leukocyte distribution. The associations between lymphocytopenia and ultrasound surrogates for portal congestion have never been studied. We aimed to characterize the determinants of lymphocytopenia, explore the associations between lymphocytopenia and portal congestion, and explore the relationships between lymphocytopenia and outcomes in AHF. METHODS AND RESULTS: Patients were compared according to tertiles of lymphocyte count (very low, <0.87 × 109/L; low, 0.87-1.2 × 109/L; or normal, >1.2 × 109/L). One hundred three patients with AHF were prospectively assessed at baseline and discharge. At baseline, 69% of patients had a lymphocyte count below the normal range. Patients with baseline very low lymphocyte count were older, had more advanced disease and higher portal vein pulsatility index when compared with those in the higher tertiles. Very low lymphocyte count at baseline was associated with age (odds ratio (OR) 1.098), portal vein pulsatility index (OR, 1.026), and tricuspid annular plane systolic excursion (OR, 0.865, all P < .05). The portal vein pulsatility index was the most powerful determinant of lymphocytopenia at discharge (OR 1.033, P < .05). In a Cox model, lymphocytopenia at discharge was associated with mortality (hazard ratio 4.796, P < .05). CONCLUSIONS: In AHF, lymphocytopenia is associated with ultrasound surrogates for portal congestion and right ventricular dysfunction. Whether these associations depict a potent pathophysiologic pathway or whether they only reflect a more advanced disease remains uncertain.

A Practical Approach to Cerebro-Somatic Near-Infrared Spectroscopy and Whole-Body Ultrasound.

Near-infrared spectroscopy (NIRS) is an emerging noninvasive monitoring modality based on chromophore absorption of infrared light. Because NIRS provides instantaneous information on cerebral and somatic tissue oxygenation, it becomes mandatory to identify rapidly the etiology of impaired regional oxygenation and thus perfusion. To do so, the use of whole-body ultrasound (WHOBUS) represents a significant advance in the management of patients experiencing cerebral or somatic desaturation. This narrative review describes the authors' experience since 2002 in the use of combined NIRS and WHOBUS. A practical approach in the use of both modalities and their respective limitations is described.

Impact of Intubation Time on Survival following Coronary Artery Bypass Grafting: Insights from the Surgical Treatment for Ischemic Heart Failure (STICH) Trial.

OBJECTIVE: The authors aimed to assess determinants of intubation time and evaluate its impact on 30-day and 1-year postoperative survival in Surgical Treatment for Ischemic Heart Failure (STICH) trial patients. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A multivariable Cox proportional hazards model was used among the 1,446 surgical patients from the STICH trial who survived 36 hours after operation, in order to identify perioperative factors associated with 30-day and 1-year postoperative mortality. A multivariable logistic regression model was used to determine risk factors associated with intubation time. MEASUREMENTS AND MAIN RESULTS: At 36 hours post-operation, 1,298 (out of 1,446) were extubated and 148 (10.2%) still intubated. Median postoperative intubation time was 11.4 hours. Among patients surviving 36 hours, a multivariable model was developed to predict 30-day (c-index = 0.88) and 1-year (c-index = 0.78) mortality. Intubation time was the strongest independent predictor of 30-day (hazard ratio [HR] 5.50) and 1-year mortality (HR 3.69). Predictors of intubation time >36 hours included mitral valve procedure, New York Heart Association class, left ventricular systolic volume index, creatinine, previous coronary artery bypass grafting (CABG), and age. Results were similar in patients surviving 24 hours post-operation, where intubation time was also the strongest predictor of 30-day (HR 4.18, c-index 0.87) and 1-year (HR 2.81, c-index 0.78) mortality. CONCLUSIONS: Intubation time is the strongest predictor of 30-day and 1-year mortality among patients with ischemic heart failure undergoing CABG. Combining intubation time with other mortality risk factors may allow the identification of patients at the highest risk for whom the development of specific strategies may improve outcomes.

Setting Up a Heart Failure Program in 2018: Moving Towards New Paradigm(s).

PURPOSE OF REVIEW: Heart failure (HF) is the first cause of hospitalization in the elderly in Western countries, generating tremendous healthcare costs. Despite the spread of multidisciplinary post-discharge programs, readmission rates have remained unchanged over time. We review the recent developments in this setting. RECENT FINDINGS: Recent data plead for global reorganization of HF care, specifically targeting patients at high risk for further readmission, as well as a stronger involvement of primary care providers (PCP) in patients' care plan. Besides, tools, devices, and new interdisciplinary expertise have emerged to support and be integrated into those programs; they have been greeted with great enthusiasm, but their routine applicability remains to be determined. HF programs in 2018 should focus on pragmatic assessments of patients that will benefit the most from the multidisciplinary care; delegating the management of low-risk patients to trained PCP and empowering the patient himself, using the newly available tools as needed.

Refractory cardiac arrest, inferior vena cava agenesis and extracorporeal cardiopulmonary resuscitation: a demanding combination.

Inferior vena cava abnormalities or agenesis had to be suspected in front of technical difficulties during venous catheterization. In the setting of extracorporeal life support and during chest compressions, femoral vascular access is the easiest, most efficient and, perhaps, the first approach for a successful extracorporeal cardiopulmonary resuscitation. In the case of inferior vena cava agenesis leading to cannulation failure and/or complications, the use of the right internal jugular vein for salvage venous cannulation is a potential life-saving strategy.

