Key Points:

• There is uncertainty determining who is likely to develop dysglycemia and type 2 diabetes mellitus (T2DM) due to weight gain and adiposity: 80% of those with obesity do not develop T2DM, and 50% of persons with T2DM do not have obesity.
• Targeting weight loss to certain individuals could personalize the prevention of T2DM, helping determine who is most likely to benefit from weight loss therapy to prevent T2DM.
• A total of 445,765 participants in the UK Biobank were analyzed, of whom 28,563 developed T2DM, in order to infer if more T2DM cases are inherited or acquired, to determine if there is optimal timing of T2DM prevention, and to ascertain if certain groups are more likely to benefit from T2DM prevention.
• Given substantial variation in the effect of BMI on A1c depending on multiple variables, individuals may have a “personal weight threshold” for developing T2DM that could be individually targeted.

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A recent study by Dr. Jason G. Andrade, published in New England Journal of Medicine, found that the use of catheter cryoablation as first-line therapy for patients with newly diagnosed, symptomatic, paroxysmal atrial fibrillation is associated with lower recurrence of arrhythmia and a better quality of life when compared to an antiarrhythmic treatment approach. Continue reading →

A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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A recent trial by Dr. Jordana B Cohen, published in The LANCET, indicated that consistent with international society recommendations, patients admitted to the hospital with COVID-19 can safely continue treatment with renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)) unless there is a distinct medical contraindication to ongoing therapy.

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A recent study by Dr. Milton Packer, published in Circulation, demonstrated that empagliflozin use has been associated with a reduction in the total number of inpatient and outpatient visits in patients with heart failure and a reduced ejection fraction. These benefits were observed within  12-28 days of treatment initiation and were persisted over the duration of the trial. Continue reading →

Results of the DAPA trial, published in Circulation: Arrhythmia and Electrophysiology, demonstrated that the use of early prophylactic implantable cardioverter defibrillator (ICD) in high-risk post-primary percutaneous coronary intervention (PCI) patients was associated with lower all-cause and cardiac mortality rates. However, the results of this trial should be interpreted with caution, since the trial was stopped prematurely.

The optimal timing of ICD implantation in STEMI patients treated with primary angioplasty is not identified yet. Previous clinical trials have failed to show the benefit of early ICD implantation (4-60 days) in post-MI patients with a low left ventricular ejection fraction (≤35-40%). The risk of sudden cardiac death (SCD) is high within the post STEMI period.  However, ICD implantation after 40 days may not be indicated due to left ventricular remodeling and a potential increase in LVEF post-primary PCI. The Defibrillator After Primary Angioplasty (DAPA) trial evaluated all-cause and cardiac mortality of patients undergoing early prophylactic ICD implantation after PCI for STEMI. Following a recommendation from the data safety board, the trial was terminated early after just 38% of the planned sample size was enrolled due to slow enrollment.

This multicenter, randomized, controlled trial included patients with STEMI who had undergone primary PCI and met at least one of the following criteria: LVEF<30% within 4 days after admission, primary ventricular fibrillation (VF) within 24 hours (during PCI excluded), signs of heart failure on admission (Killip class ≥ 2), and/or thrombolysis in myocardial infarction (TIMI) flow post PCI < 3. The participants were randomized in a 1:1 ratio to receive either ICD implantation or conventional therapy within 30 to 60 days of the STEMI event. The primary endpoint was all-cause mortality at 3 and 9-years. The secondary endpoints of the study included the incidence of sudden cardiac death (SCD) and hospital admission for sustained ventricular tachyarrhythmias or appropriate ICD therapy.

A total of 266 patients with primary PCI for STEMI were included in the study with 131 patients allocated to the ICD arm and 135 patients assigned to the conventional therapy arm. After 3-years of follow-up, the primary outcome of interest was significantly lower among patients who received ICD implantation (5%) compared to the conventional therapy group (13%) (Hazard ratio (HR):0.37; [95% CI: 0.15-0.95]; p=0.04). This result remained similar at a median of 9-years follow-up (HR: 0.58; [95% CI: 0.37-0.91]; p=0.02). In terms of cardiac mortality, ICD implantation was associated with fewer deaths (11%) compared to the control group (22%) (HR: 0.52; [95% CI: 0.28-0.99]; p=0.04). Although not statistically significant, the incidence of SCD was also lower in the ICD group (3.1%) compared to the control group (5.9%) (HR 0.45; [95% CI 0.14–1.50]; p=0.19).

The results of this study should be interpreted with consideration of the following limitations. First, the premature termination of the study makes it underpowered for analysis. Second, the study used more than one inclusion criteria, so results should be interpreted with consideration of the patient characteristics. The high treatment crossovers (10.2%) within the first 3 years of the study and the lack of information on treatment crossovers between 3 and 9 years are additional limitations of the trial.  Furthermore, while pharmacotherapy of the participants was similar at baseline, there is a lack of data regarding the follow-up medical therapy which may have impacted the mortality rates.

In conclusion, this prematurely terminated trial suggests that early prophylactic ICD implantation may be associated with a better survival rate in patients at high risk of death after primary PCI for STEMI. The results of this trial should be confirmed in future studies.

A recent study by Dr. Banerjee, published in Circulation: Cardiovascular Interventions, demonstrated the efficacy and safety of low-density lipoprotein (LDL) lowering therapy via a single LDL apheresis treatment plus ongoing statin therapy in nonfamilial hyperlipidemia acute coronary syndrome patients treated with the percutaneous coronary intervention (PCI).
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A recent study by Dr. Salaun, published in Circulation: Cardiovascular Interventions, demonstrated that aortic valve replacement in patients with the low gradient (LG, defined as mean gradient <40 mmHg) severe aortic stenosis (AS) and preserved ejection fraction (EF) has resulted in better outcomes versus in those with the high gradient (HG, defined as a mean transvalvular gradient (MG) ≥ 40 mmHg) AS. Also, the study revealed that patients with classical low flow, low gradient (CLF-LG, defined as MG <40 mmHg and LVEF <50%) AS were at higher risk of death, rehospitalization, or stroke at 2 years.

