Tag Archives: #cardiac

Weight-loss Treatment Prevents Accumulation of Lipid Linked to Cardiac Mortality (Medicine)

Researchers at the Karolinska Institutet, University of Oxford and University of Copenhagen have shown that elevated levels of lipids known as ceramides can be associated with a ten-fold higher risk of death from cardiovascular disease. Treatment with liraglutide could keep the ceramide levels in check, compared with placebo. The results have been published in the Journal of the American College of Cardiology.

Approximately 16 percent of the Swedish population suffers from obesity (BMI over 30), which is one of the greatest risk factors for cardiovascular diseases such as myocardial infarction and stroke. The World Health Organisation (WHO) estimates that cardiovascular diseases are the main cause of mortality worldwide, with more than 17 million deaths a year.

“Understanding the link between obesity and cardiovascular diseases is important and can lead the way to the development of new therapies,” says principal investigator docent Craig Wheelock at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.

Fat has traditionally been seen as simply storage tissue, but in recent years it has been shown to be a ‘biochemical laboratory’ capable of producing signalling molecules that exert potent biological functions. Understanding how adipocytes produce and release these molecules opens the possibility of reprogramming them with the aim of preventing future incidence of cardiovascular disease.

Applying a mass-spectrometry method called metabolomics, the Wheelock Laboratory was able to measure levels of multiple metabolites secreted by two kinds of human fat tissue.

Antonio Checa, researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. © Marc Mateos

The fat that accumulates around the heart in obese individuals secreted different metabolites relative to subcutaneous fat. Notably, thoracic adipose tissue (which surrounds the heart) from obese individuals secreted higher levels of ceramides, a kind of lipid that belongs to the sphingolipid family. In particular, elevated levels were observed of a lipid variant called C16:0-ceramide, which is based on palmitic acid – a saturated fat consisting of 16 carbon atoms. Ceramides are found in high levels in cell membranes and are also important signalling molecules.

The researchers were also able to show that ceramides secreted from adipose tissue damaged human blood vessels by initiating a process called oxidative stress, which can eventually lead to heart attacks and stroke.

“These results show emphatically that fat is not just energy-storage tissue but also a source of important bioactive molecules that can have powerful immunomodulatory functions,” Wheelock says. “In addition, all tissue is not equal, and the type of fat is clearly important in determining the observed biological function.”

To understand the significance of the cardiovascular effects of the ceramides, the researchers studied 633 patients with atherosclerosis, who were monitored for more than five years. They found that elevated levels of both C16:0-ceramide and its glycosylated variant could be linked to a ten-fold increase in the risk of fatal cardiovascular disease, even after controlling for other risk factors including age and weight. The results were consistent with earlier studies by other research groups.

“The results suggest that it could be worth incorporating the measurement of different kinds of sphingolipids, both in their original form as well as the glycosylated variants, to better gauge the risk of the occurrence of a fatal cardiovascular event,” says co-author Antonio Checa, researcher at Karolinska Institutet who developed the sphingolipid platform and conducted the analyses.

Professor Charalambos Antoniades at the University of Oxford. © Oxford Medical Illustrations at the John Radcliffe Hospital

The results also gave the researchers reason to examine if high ceramide levels in the blood can be effectively reduced. In the last part of the study, 32 volunteers were placed on a low-calorie diet for eight weeks before being split into two groups, one that received a placebo and one that received liraglutide, a GLP 1-analogue drug that is approved for the treatment of obesity and type 2 diabetes. Both groups continued the low-calorie diet for another 44 weeks. One year after the study onset, ceramide levels in the blood had increased significantly in the control group, while levels remained stable in the liraglutide group.

“The most important findings are that we add to the evidence that there is a direct correlation between risk of fatal cardiovascular disease and ceramide levels in the blood, and that this can be treated with an existing medication,” Wheelock says.

The study was led and coordinated by Professor Charalambos Antoniades at the University of Oxford.

“We reveal for the first time the role that the ceramides play as messengers that bring about the damaging effect on blood vessels that we see in obesity,” Charalambos Antoniades says. “This presents unique opportunities for the improved diagnosis and treatment of cardiovascular disease.”

The study was financed by the Swedish Heart and Lung Foundation, the Novo Nordisk Foundation and the British Heart Foundation.