Vascular and Microvascular Endothelial Function in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Assessment of vascular endothelial function lacks consistency, and microvascular endothelial function has been only partly assessed in heart failure with preserved ejection fraction (HFpEF). METHODS: The study population consisted of 90 patients: 45 had well documented HFpEF, and 45 had hypertension and no history or evidence of heart failure. Patients with hypertension but no heart failure were matched with HFpEF patients for age, sex, and diabetes. They served as control subjects. All patients underwent 2-dimensional Doppler echocardiography and vascular function measurements, including assessment of arterial wave reflections and arterial stiffness, brachial artery flow-mediated dilation (FMD), and forearm cutaneous blood flow with the use of a laser Doppler flow probe at rest and after release of arterial occlusion for 5 minutes. RESULTS: Brachial artery FMD was lower in HFpEF than in control subjects (median (IQR) 3.6 (0.4-7.4) vs. 7.2 (3.2-17.2)%, P = .001). Forearm cutaneous blood flow at rest was similar in HFpEF and control subjects (P = .68). After release of arterial occlusion, forearm cutaneous peak blood flow was lower in HFpEF than in control subjects (P = .03). Estimated aortic systolic and mean blood pressures were similar in HFpEF and control subjects, whereas pulse pressure and pressure augmentation were greater in HFPEF than in control subjects (both P < .05). CONCLUSION: Compared with hypertensive control subjects, patients with HFpEF had a depressed endothelial function in the forearm vasculature and microvasculature.

Cardiogenic shock, asthma, and hypereosinophilia.

Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss) is a multisystem syndrome associating asthma, hypereosinophilia,and signs of peripheral vasculitis. We report the case of a 21-year-old man admitted for cardiogenic shock revealing a severe left and right ventricular dysfunction. Hypereosinophilia, history of asthma, and peripheral neuropathy strongly suggested the diagnosis of EGPA. Cardiac magnetic resonance imaging confirmed heart involvement with a diffuse subendocardial late gadolinium enhancement. The patient was successfully treated with systemic corticosteroids, intravenous cyclophosphamide, and inotropes. At 6-month follow-up, the patient is doing well. Cardiac involvement is rare in EGPA and often carries poor prognosis. Specific early steroid therapy may improve hemodynamic at short term, allowing postponing the need for circulatory mechanical support or heart transplantation.

Management of cardiogenic shock: a narrative review.

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

Low-Dose Colchicine in Patients With Type 2 Diabetes and Recent Myocardial Infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44-0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention.

Dynamic nature of pulmonary artery systolic pressure in decompensated heart failure with preserved ejection fraction: role of functional mitral regurgitation.

BACKGROUND: Pulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary artery systolic pressure (PASP) and functional mitral regurgitation (FMR). METHODS AND RESULTS: Two-dimensional Doppler echocardiography was prospectively performed before initiation of standard therapy and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for non-HFpEF-related dyspnea. Left atrial volume index, and E/e' ratio, and PASP were significantly greater and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the 37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the 11 HFpEF patients who did not (-24 vs -9 mm Hg, respectively; P < .0001), whereas PASP remained unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e' ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation between PASP and mitral EROA was the only one that remained significant by multivariate analysis. CONCLUSIONS: Noninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR.

Acute myocardial infarction with normal coronary arteries associated with subclinical Graves disease.

Myocardial infarction occurring with angiographically normal coronary arteries is rare and often described in young people. This report describes a case of myocardial infarction with normal coronary arteries in a young female patient related to coronary thrombosis complicated by left ventricular apical thrombus in the setting of an unknown and subclinical Graves disease.

Extracorporeal membrane oxygenation and microaxial left ventricular assist device in cardiogenic shock: Choosing the right mechanical circulatory support to improve outcomes.

Objective: To evaluate the outcomes of patients supported with Impella (CP/5.0) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock according to shock phenotype. The primary end point was 30-day survival. Methods: A retrospective study of patients supported with Impella (CP/5.0) or VA-ECMO between 2010 and 2020 was performed. Patients were grouped according to 1 of 2 shock phenotypes: isolated left ventricular (LV) dysfunction versus biventricular dysfunction or multiple organ failure (MOF). The local practice favors Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF. Results: Among the 75 patients included, 17 (23%) had isolated LV dysfunction. Patients with biventricular dysfunction or MOF had a greater median lactate level compared with those with isolated LV dysfunction (7.9 [2.9-11.8] vs 3.8 [1.1-5.8] mmol/L, respectively). Among patients with isolated LV dysfunction, 30-day survival was 46% for the Impella group (n = 13) and 75% for VA-ECMO (n = 4). Among patients with biventricular dysfunction or MOF, 30-day survival was 9% for the Impella group (n = 11) and 28% for VA-ECMO (n = 47). Patients supported with Impella 5.0 had better 30-day survival compared with those supported with Impella CP, for both shock phenotypes (83% vs 14% and 14% vs 0%, respectively). Conclusions: In this small cohort, patients supported with Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF had acceptable survival at 30 days. Patients with biventricular dysfunction or MOF who were supported by Impella had the lowest survival rates. Patients with isolated LV dysfunction who were supported with VA-ECMO had good 30-day survival.

Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.

AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.