Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly ...different from heart failure with reduced EF in terms of etiology and natural history (
Graziani et al., 2018
). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (
Crea et al., 2017
). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (
Paulus and Tschope, 2013
). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (
Ohanyan et al., 2018
). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (
Graziani et al., 2018
;
Lam et al., 2018
). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.
Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use ...of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.
Background: Age-related remodelling has the potential to affect the microvascular response to hyperemic stimuli. However, its precise effects on the vasodilatory response to adenosine and contrast ...medium, as well as its influence on fractional flow reserve (FFR) and contrast fractional flow reserve (cFFR), have not been previously investigated. We investigate the impact of age on these indices. Methods: We extrapolated data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve (PROPHET-FFR) and The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting (MEMENTO) studies. Only lesions with a relevant vasodilatory response to adenosine and contrast medium were considered of interest. A total of 2080 patients, accounting for 2294 pressure recordings were available for analysis. The cohort was stratified into three age terciles. Age-dependent correlations with FFR, cFFR, distal pressure/aortic pressure (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated. The vasodilatory response was calculated in 1619 lesions (with both FFR and cFFR) as the difference between resting and hyperaemic pressure ratios and correlated with aging. The prevalence of FFR-cFFR discordance was assessed. Results: Age correlated positively to FFR (r = 0.062, p = 0.006), but not with cFFR (r = 0.024, p = 0.298), Pd/Pa (r = –0.015, p = 0.481) and iFR (r = –0.026, p = 0.648). The hyperemic response to adenosine (r = –0.102, p ≤ 0.0001) and to contrast medium (r = –0.076, p = 0.0023) showed a negative correlation with age. When adjusted for potential confounders, adenosine induced hyperaemia was negatively associated with age (p = 0.04 vs p = 0.08 for cFFR). Discordance decreased across age terciles (14.64% vs 12.72% vs 10.12%, p = 0.032). Conclusions: As compared to adenosine, contrast induced hyperaemia appeared to be less affected by age. cFFR may be considered a more stable and reproducible tool to assess epicardial stenosis in elderly patients. Clinical Trial Registration: PROPHET-FFR STUDY, Clinicaltrials.gov (NCT05056662).
Background
While the importance of invasive physiological assessment (IPA) to choose coronary lesions to be treated is ascertained, its role after PCI is less established. We evaluated feasibility ...and efficacy of Physiology-guided PCI in the everyday practice in a retrospective registry performed in a single high-volume and “physiology-believer” center.
Materials and methods
The PROPHET-FFR study (NCT05056662) patients undergoing an IPA in 2015–2020 were retrospectively enrolled in three groups: Control group comprising patients for whom PCI was deferred based on a IPA; Angiography-Guided PCI group comprising patients undergoing PCI based on an IPA but without a post-PCI IPA; Physiology-guided PCI group comprising patients undergoing PCI based on an IPA and an IPA after PCI, followed by a physiology-guided optimization, if indicated. Optimal result was defined by an FFR value ≥ 0.90.
Results
A total of 1,322 patients with 1,591 lesions were available for the analysis. 893 patients (67.5%) in Control Group, 249 patients (18.8%) in Angiography-guided PCI Group and 180 patients (13.6%) in Physiology-guided PCI group. In 89 patients a suboptimal functional result was achieved that was optimized in 22 cases leading to a “Final FFR” value of 0.90 ± 0.04 in Angiography-Guided PCI group. Procedural time, costs, and rate of complications were similar. At follow up the rate of MACEs for the Physiology-guided PCI group was similar to the Control Group (7.2% vs. 8.2%,
p
= 0.765) and significantly lower than the Angiography-guided PCI Group (14.9%,
p
< 0.001), mainly driven by a reduction in TVRs.
Conclusion
“Physiology-guided PCI” is a feasible strategy with a favorable impact on mid-term prognosis. Prospective studies using a standardized IPA are warrant to confirm these data.