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A recent study by Dr. Duthoit, MD, published in Circulation: Cardiovascular Interventions, showed that compared to dual antiplatelet therapy, nonvitamin k antagonist monotherapy using a reduced dose of rivaroxaban (10 and 15 mg) in patients undergone left atrial appendage closure was associated with lower thrombin generation. This data supported that reduced rivaroxaban doses could be a substitute for the antithrombotic medications currently used after this procedure. Continue reading →

A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading →

A recent study by Dr. O’Donoghue, published in Circulation, shows that early aspirin discontinuation with continued P2Y12 inhibitor monotherapy, after the percutaneous coronary intervention (PCI),  was associated with a significant reduction in major bleeding compared to dual antiplatelet therapy. This study did not show a significant increase in major adverse cardiovascular events (MACE) after aspirin discontinuation in the participants.
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A recent study by Dr. Julinda Mehilli, M.D., published in Circulation journal, has shown that in patients undergoing elective percutaneous coronary intervention (PCI), pretreatment strategy with the intensified prasugrel loading does not differ from standard clopidogrel loading dose in terms of Safety and Efficacy. According to the trial, both strategies can be safely applied among patients undergoing elective PCI.
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Dr. Mark J. Eisenberg and his colleagues presented the interim results of the E3 trial to the American College of Cardiology 2020 Meeting. The study was also published in the CJC open journal. According to the E3 trial, the most efficacious way for smoking cessation is nicotine e-cigarettes (ECs) with counseling followed by non-nicotine ECs with individual counseling and individual counseling alone.

Given the clear health benefits of smoking cessation and the increasing desire of smokers for adopting e-cigarettes as a way of quitting smoking, it sounds reasonable to evaluate the efficacy of these agents in smoking abstinence. However, the increasing number of e-cigarettes-associated lung injuries has questioned the safety of these products. The E3 trial aimed at evaluating the efficacy and safety of e-cigarettes for smoking cessation in the general population.

The E3 trial, a multi-center randomized controlled trial, recruited participants motivated for smoking cessation. Individuals with severe diseases and a prognosis of less than a year, a current or recent history of cancer, a current or recent history of drug abuse or a recent history of cardiovascular or cerebrovascular disease, a history of psychiatric disorders and those using e-cigarettes or other medications for smoking cessation were excluded from the study. This resulted in 376 participants who were randomized into three management arms: nicotine ECs, non-nicotine ECs, or no e-cigarettes.  All of them received individual counseling. Treatment allocation for ECs groups was double-blind. The treatment period was done for 12 weeks and individuals were followed for 52 weeks. Follow-up sessions were performed via phone interview (4 sessions) as well as in-person clinic visits (4 sessions). The primary endpoint was the comparison of nicotine-ECs with individual counseling in terms of biochemically-validated point-prevalence smoking abstinence at 12 weeks. The secondary endpoints included the evaluation of ECs efficacy in terms of continuous smoking abstinence and reduction in daily cigarette use as well as ECs safety profile.

In an interview with Dr. C. Michael Gibson, Dr. Mark J. Eisenberg, one of the investigators in the study, discussed the interim results of the study. Point-prevalence abstinence was higher for those who were treated with nicotine-ECs and counseling compared to those who only received counseling (22% versus 9%). In terms of safety, one of the individuals in nicotine-ECs developed COPD exacerbation, and 5 individuals in the non-nicotine ECs group also developed a variety of side effects including epistaxis and chest pain. The E3 trial is going to follow the patients for up to 1 year and the results of this study will be updated. This study will provide health care professionals, and smokers with important information regarding the efficacy and safety of e-cigarettes for smoking cessation.

Click here to listen to the discussion between Dr. C. Michael Gibson and Dr. Eisenberg.

Click here to view the study slides.

In an original investigation done by Dr. Alexander C. Fanaroff et al and recently published in JAMA Cardiology, it was found that there was discordance in medication persistence as measured by patient-reported and the pharmacy fill data. The patient self-reports overestimated and pharmacy fill data underestimated medication persistence. Those who had non-persistence by both measures had the highest rate of major adverse cardiovascular events (MACE). The authors also noted the need for giving preference to interventions that will promote medication-taking behavior. Continue reading →

A recent study by Dr. Knott, published in Circulation, have shown the prognostic value of measuring myocardial blood flow (MBF) using artificial intelligence quantification of cardiovascular magnetic resonance (CMR) perfusion mapping in cardiovascular outcomes. According to this study, both MBF and myocardial perfusion reserve (MPR) were associated with death and major adverse cardiovascular events (MACE) independently of other clinical risk markers. Using this technique, quantitative analysis of myocardial perfusion for clinical use is now available. Continue reading →

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.

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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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.

In an original study conducted by Dr. Aleksandr Voskoboinik et al. recently published in The New England Journal of Medicine, it was found that alcohol consumption is a modifiable risk factor for Atrial Fibrillation (AFib) and abstinence from alcohol in people with AFib causes a reduction in burden and recurrence rates of AFib. Continue reading →

In an original article written by Leroy C. Joseph et al, it was found the molecular mechanisms of cardiac metabolism to arrhythmia and NAPDH Oxidase2(NOX2) deletion or pharmacological inhibition can prevent arrhythmia caused due to the ingestion of a high saturated fat diet. The results of the study were published in Circulation: Arrhythmia and Electrophysiology. Continue reading →