Cohort Study Showed a Large Number of Patients Receiving Anticancer Therapy Demonstrate Myocardial Injury or Left Ventricular Dysfunction, With Only Few Showing Severe Cardiotoxicity

A recent study by Dr. Lopez-Sendon, published in European Heart Journal, showed that cardiotoxicity in the form of left ventricular dysfunction or myocardial injury affects a large portion of patients receiving high-risk anticancer therapy with only severe form strongly associated with all-cause mortality.

Cardiotoxicity has been known as one of the major side effects of anti-cancer therapy that may present with left ventricular dysfunction and heart failure. Given that the early recognition and treatment of these side effects have been associated with a higher recovery rate, a united diagnostic and management guideline seems necessary.

The CARDIOTOX (CARDIOvascular TOXicity induced by cancer-related therapies) registry has been established to determine the prevalence of cardiotoxicity markers as well as their association with guideline-based heart failure criteria and treatment in patients receiving chemotherapeutic agents. To achieve this purpose, a total of 865 patients receiving anticancer regimens associated with moderate to high cardiotoxicity were selected and followed for a median of 24 months. Clinical data, blood samples, and echocardiographic features were collected before the initiation of anticancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years afterward. Patients with past or current history of heart failure or reduced left ventricular ejection fraction (< 40%) and those with a history of previous cancer therapy including chemotherapy and radiation therapy were excluded from the study. Cardiotoxicity was defined as any new deterioration from the baseline of myocardial/ventricular function during follow-up periods. Cardiotoxicity was also sub-classified into four stages depending on the worst myocardial dysfunction/injury observed in the follow-up period. Myocardial dysfunction/injury stages include the following: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥ 50%; moderate, LVD with LVEF 40–49%; and severe, LVD with LVEF ≤ 40% or symptomatic heart failure.

The study indicated a high incidence (37.5%) of ventricular dysfunction among the patients, of whom only 3.1% were classified as having severe dysfunction and the majority have been classified as mild (31.6%). All-cause mortality was also observed to be higher among those with severe cardiotoxicity than other groups. According to the author, the relatively low prevalence of severe cardiotoxicity in the study population was due to the exclusion of patients with a previous history of cardiac dysfunction and the improvement in the follow-up of the cancer patients in the context of cardio-oncology service. Severe cardiotoxicity has also been associated with a 10-fold increase in total mortality compared to a less severe form of cardiotoxicity. A classification of cardiotoxicity using current heart failure guidelines is also proposed by the authors for future studies. This study acknowledged the critical role of comprehensive monitoring and follow-up for the development of cardiovascular symptoms and left ventricular dysfunction in patients receiving chemotherapeutic agents with potential cardiotoxicity.

Limitations that are worthy of mentioning include the inclusion of patients with some degree of abnormality in biomarkers and echocardiographic findings at baseline. Secondly, the prevalence of myocardial damage may be underestimated due to a number of missing visits or incomplete data collection during the follow-up period. Future research is warranted to approve the relationship of different stages of cardiotoxicity with clinical outcomes.

Population-Based Cohort Study Shows Blood Pressure Trajectories Over The Life Course Progress More Rapidly in Women Compared to Men

A new study by Dr. Hongwei, published in JAMA Cardiology, demonstrated that blood pressure (BP) trajectories over the life course progress more rapidly in women compared to men, a process that begins as early as the third decade of life. This concept is inconsistent with the previously accepted notion that important vascular disease processes in women occur by 10 to 20 years delay compared to men. These sex-based differences in physiology may establish the cornerstone for future cardiovascular disorders that often present differently in women compared with men.

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Study Shows Hepatitis C Status Not Associated With Adverse Events in Adult Heart Transplant Patients by 1 Year

A recent study by Dr. Kilic, published in the American Heart Association Journal, showed similar adverse outcomes in the 1-year survival, rejection rates, and complications of patients who received a heart transplant using hepatitis C-positive (HCV+) donors whereas those using hepatitis C-negative donors.

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Randomized Trial Shows Prasugrel Associated with Better Endothelial Function and Stronger Platelet Inhibition as Compared to Clopidogrel or Ticagrelor in Patients with ACS Who Undergo Stenting

In a recent randomized, three-arm, parallel, blinded study by Dr. Schnorbus, published in European Heart Journal, prasugrel was associated with improved endothelial function, more potent platelet inhibition, and decreased plasma interleukin (IL)-6 levels in patients undergoing stent placement for acute coronary syndrome (ACS) compared to ticagrelor and clopidogrel. These effects were observed in patients who received prasugrel 2 hours before stenting.

