Complex diseases, such as coronary artery disease (CAD), are often multifactorial, caused by multiple underlying pathological mechanisms. Here, to study the multifactorial nature of CAD, we performed ...comprehensive clinical and multi-omic profiling, including serum metabolomics and gut microbiome data, for 199 patients with acute coronary syndrome (ACS) recruited from two major Israeli hospitals, and validated these results in a geographically distinct cohort. ACS patients had distinct serum metabolome and gut microbial signatures as compared with control individuals, and were depleted in a previously unknown bacterial species of the Clostridiaceae family. This bacterial species was associated with levels of multiple circulating metabolites in control individuals, several of which have previously been linked to an increased risk of CAD. Metabolic deviations in ACS patients were found to be person specific with respect to their potential genetic or environmental origin, and to correlate with clinical parameters and cardiovascular outcomes. Moreover, metabolic aberrations in ACS patients linked to microbiome and diet were also observed to a lesser extent in control individuals with metabolic impairment, suggesting the involvement of these aberrations in earlier dysmetabolic phases preceding clinically overt CAD. Finally, a metabolomics-based model of body mass index (BMI) trained on the non-ACS cohort predicted higher-than-actual BMI when applied to ACS patients, and the excess BMI predictions independently correlated with both diabetes mellitus (DM) and CAD severity, as defined by the number of vessels involved. These results highlight the utility of the serum metabolome in understanding the basis of risk-factor heterogeneity in CAD.
The extent of myocardial fibrosis in patients with severe aortic stenosis might have an important prognostic value. Non-invasive imaging to quantify myocardial fibrosis by measuring extracellular ...volume fraction might have an important clinical utility prior to aortic valve intervention.
Seventy-five consecutive patients with severe aortic stenosis, and 19 normal subjects were prospectively recruited and underwent pre- and post-contrast computed tomography for estimating myocardial extracellular volume fraction. Serum level of galectin-3 was measured and 2-dimensional echocardiography was performed to characterize the extent of cardiac damage using a recently published aortic stenosis staging classification.
Extracellular volume fraction was higher in patients with aortic stenosis compared to normal subjects (40.0±11% vs. 21.6±5.6%; respectively, p<0.001). In patients with aortic stenosis, extracellular volume fraction correlated with markers of left ventricular decompensation including New York Heart Association functional class, left atrial volume, staging classification of aortic stenosis and lower left ventricular ejection fraction. Out of 75 patients in the AS group, 49 underwent TAVI, 6 surgical AVR, 2 balloon valvuloplasty, and 18 did not undergo any type of intervention. At 12-months after aortic valve intervention, extracellular volume fraction predicted the combined outcomes of stroke and hospitalization for heart failure with an area under the curve of 0.77 (95% confidence interval: 0.65-0.88). A trend for correlation between serum galectin-3 and extracellular volume was noted.
In patients with severe aortic stenosis undergoing computed tomography before aortic valve intervention, quantification of extracellular volume fraction correlated with functional status and markers of left ventricular decompensation, and predicted the 12-months composite adverse clinical outcomes. Implementation of this novel technique might aid in the risk stratification process before aortic valve interventions.
While technological advances in the field of continuous‐flow left ventricular assist device (CF‐LVAD) are constantly being made, CF‐LVAD recipients are still subjected to a relatively high rate of ...LVAD‐related adverse events, with post‐LVAD gastrointestinal bleeding (GIB) being the most common one. GIB is associated with a significant impairment in quality of life, multiple hospital admissions, blood transfusion requirements and possibly death. Furthermore, of those patients who bled once, many will experience recurrent GIB events, which further aggravates their discomfort. While some medical and endoscopic treatment options are available, evidence regarding their benefit remains largely equivocal, with all related studies based on data from registries rather than clinical trials. Although having a major impact on LVAD recipients, an effective and validated pre‐implant screening options to predict GIB events post‐implant are scarce. This review focuses on the aetiology, incidence, risk factors, treatment options and the effect of new generation devices on post‐LVAD GIB.
Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment ...of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD) and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function.
To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes.
Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8%) and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs), their viability (measured by MTT assay), KLF-10 levels and angiogenic markers were evaluated after 1 week of culture.