Featured image: Craig Wheelock, docent Department of Medical Biochemistry and Biophysics, Karolinska Institutet © Ola Hedin


Publication: “Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease,” Nadia Akawi, Antonio Checa, Alexios S. Antonopoulos, Ioannis Akoumianakis, Evangelia Daskalaki, Christos P. Kotanidis, Hidekazu Kondo, Kirsten Lee, Dilan Yesilyurt, Ileana Badi, Murray Polkinghorne, Naveed Akbar, Julie Lundgren, Surawee Chuaiphichai, Robin Choudhury, Stefan Neubauer, Keith M. Channon, Signe S. Torekov, Craig E. Wheelock and Charalambos Antoniades. Journal of American College of Cardiology, online May 24, 2021, doi: 10.1016/j.jacc.2021.03.314


Provided by Karolinska Institute

Non-invasive Electrolyte Levels’ Measuring Method Can Prevent Sudden Cardiac Death (Medicine)

Researchers from Kaunas University of Technology (KTU), Lithuania came up with the idea on how to measure fluctuating blood potassium levels non-invasively, through electrocardiogram.

Researchers from Kaunas University of Technology (KTU), Lithuania came up with the idea on how to measure fluctuating blood potassium levels non-invasively, through electrocardiogram. The researchers claim that their method may become a digital biomarker in the future for managing electrolyte levels. This would be a huge step towards preventing potentially life-threatening conditions among people who suffer from chronic kidney disease.

©KTU

Electrolytes and especially potassium, are paramount in the conduction of the heart’s cells. When electrolytes are too low or too high, the heart cannot contract normally, leading to dangerous arrhythmias and potentially sudden cardiac death.

“Electrolyte levels are kept within the healthy range by the kidneys. However, the patients with the last stage of chronic kidney disease, who have no renal function left, rely on hemodialysis to keep their electrolyte levels regulated. This means that they are prone to electrolyte imbalance in a 2-day-long hiatus between hemodialysis sessions”, explains Ana Rodrigues, researcher at KTU Biomedical Engineering Institute, one of the authors of the invention.

According to Rodrigues, with today’s aging society, it is estimated that the number of people requiring hemodialysis will markedly increase within 10 years. As people age, so do their kidneys. Research shows that up to 50 percent of seniors over the age of 75 can have kidney disease.

Abnormal electrolyte levels disturb the heart’s natural rhythm; such abnormalities can be reflected in the electrocardiogram. However, identifying electrolyte imbalance using an electrocardiogram is difficult due to confounding factors that mask these expected changes. The task becomes particularly complicated if electrolyte levels start to fluctuate beyond normal, but not reaching levels that require immediate medical attention.

The method proposed by the team of KTU researchers, tackles the problem through mathematical models that enable to quantify subtle changes that are not visible to the naked eye at the early stages of electrolyte imbalance. The method allows to spot potassium – the most arrhythmogenic electrolyte – induced changes in a certain part of the electrocardiogram.

“The initial results are promising. Our method may become a digital biomarker in the future for the management of electrolyte levels”, says Rodrigues.

Researchers in Lithuania came up with the idea which would allow measuring electrolyte balance noninvasively at home through an electrocardiogram. ©KTU

The method proposed by KTU researchers allows detecting abnormal potassium levels before the onset of life-threatening arrhythmias. Patients could then start hemodialysis sooner, decreasing the chance of hospitalization and even premature death.

Usually, in order to detect the changes in electrolyte balance, a blood sample would be drawn from a patient. However, blood samples are not routinely requested and cannot be drawn outside a clinical environment. Thus, researchers in Lithuania came up with the idea which would allow measuring electrolyte balance noninvasively at home through an electrocardiogram.

“Noninvasive monitoring of electrolyte levels is a very novel concept and is now in its infancy stages. Our paper is one of the first papers published on the topic and, to the best of our knowledge, the first to investigate potassium fluctuations in ambulatory settings between hemodialysis sessions”, says Rodrigues.

The research is the outcome of the close collaboration between KTU, Lithuanian University of Health Sciences (LSMU) and the University of Zaragoza, Spain.

At the moment, clinical studies involving 17 patients have been completed. The researchers are planning on continuing clinical trials with more patients in order to validate their findings. Their next goal is to create an algorithm that would include measuring different electrolyte levels, such as calcium.

Later on, the algorithm could be integrated into wearable wrist-worn device capable of acquiring electrocardiograms. Every once in a while, the patient would record a short electrocardiogram signal (roughly 2-min long) using their fingers, and the system would register the electrolyte levels. If electrolytes were at an alarming level, the clinic would be notified, and the patient would be instructed accordingly.

References: A. S. Rodrigues et al., “Noninvasive Monitoring of Potassium Fluctuations During the Long Interdialytic Interval,” in IEEE Access, vol. 8, pp. 188488-188502, 2020.
doi: 10.1109/ACCESS.2020.3031471 http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=9225155&isnumber=8948470

Provided by Kaunas University of Technology

Ultrasounds Show Impact Of COVID-19 on The Heart (Medicine)

Cardiac ultrasounds (also known as echocardiograms) are providing a view of the heart and the impact of the COVID-19 virus on patients. A new study by researchers at Icahn School of Medicine at Mount Sinai identifies different types of cardiac structural damage experienced by COVID-19 patients after cardiac injury that can be associated with deadly conditions including heart attack, pulmonary embolism, heart failure, and myocarditis. These abnormalities are associated with higher risk of death among hospitalized patients. The findings, published the October 26 issue of the Journal of the American College of Cardiology, offer new insights that may help doctors better understand the mechanism of cardiac injury, leading to quicker identification of patients at risk and guidance on future therapies.