Coronary artery stenting has been associated with impaired coronary and peripheral endothelial function as well as an inflammatory response leading to the release of mediators and subsequent platelet aggregation. These phenomena are associated with in-stent restenosis as well as adverse prognostic outcomes after percutaneous coronary intervention (PCI). Platelet inhibitors, such as P2Y12 receptor inhibitors, are administered prior and after coronary interventions to address these adverse effects. However, previous studies have suggested that differences exist among P2Y12 inhibitors in terms of their efficacy.

In a prospective, single-center study, a total of 90 patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI) undergoing coronary stenting were randomized to receive a single dose of clopidogrel (600mg), prasugrel (60mg), or ticagrelor (180mg) followed by chronic therapy with the same drug. Patients with elevated c reactive protein (CRP), infective or inflammatory disorders, personal history of prior coronary interventions, impaired hepatic/renal function, those with heart failure, and those with ST elevation myocardial infarction (STEMI) were excluded from the study. The primary endpoint of the study was the change in flow-mediated dilation (FMD) of the conduit artery over a period of 1 day, 1 week, and 1 month after PCI. Secondary endpoints were the effect of study medications on macrovascular and microvascular function, platelet aggregation, and inflammatory stress.

The study showed that antiplatelet therapy immediately before stenting was associated with improved FMD without a significant difference among study medications. On the first follow-up after PCI and later follow-up visits, prasugrel was associated with a stronger platelet reactivity inhibition and improved endothelial function. These effects were limited to those who received prasugrel before catheterization. Prasugrel platelet inhibitory effect was more obvious in NSETMI patients than in those with unstable angina. Prasugrel therapy also led to a more pronounced decrease in IL-6 levels. According to the author, “when administered pre-PCI, prasugrel, but not the other agents, limits stent-induced endothelial dysfunction and inflammation in ACS.” This study is limited by its small size and future studies are needed to further confirm these conclusions.

 

The Sarcomeric Human Cardiomyopathy Registry: Race Associated with Disease Expression and Clinical Outcomes Among Patients with Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy and race: differences in disease expression, inequitable care provision, and disparate clinical outcomes

Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic disorder of the myocardium, and the number one culprit of sudden cardiac death in athletes, particularly African Americans.

“Is race associated with differential disease expression, inequitable care provision, or disparate clinical outcomes among patients with hypertrophic cardiomyopathy?”

In order to answer the above question, Lauren A. Eberly, et al. studied 2,467 patients with hypertrophic cardiomyopathy. In a retrospective cohort study, black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018 compared in terms of baseline characteristics; genetic architecture; adverse outcomes such as cardiac arrest, cardiac transplantation or left ventricular assist device implantation, cardioverter-defibrillator implantation, all-cause mortality, atrial fibrillation, stroke,  prevalence and likelihood of developing heart failure; and receiving septal reduction therapies.

According to the results of this study (8.3 percent black; 91.7 percent white), published in the JAMA CARDIOLOGY (December 2019), compared with white patients, black patients with HCM were younger (mean age, 36.5 versus 41.9 years), were less likely to have sarcomere mutations (26.1 versus 40.5 percent), had a higher prevalence of New York Heart Association (NYHA) class III or IV heart failure at presentation (22.6 versus 15.8 percent) and were more prone to developing heart failure (hazard ratio, 1.45). Lower rates of genetic testing (26.1 versus 40.5 percent) have been observed in black patients. Although there were no racial differences in implantation of implantable cardioverter-defibrillators, the invasive septal reduction was less common among African Americans (14.6 versus 23 percent). Nevertheless, Black patients had fewer incidents of atrial fibrillation (35 [17.1 percent] versus 608 [26.9 percent].

The results of this study were in accordance with the previous studies that mentioned a higher prevalence of complicated hypertrophic cardiomyopathy in African Americans in contrast to the lower prevalence of HCM in this community.  Eberly, et al. believe that racial differences in disease expression and adverse clinical outcomes are not only because of different characteristics of the disease in African Americans but also inequities in clinical care provision might be responsible for these observed differences.