In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol EPC CFUs: 1.25 (IQR 1.0-2.0) vs. 0.5 (IQR 0.5-1.9), p < 0.001; MTT:0.62 (IQR 0.44-0.93) vs. 0.52 (IQR 0.31-0.62), p = 0.001. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability MTT: 0.23 (IQR 0.11-0.46) vs. 0.19 (0.09-0.39), p = 0.04, but without differences in CFU count or angiopoietic markers.
In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.
Background Patients who have had an acute coronary syndrome ( ACS ) are at increased risk of recurrent cardiovascular events; however, paradoxically, high-risk patients who may derive the greatest ...benefit from guideline-recommended therapies are often undertreated. The aim of our study was to examine the management, clinical outcomes, and temporal trends of patients after ACS stratified by the Thrombolysis in Myocardial Infarction (TIMI) risk score for secondary prevention, a recently validated clinical tool that incorporates 9 clinical risk factors. Methods and Results Included were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys ( ACSIS ) between 2008 and 2016. Patients were stratified by the TIMI risk score for secondary prevention to low (score 0-1), intermediate (2), or high (≥3) risk. Clinical outcomes included 30-day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Of 6827 ACS patients enrolled, 35% were low risk, 27% were intermediate risk, and 38% were high risk. Compared with the other risk groups, high-risk patients were older, were more commonly female, and had more renal dysfunction and heart failure ( P<0.001 for each). High-risk patients were treated less commonly with guideline-recommended therapies during hospitalization (percutaneous coronary intervention) and at discharge (statins, dual-antiplatelet therapy, cardiac rehabilitation). Overall, high-risk patients had higher rates of 30-day major adverse cardiac events (7.2% low, 8.2% intermediate, and 15.1% high risk; P<0.001) and 1-year mortality (1.9%, 4.6%, and 15.8%, respectively; P<0.001). Over the past decade, utilization of guideline-recommended therapies has increased among all risk groups; however, the rate of 30-day major adverse cardiac events has significantly decreased among patients at high risk but not among patients at low and intermediate risk. Similarly, the 1-year mortality rate has decreased numerically only among high-risk patients. Conclusions Despite an improvement in the management of high-risk ACS patients, they are still undertreated with guideline-recommended therapies. Nevertheless, the outcome of high-risk patients after ACS has significantly improved in the past decade, thus they should not be denied these therapies.
ObjectiveSome patients following acute coronary syndrome (ACS) are at particularly increased risk for recurrent cardiovascular events. We aimed to examine temporal trends in the management and ...outcomes across the spectrum of these particularly high-risk patients.Design and settingA retrospective study based on the ACS Israeli survey (ACSIS) registry, a multicentre prospective national registry, taking place biennially in 25 cardiology departments in Israel. Temporal trends were examined in the early (2002–2008) and late (2010–2018) time periods.ParticipantsConsecutive patients with ACS enrolled in the ACSIS registry were stratified according to the Thrombolysis in Myocardial Infarction Risk Score for secondary prevention (TRS2°P) to high (TRS2°p=3), very high (TRS2°p=4) or extremely high risk (TRS2°p=5–9). Patients with TRS2°p<3 were excluded. From the initial 15 196 patients enrolled, 5359 patients were eventually included.Clinical outcome measures included 30-day major adverse cardiovascular events (MACE) and 1-year mortality.ResultsAmong 5359 patients (50% high risk, 30% very high risk and 20% extremely high risk), those with a higher risk were older, had more comorbidities, presented more with non-ST elevation myocardial infarction, and were treated less often with guideline-recommended pharmacotherapy and percutaneous coronary intervention. Over time, treatment has improved in all risk strata, and the rate of 30-day MACE has significantly decreased in all risk groups (from 21% to 10%, from 22% to 15%, and from 26% to 16%, in high, very high and extremely high-risk groups, respectively, p<0.001 for each). However, 1-year mortality decreased only among high and very high-risk patients, and not among extremely high-risk patients in whom 1-year mortality rates remained very high (28.7% vs 28.9%, p=1).ConclusionWithin a particularly high-risk cohort of patients with ACS, treatment has significantly progressed over almost 2 decades. While short-term outcomes have improved in all risk groups, 1-year mortality has remained unchanged in extremely high-risk patients with ACS.
