Could the PARIS Risk Scores Be Useful for the Choice of Triple vs Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

Introduction. Current guidelines recommend dual antithrombotic therapy (DAT) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT) for those at very high thrombotic risk (TR) but low bleeding risk (BR). Methods. We analyze if the PARIS ischemic-hemorrhagic scale could be useful for the choice of antithrombotic strategy in patients with acute coronary syndromes (ACS) and AF treated with coronary stenting enrolled in the prospective, observational, nationwide MATADOR-PCI study. Results. Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients. According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate and 292 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized in the low, 260 (44.2%) in the intermediate and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n=130, 22%), followed by those at intermediate risk according to both scores (n=122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at intermediate to high TR but low BR, according to the PARIS score. Conclusion. Our data suggest that some variables associated with increased TR or BR are poorly considered in the daily practice while the use of PARIS scales could help in the implementation of guidelines' recommendations.

Cardiovascular Disease, Cancer and Multimorbidity Interactions: Clinical Implications

Background: With the aging population, the frequency of cardiovascular disease (CVD), cancer and other morbid conditions are increasing dramatically. In addition, one disease may affect the other leading to a vicious cycle. Summary: With aging, the function of organs and systems of the human body decline including the autoimmune system resulting in a diminished response to various pathogens and a chronic inflammatory process; these changes, in addition to other risk factors, contributes to the development of multiple morbid conditions including CVD and cancer. Multimorbidity in the elderly has become the rule rather than the exception today. Further, this association between CVD and cancer, at least partially, is explained by both diseases sharing common risk factors and from accelerated vascular aging due to cancer and its associated therapies. Multiple studies have shown that the incidence of cancer is much higher in patients with CVD compared to the general population. These associations among CVD, cancer and their connection to systems of the human body provide an opportunity for novel therapies. Development of new drugs should be addressed to focus on multiple systems and not just only to one disease. Further, collecting information from registries and processing large amounts of data using artificial intelligence may assist the clinician when treating an individual patient in the future. Key messages: As the aging population increases, CVD, cancer and multimorbidity will continue to constitute a major health problem in the years to come. The physician who is taking care of such a patient, in addition to knowledge, requires clinical wisdom, clinical experience and common sense in order to apply the continuous evolving knowledge to the individual patient.

Prognostic Importance of Pulmonary Artery Pulsatility Index and Right Ventricular Stroke Work Index in End-Stage Heart Failure Patients

Background: Right ventricular (RV) failure is an important cause of morbidity and mortality in patients with left ventricular (LV) end-stage heart failure (ESHF). Pulmonary artery pulsatility index (PAPi) and right ventricular stroke work index (RVSWI) are invasive parameters related to RV function. This study aimed to investigate the prognostic impact of PAPi and RVSWI in these patients. Methods and Results: In this study, 416 patients with ESHF were included. The adverse cardiac event (ACE) was defined as left ventricular assist device (LVAD) implantation, urgent heart transplantation, or cardiac mortality. There were 218 ACE cases and 198 non-ACE cases over a median follow-up of 503.50 days. Patients with ACE had lower PAPi and similar RVSWI compared to those without ACE (3.1±1.9 vs. 3.7±2.3, P=0.003 and 7.3±4.9 vs. 6.9±4.4, P=0.422, respectively). According to the results of multivariate analysis, while PAPi (from 2 to 5.65) was associated with ACE, RVSWI (from 3.62 to 9.75) was not associated with ACE (HR: 0.75, 95% CI (0.55-0.95), P=0.031; HR: 0.79, 95% CI: (0.58-1.09), P=0.081, , respectively). Survival analysis revealed that PAPi ≤2.56 was associated with a higher ACE risk compared to PAPi >2.56 (HR: 1.46, 95% CI: 1.11-1.92, P=0.006). PAPi ≤2.56 could predict ACE with 56.7% sensitivity and 51.3% specificity at one year. Furthermore, the association between RVSWI and ACE was nonlinear (J-curve pattern). Low and high values seem to be associated with higher ACE risk compared to intermediate values. Conclusion: The low PAPi was an independent risk for ACE and it had a linear association with it. However, RVSWI seems to be have a nonlinear association with ACE (J-curve pattern).