Intensive LDL Lowering With a Goal of < 70mg/dl Is Superior to Moderate Lowering for Secondary Prevention of Ischemic Stroke Patients 8.5% of patients assigned to the group with intensive LDL lowering suffered from recurrent MACE including recurrent ischemic stroke compared to 10.9% of patients in the modest control approach

A randomized parallel-group trial comparing intensive LDL-C lowering to modest lowering for prevention of major adverse cardiovascular events (MACE) in patients with recent ischemic stroke in the setting of atherosclerosis has shown that an aggressive LDL-C reduction strategy with a goal of < 70mg/dl is superior to modest reduction approach which targets a range of 90-110 mg/dl.

Results of the Treat Stroke to Target Trial (TST trial) which enrolled 2860 patients (32% females) with a median follow-up of 3.5 years were presented by Dr. Amarenco (Department of Neurology and Stroke Center, Bichat Hospital, France) at AHA 2019 and simultaneously published in The New England Journal of Medicine.

Patients with established atherosclerotic cardiovascular disease (ASCVD) and ischemic stroke within the past 3 months or transient ischemic stroke (TIA) within the past 15 days (modified Rankin score of 0-3) were randomized in 1:1 fashion to statin therapy with either a goal LDL-C of < 70 mg/dl (n =1430) or 90-110 mg/dl (n = 1430).

The primary efficacy endpoint of the trial was composite of MACE (nonfatal cerebral infarction or stroke of undetermined origin, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary-artery revascularization, TIA treated with urgent carotid revascularization, or CV death). The primary outcome occurred in 8.5% of patients assigned to the group with intensive LDL lowering compared to 10.9% of patients in the modest control approach (adjusted hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.04). Mean LDL-C levels at baseline were 135 mg/dl for both groups and at 3.5 years for the intensive vs. modest treatment groups were 65 vs. 96 mg/dl (p < 0.05). Secondary outcomes were occurrence of MI, need for urgent revascularization, all-cause mortality, intracranial hemorrhage, and newly diagnosed diabetes mellitus. Rates of intracranial hemorrhage (1.3% vs. 0.9% [p > 0.05]) and new-onset diabetes mellitus (7.2% vs. 5.7% [p > 0.05]) were numerically higher with more aggressive control, but not statistically significant.

The present study highlights the clinical benefit obtained by a tighter control of plasma LDL levels for secondary prevention of stroke. Previously, the SPARCL trial showed that in patients who have had a stroke within the prior one to six months without coronary artery disease, treatment with 80 mg atorvastatin led to a lower incidence of recurrent MACE including fatal and nonfatal strokes. In the Heart Protection Study (HPS), simvastatin 40mg did not show benefit in secondary stroke protection, but in HPS, patients were enrolled after a mean of 4.3 years of having a cerebrovascular accident, whereas the greatest risk for recurrent strokes resides within the first year of suffering from a cerebrovascular accident.  Though findings from the current TST trial are in line with the SPARCL trial in terms of reduction of recurrent MACE, the SPARCL trial saw an increase in the incidence of hemorrhagic strokes in the treatment arm, while the present TST clinical trial revealed no rise in hemorrhagic stroke rates in patients despite achieving more aggressive reductions in their serum LDL-C levels.

The authors ask the readers to interpret the results of the TST trial while considering the fact that the study was stopped prematurely due to insufficient funding at 3.5 years and did not reach the goal of 385 events, instead, 277 primary events were recorded for the analysis. In addition, secondary endpoints could not be tested due to the failure of hierarchical clustering of endpoints.

GALILEO-4D: Rivaroxaban-Aspirin Based Anti-Thrombotic Therapy Post-TAVR Protects From Valve Leaflet Motion Abnormalities Rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis

An expanded analysis of 231 patients from the GALILEO trial comparing rivaroxaban-aspirin based anti-thrombotic therapy with clopidogrel-aspirin based dual anti-platelet therapy post transcatheter aortic valve replacement (TAVR), has shown that the rivaroxaban based regimen protects from valve leaflet motion abnormalities. The rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis. Continue reading

Treatment with Statins, RAAS Inhibitors and Platelet Inhibitors After CABG is Essential, While the Use of Beta-blockers is Questionable: Swedish Study Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry

In a recent study published in the European Heart Journal, Erik Björklund et al. found that the secondary prevention medications, such as statins and renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors used after coronary artery bypass grafting (CABG) are essential while the use of B-blockers had no association with survival and is questionable.