Aims
Exercise games (exergames) have been recently proposed as a mode of facilitating physical activity in patients with chronic diseases. Although patients supported with left ventricular assist ...devices (LVADs) benefit from physical activity, specific LVAD‐related issues hinder their ability to exercise properly. The objective of this study was to assess the feasibility and safety of exergaming in LVAD‐supported patients.
Methods and results
Eleven LVAD‐supported patients were enrolled in a 4 week exergaming programme using Nintendo Wii console with five sport games. Patients were instructed to play for 30 min a day, 5 days a week. Data on exercise capacity and exergaming were collected by using the 6 min walk test (6MWT) and a daily self‐report diary, respectively. Feasibility of using the console and its safety was assessed by a semi‐structured patient interview. Quality of life was assessed by the Minnesota Living with Heart failure Questionnaire (MLHFQ) and the Cantril's Ladder of Life. Safety was assessed by patient's report in interview and diary. The study group consisted of 10 male patients and 1 female patient, mean age of 67 ± 7 years, of whom 10 were supported with the HeartMate 3 LVAD for a median of 10 (interquartile range 3, 21) months. Baseline exercise capacity assessed by the 6MWT ranged from 240 to 570 m (mean 448 ± 112). After 4 weeks of exergaming, 6MWT distance increased from a mean of 448 ± 112 (evaluated in six patients) to 472 ± 113 m (P = 0.023). Patients' Cantril's Ladder of Life score improved numerically from an average of 6.13 to 7.67, as did their MLHFQ score from 45.9 ± 27 to 38.7 ± 18, with higher and lower scores, respectively, reflecting higher quality of life. No specific LVAD‐related safety issues regarding exergaming were reported.
Conclusions
Exergaming was found to be a safe and feasible mode for encouraging physical activity in LVAD‐supported patients and carries a potential for improving exercise capacity and quality of life in these patients. Larger scale studies are warranted to further investigate the effect of exergaming in this patient population.
Aims
This study aimed to evaluate the different health‐related quality of life (HR‐QoL) aspects in patients with both short‐term and long‐term duration LVAD support at pre‐specified time intervals.
...Methods and results
We performed a single‐centre HR‐QoL analysis of short‐term and long‐term LVAD‐supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients' social and driving routines. Data were collected at baseline and at 6 or 12 month follow‐up. Included were 46 patients with a median time from LVAD implantation of 1.1 inter‐quartile range (IQR) 0.5, 2.6 years. The median KCCQ‐12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain 75 (IQR 50, 92) and worse scores in the physical limitation 42 (IQR 25, 75) and QoL 44 (IQR 25, 75) domains. No significant changes were apparent during study follow‐up KCCQ‐12 summary score 56 (IQR 35, 80), and no significant correlation between the KCCQ‐12 summary score and ventricular assist device‐support duration was detected (r = −0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy‐six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery.
Conclusions
Short‐term and long‐term LVAD‐supported patients had impaired HR‐QoL and sexual function at baseline and at follow‐up yet reported an improvement in social interactions and independency. A broader spectrum of patient's reported HR‐QoL measures should be integrated into the pre‐LVAD implantation assessment and preparation.
Although on election day each vote carries equal weight, in the U.S. there is a
strong correlation between policy and the preferences of the affluent, and a
weak correlation between policy and the ...preferences of the middle class or the
poor. This state of affairs can result from unequal input into the democratic
process. If a democracy allows unlimited private financing of political
campaigns, then prior to elections wealthy citizens or businesses can gain
greater influence than others on the political discourse. In addition, there is
a danger that elected representatives − who wish to be re-elected
− would decide in ways that serve the interests of their big donors. In
this article, I discuss an important aspect of money’s influence on
politics, namely whether corporations should be allowed to participate in the
financing of campaigns. This issue produced intense disagreement over the last
several years, following the U.S. Supreme Court decision which held that
restrictions against corporate campaign finance are unconstitutional since a
corporation’s right to freedom of political speech is no less than a
citizen’s right to freedom of political speech. Since in my opinion the
Court’s position is seriously mistaken, I find it important to look at
the arguments the Court provides and try to refute them.
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