Unicuspid aortic valve: a rare congenital anomaly

Unicuspid aortic valve (UAV) is a rare congenital aortic valve anomaly. It has two subtypes and often is associated with aortic valve dysfunction and corresponding clinical presentations. Echocardiography is the first choice of diagnostic method for UAV. Three-dimensional echocardiography has played an increasingly important role in diagnosis, intraprocedural guidance, and post-procedural assessment in recent years. There remain challenges in distinguishing UAV from bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV). Misdiagnosis is most resulted from raphes or leaflet calcifications. Multi-modality imaging has obvious advantages over single-modality imaging and is crucial for UAV diagnosis. Accurate identification of aortic valve morphology is important to choose the best treatment. Aortic balloon valvoplasty, surgical valvotomy, commissurotomy, Ross procedure, surgical valve repair and surgical replacement are most common treatment modalities of UAV. In this review, we aim to discuss UAV including epidemiology, definition, classification, diagnostic importance and necessity, valvular function, clinical presentation, associated disorders, non-invasive diagnostic modalities and therapeutic approaches.

Reply: “Possible Takotsubo Syndrome”: A Refreshing Start Towards the path to Detect the True Prevalence of Takotsuobo Syndrome

Not applicable

Exhaled Methane is Associated with a Lower Heart Rate

Background: In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings we hypothesized that CH4 may be affecting resting heart rate based on the potential effect of CH4 on the vagus nerve. Objectives: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting heart rate (HR) in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association to breath CH4 over time. Methods: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post-hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 vs those that had a decrease in breath CH4 over 14 weeks. Lastly, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. Results: In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0±0.83 vs 76.0±0.44 beats/min; p=0.01). In the post-hoc analysis, a decrease in CH4 over time was associated with an increase in heart rate (median ∆ = 6.5 ± 8.32 beats/min, p=0.0006). Lastly, we demonstrated a biological gradient whereby a larger drop in CH4 is associated with a greater increase in heart rate (R= -0.31, p=0.03). Conclusion: Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate heart rate. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.

Drug-eluting versus bare metal stents in saphenous vein grafts compared to native coronary vessels. The NORSTENT study.

Background. Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The NORSTENT study is the first to randomize lesions to percutaneous coronary intervention (PCI) in native vessels and SVG. Aims. To compare rate of mortality, MI and TLR across stent and vessel types. Methods. In this substudy 6087 patients with a single lesion in native vessels and 164 in SVG, were followed for 5 years. Results. MI was more frequent in SVG (subdistributional hazard ratio (SHR) 4.95 (3.75 – 6.54, p<0.001), but not affected by stent type. In the first 500 days DES reduced TLR in native vessels (SHR 0.21 ( 0.15 – 0.30)p<0.001) and SVG (SHR 0.18 (0.04 – 0.80) p=0.02). Thereafter DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23 – 8.94) p=0.02). After 5 years the TLR rate was still significantly lower for DES in native vessels (3.2 % versus 7.8 %, p<0.001) but not in SVG (21.4 % vs 18. 4%). Conclusion: In SVG no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and myocardial infarction in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted.

Role of Signaling Pathways during Cardiomyocyte Differentiation of Mesenchymal Stem Cells

Multipotent stem cells, including mesenchymal stem cells (MSCs), represent a promising source to be used by regenerative medicine. They are capable of performing myogenic, chondrogenic, osteogenic and adipogenic differentiation. Also, MSCs are characterized by the expression of multiple surface antigens, but none of them appears to be particularly expressed on MSCs. Moreover, the prospect of monitoring and controlling MSC differentiation is a scientifically crucial regulatory and clinical requirement. Different transcription factors and signaling pathways are involved in cardiomyocyte differentiation. Due to the paucity of studies exclusively focused on cardiomyocyte differentiation of MSCs, present study aims at describing the roles of various signaling pathways (FGF, TGF, Wnt, Notch, etc.) in cardiomyocytes differentiation of MSCs. Understanding the signaling pathways that control the commitment and differentiation of cardiomyocyte cells not only will expand our basic understanding of molecular mechanisms of heart development, but also will enable us to develop therapeutic means of intervention in cardiovascular diseases.

“Possible Takotsubo Syndrome”: A Refreshing Start Towards the Path to Detect the True Prevalence of Takotsubo Syndrome

No Abstract

Victor J. Ferrans, MD, PhD (1937-2001)

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