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Positive Correlation Found Between Combined Life-time Exposure of Decreased LDL-C and Low Systolic BP in Lowering the Risk of Cardiovascular Disease Mendelian randomization analyses involving approximately half a million participants reveals the association of lifelong genetic exposure to lower levels of low-density lipoprotein cholesterol and lower systolic blood pressure with lower cardiovascular risk

A recent study by Brian A. Ference et al. based on a UK Biobank study, published in JAMA, has shown that life-time exposure to decreased low-density lipoprotein cholesterol (LDL-C) levels and low systolic blood pressure (SBP) leads to a decreased lifetime risk of cardiovascular disease. Nonetheless, these findings do not constitute the quantified benefit of treating these risk factors in decreasing the life-time cardiovascular disease risk.

This randomized study included the data from 438, 952 individuals who were the participants of the UK Biobank study with the mean age of 65.2 years (range: 40.4 – 80.0 years) and 54.1% female participants. Participants were divided into a total of 4 groups, and 4 x 4 factorial reasoning was carried out. First participants were divided into 2 groups based on having a genetic LDL-C score being equal to or lower than, or higher than the median value. Second, they were further subdivided into 2 groups based on having their genetic systolic BP score being equal to, or lower than, or higher than the median value. The reference group further included 3 groups with each individual group having a higher LDL-C genetic score than the median, higher SBP scores than the median, and combined LDL-C and SBP genetic scores higher than the median, respectively. Differences in the plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to evaluate the correlations with the lifetime cardiovascular disease risk. The primary outcome included major coronary events which were characterized as a composite of coronary death, coronary revascularization, or nonfatal myocardial infarction. The key secondary outcomes were major cardiovascular events defined as the occurrence of a major coronary event or ischemic stroke.

When compared with the reference group, participants having LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels with an Odds ratio of 0.73 for major coronary events (95%CI: 0.70 – 0.75; P < 0.001). Participants with SBP genetic scores higher than the median had 2.9 mmHg lower SBP with an Odds ratio of 0.82 for major coronary events (95%CI: 0.79 – 0.85; P < 0.001). Finally, the participants in the group with both genetic scores higher than the median had 13.9 mg/dL lower LDL-C, 3.1 mmHg lower SBP, with an Odds ratio of 0.61 for major coronary events (95%CI: 0.59 – 0.64; P < 0.001). In a 4×4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67 mg/dL lower LDL-C and 10 mmHg lower SBP was associated with an Odds ratio of 0.22 for major coronary events (95%CI: 0.17 – 0.26; P < 0.001), and 0.32 for cardiovascular death (95%CI: 0.25 – 0.40; P < 0.001). These findings concluded the positive correlation of lifelong genetic exposure to lower LDL-C levels and lower SBP with the overall lower cardiovascular disease risk without any regard to the magnitude of benefit achieved after treating these risk factors.

There are several limitations to this study, including the lack of evaluation of risks and benefits of medications associated with lowering the LDL-C and SBP. Second, there is a lack of evidence proving that outcomes associated with naturally occurring lower LDL-C or SBP levels are the same as the outcomes associated with extrinsic drug treatment or other interventions to achieve similar plasma LDL-C or SBP levels. Hence, these study findings fail to quantify the amount of benefit gained from various treatments to lower LDL-C, SBP, or both.

REVELATION Trial: Paclitaxel-Coated Balloon Angioplasty is Non-Inferior To The Routinely Conducted Drug-Eluting Stenting in STEMI Patients A 9 months follow-up Single-Centered Randomized Clinical Trial

According to a recent study based on the REVELATION Trial, conducted by Nicola S. Vos et al. and published in JACC, Paclitaxel-coated balloon angioplasty was documented to be non-inferior to the routine drug-eluting stenting (DES) in ST-segment elevation myocardial infarction (STEMI) patients.

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No significant association between myocardial viability & long-term survival benefit of CABG in patients with ischemic cardiomyopathy Results of a 10-year follow-up STICH trial & subsequent myocardial viability sub-study

According to a new study published in The New England Journal of Medicine (NEJM) based on a 10-year follow-up STICH trial, no association was found between myocardial viability as a long-term survival benefit of CABG in patients with ischemic cardiomyopathy.