Kaplan-Meier curves for all-cause mortality in patients with versus without myocardial injury (Panel A) and in patients with versus without myocardial injury according to the presence or absence of major echocardiographic abnormalities (Panel B). *Includes wall motion abnormalities, global left ventricular dysfunction, diastolic dysfunction, right ventricular dysfunction and presence of pericardial effusion. Event rates are censored at 20 days from hospital admission. ©Mount Sinai Health System.

“Early detection of structural abnormalities may dictate more appropriate treatments, including anticoagulation and other approaches for hospitalized and post-hospitalized patients,” says author Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital.

The international, retrospective study expands on Mount Sinai’s previous research showing that myocardial injury (heart damage) is prevalent among patients hospitalized with COVID-19 and is associated with higher risk of mortality. That study focused on the patients’ levels of troponin–proteins that are released when the heart muscle becomes damaged–and their outcomes (higher troponin levels mean greater heart damage).

This new work looked at the presence of cardiac troponin elevations in combination with the presence of echocardiographic abnormalities, and found that the combination was associated with worse prognosis and mortality than troponin elevations alone.

“This is one of the first studies to provide detailed echocardiographic and electrocardiographic data in hospitalized patients with COVID-19 and laboratory evidence of myocardial injury,” explains first and corresponding author Gennaro Giustino, MD, Cardiology Fellow at The Mount Sinai Hospital. “We found that among COVID-19 patients who underwent transthoracic echocardiography, these cardiac structural abnormalities were diverse and present in nearly two-thirds of patients.”

Researchers looked at transthoracic echocardiographic (TTE) and electrocardiographic (ECG) scans of 305 adult patients with confirmed positive COVID-19 admitted to four New York City hospitals within the Mount Sinai Health System (The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Queens, and Mount Sinai Beth Israel), Elmhurst Hospital in Queens, and two hospitals in Milan, Italy, between March and May 2020. Median age was 63 years and 67.2 percent were men. 190 patients (62.6 percent) had evidence of myocardial injury; 118 of them had heart damage at the time of hospitalization admission and 72 developed myocardial injury during hospitalization. Researchers found that patients with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers, and an increased prevalence of TTE abnormalities when compared to patients without heart injury.

Among patients with Covid-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Cardiac structural abnormalities included right ventricular dysfunction, left ventricular wall motion abnormalities, global left ventricular dysfunction, diastolic dysfunction and pericardial effusions. LV = Left Ventricular. ©Mount Sinai Health System.

Abnormalities were diverse, with some patients exhibiting multiple abnormalities. 26.3 percent had right ventricular dysfunction (which can be associated with pulmonary embolism and severe respiratory failure), 23.7 percent had regional left ventricular wall motion abnormalities (which can be associated with heart attacks), 18.4 percent had diffuse left ventricular dysfunction (which can be associated with heart failure/myocarditis), 13.2 percent had grade II or III diastolic dysfunction (a condition leading to stiffer cardiac chambers), and 7.2 percent had pericardial effusions (extra fluid around the heart that causes abnormal pumping of the heart).

The study went on to look at in-hospital mortality and troponin elevation. It shows that troponin elevation was 5.2 percent among patients who did not have heart injury, compared to 18.6 percent for patients with myocardial injury but without echocardiographic abnormalities, and 31.7 percent for patients with myocardial injury who also had echocardiographic abnormalities. Researchers adjusted for other major complications from COVID-19 including shock, acute respiratory distress syndrome, and renal failure.

“Our study shows that an echocardiogram performed with appropriate personal protection considerations is a useful and important tool in early identification of patients at greater risk for COVID-19-related cardiac injury, who may benefit from a more aggressive therapeutic approach earlier in their hospitalization,” says corresponding author Martin Goldman, MD, Arthur M. and Hilda A. Master Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai. “Additionally, because this is a new disease with lingering symptoms, we plan on following these patients closely using imaging to evaluate the evolution and hopefully resolution of these cardiac issues.”

“Echocardiograms have shown to be invaluable in providing critical information on patients who present with multiple cardiac complaints. Echocardiography is the only imaging modality that can be taken to the bedside and safely used for patients including those on ventilators,” says Lori Croft, MD, Associate Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai and Director of the Echocardiography Laboratory at The Mount Sinai Hospital. “Our findings will help guide care of Covid-19 patients during a critical time.”

Provided by Mount Sinai Health System