New technologies have been recently introduced to improve the monitoring of patients with chronic syndromes such as heart failure. Devices can now be employed to gather large amounts of data and data ...processing through artificial intelligence techniques may improve heart failure management and reduce costs. The analysis of large datasets using an artificial intelligence technique is leading to a paradigm shift in the era of precision medicine. However, the assessment of clinical safety and the evaluation of the potential benefits is still a matter of debate. In this article, the authors aim to focus on the development of these new tools and to draw the attention to their transition in daily clinical practice.
At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical ...stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS.
To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum.
This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018.
Intracoronary OCT imaging of nonculprit coronary segments.
Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging.
Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% n = 24 of 30 vs 76.3% n = 29 of 38 vs 37.8% n = 14 of 37, respectively; P < .001; thin-cap fibroatheroma 40.0% n = 12 of 30 vs 34.2% n = 13 of 38 vs 8.1% n = 3 of 37, respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% n = 21 of 30 vs 40.5% n = 15 of 37 vs 44.7% n = 17 of 38, respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% n = 1 of 30 vs 29.7% n = 11 of 37 vs 28.9% n = 11 of 38, respectively; P = .01).
Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.
Abstract
Aims
Myocardial bridge (MB) is the most common inborn coronary artery variant in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of myocardium. MB has ...been documented from 1.5% to 16% of invasive angiographic series thus the true prevalence of MB is uncertain. The clinical relevance of MB is heterogeneous, being usually an asymptomatic bystander. However, a growing body of evidence suggests its association with myocardial ischaemia. In the present work, by setting up a database of patients affected by MB, we sought to assess their clinical characteristics and risk of major adverse cardiac events (MACE).
Methods and results
This is a prospective/retrospective study and observational study in which we included 17 681 patients referred to undergo invasive coronary angiography (ICA) for suspected coronary artery disease. During the screening phase, we found that 338 cases (26 non-recruitable) were reported to have MB (1.9%). In-hospital clinical-instrumental data was acquired after ICA. The data obtained in the follow-up (FUP) visit is also included in the study. In particular, we recorded MACE and Seattle Angina Questionnaire (SAQ). The most frequent location of MB was the LAD coronary artery (96.8%). Other locations were the circumflex artery (1.3%), the right coronary artery (1%), the posterior interventricular artery (0.6%), and the first diagonal artery (0.3%). Chronic coronary syndrome (CCS) was the most frequent clinical presentation (47.5%). A big proportion (34.6%) of our patients were found to have MB during the occurrence of an acute coronary syndrome (ACS). In acute setting, unstable angina was the most frequent clinical presentation (17.6%). 47 patients (15%) underwent coronary angiography with provocative test (intracoronary acetylcholine) in order to search vasomotor disorders: according to COVADIS criteria, 17 procedures (5.5%) resulted positive for vasospastic angina (VSA). Invasive functional assessment with FFR/iFR was accomplished to assess the haemodynamic significance both of MBs and atherosclerotic plaques proximal to the MB segment in 35 patients (11.2%): in nine procedures (2.9%), functional tests resulted positive. β-Blockers (BBs) are suggested as first-line drugs as they increase diastolic filling time, by decreasing heart rate. Calcium channel blockers (CCBs) are useful, in VSA setting, to reduce epicardial spasm. In our court, 40% of patients toke BBs and 20% of patients toke CCBs at admission. The primary endpoint of the study is the incidence of MACE, defined as the composite of cardiac death, myocardial infarction and cardiac hospitalization. Considering patients who have already undergone FUP (114; 36.5%), we recorded 19 MACE (16.7% of patients with FUP). The secondary endpoint is the rate of patients with SAQ Angina Summary Score < 70: the rate of patients with SAQ < 70 is 23.7% at 6 months, 23.8% at 12 months and 23.2% at 24 months.
Conclusions
MB has been typically considered benign and asymptomatic, but its clinical relevance is still matter of debate. A remarkable proportion of our patients were found to have a MB during the occurrence of ACS or CCS, highlighting that different mechanisms of ischaemia may coexist. Furthermore, invasive functional assessment shows a plausible correlation between MB and vasomotor disorders. Our study is still ongoing, and we hope to maximize the data in order to have a solid comprehension of MB and to propose the assessment that may indicate a tailored therapy.
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