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PolyIran Trial: Polypill Prevents Cardiovascular Events PolyIran Trial: Fixed-Dose Combination Therapy With Aspirin, a Statin and Two Anti-hypertensives Reduced Cardiovascular Events As Compared to Non-Pharmacological Intervention

A four-component polypill, including aspirin, atorvastatin, hydrochlorothiazide, and enalapril or valsartan, effectively reduced major cardiovascular events in a real-life setting study. The results of the PolyIran trial by Roshandel G. et al. was published in Lancet.

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Population Based Cohort Study: With or Without AFib, CHA₂DS₂-VASc Score is a Sensitive Predictor and Stratifies the Risk of MACCE 22,000 Patient Study Showed Increased Risk of Ischemic Stroke and New-Onset Atrial Fibrillation in Patients Without Atrial Fibrillation

Giulia Renda et al. recently published in the European Journal of Preventive Cardiology that the CHA2DS2-VASc score is a sensitive measure of predicting new-onset atrial fibrillation (AF) and adverse outcomes in patients with and without atrial fibrillation in the middle-aged patient population. Continue reading

11,000 Patient Study Demonstrates That Higher 24 hour and Nighttime Blood Pressure Readings Associated With Increased Risk of Cardiac Events

In an original investigation done by Dr.Wen-Yi Yang and his team, the results of which got published in JAMA, concluded that raised 24-hour and nighttime blood pressure (BP) readings are linked to increased risk of death and composite cardiovascular outcomes significantly. They considered it to be an optimal way of measuring risk but noted the difference was small for the improvement in the model.

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Vascular Risk Factors Tied to Unhealthy Brains, Study from UK Biobank Suggests

Vascular risk factors such as smoking, hypertension, and diabetes were associated with poor brain health. The study by Cox et al., recently published in the European Heart Journal, revealed.

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IMPROVE-IT Trial: Intensive Lipid-Lowering Cuts CVD Risk in the Elderly

Among patients hospitalized for an acute coronary syndrome (ACS), adding ezetimibe to simvastatin further reduced the risk of cardiovascular events, and the benefit was ten times greater in the elderly than younger individuals. A secondary analysis of the IMPROVE-IT trial, published in JAMA Cardiology, revealed.

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Nationwide Study Shows New-onset Left Bundle Branch Block After Transcatheter Aortic Valve Replacement Occurred in 15% of Intermediate Risk Patients and Is Associated with Worse 2 Year Outcomes

According to a new nationwide study,  new onset left bundle branch block (LBBB) post transcatheter aortic valve replacement (TAVR), a recently established therapy for intermediate risk surgical candidates with symptomatic, severe aortic stenosis, is associated with adverse long term clinical outcomes in patients without baseline conduction disturbances or pacemaker.  Based on the findings published in the European Heart Journal, these outcomes include cardiovascular mortality, re-hospitalization, new pacemaker implantation, and worsened left ventricular systolic function in intermediate risk patients.

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1.3 Million Patient Study Shows That Even With New Lower Definition for Hypertension, Elevated Systolic and Diastolic Blood Pressure Both Independently Increase Risk of Cardiovascular Events

In a recent original cohort study done by Alexander C. Flint and his team published in the New England Journal of Medicine, it was concluded that systolic hypertension, as well as diastolic hypertension, independently affects the risk of cardiovascular adverse events irrespective of the cutoffs used for hypertension(≥140/90 mm Hg or ≥130/80 mm Hg).

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Meta-analysis Shows Vitamin D Supplementation Does Not Improve Cardiovascular Outcomes

In the largest updated meta-analysis study conducted to understand the inverse association between low serum vitamin D supplementation and increased cardiovascular disease (CVD) risks, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality) or all-cause mortality.  The findings published in the Journal of the American Medical Association Cardiology suggest vitamin D supplementation may not confer cardiovascular protection and may not be indicated for this purpose. Continue reading

Latest Cross-Sectional Study Links Dietary Pattern Specific Protein Biomarkers to Development of Cardiovascular Disease

According to a nationwide cross-sectional study, protein biomarkers along with specific dietary patterns are linked to the development of cardiovascular disease (CVD). These findings, published in the Journal of the American Heart Association, suggest associations between dietary patterns and protein biomarkers have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion and metabolism. Over the years, the role of diet in the prevention of CVD has been scientifically proven; unhealthy dietary components are important risk factors for the total global burden of this comorbidity. Continue reading