Left ventricular diastolic function in atrial fibrillation: Methodological implications and clinical considerations.

The assessment of LVDD is routinely included in echocardiographic evaluation because it correlates with cardiac disease progression and its prognostic value. Classic parameters used for assessing LV diastolic function correlate well with invasive measurements which remains the gold standard. Nevertheless, no one echocardiographic parameter alone can completely evaluate LVDD. LV diastolic function evaluation in atrial fibrillation is still challenging, since the E/A ratio, one of the most used parameters in echocardiographic evaluation, cannot be feasible. This is not a good reason to give up measurement. In this review, we analyze the different methods for estimating LV diastolic function in atrial fibrillation, including measurement not dependent on atrial systole and some novel methods that are promising, but not ever available during clinical practice highlighting that this assessment is mandatory for a complete clinical evaluation of the patients.

Pathophysiology and Treatment of the No-Reflow Phenomenon in ST-Segment Elevation Myocardial Infarction: Focus on Low-Dose Fibrinolysis during Primary Percutaneous Intervention.

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the 'no-reflow' phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

Gender-related differences in changes of estimated bleeding risk in patients on dual antiplatelet therapy: the RE-SCORE multicenter prospective registry.

The risk of bleeding as predicted by the PRECISE-DAPT score can vary over time after percutaneous coronary intervention (PCI). We sought to compare the predictive ability of the PRECISE-DAPT score calculated at baseline and reassessed during follow-up in male and female patients undergoing PCI. The RE-SCORE was a multicenter, prospective registry including patients undergoing PCI treated with dual antiplatelet therapy (DAPT) for 1 year. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The PRECISE-DAPT score was determined for each patient at the time of PCI and at 1, 4 and 8-month follow-up visits or before the occurrence of an endpoint event. A total of 480 patients undergoing PCI were included. At baseline, median PRECISE-DAPT score was similar in males (23.2 [IQR 20.1-24.2]) and females (23.4 [IQR 20.2-25.3]; p = .22). During follow-up, an increase in the PRECISE-DAPT occurred significantly more often in females (44%) than in males (23%; p < .001). The discrimination of the PRECISE-DAPT score calculated at baseline was marginal in both males (c-index = 0.59, 95% CI: 0.51-0.65) and females (c-index = 0.55, 95% CI: 0.49-0.60). The discriminative ability of the score reassessed at follow-up was excellent in females (c-index = 0.84; 95% CI: 0.77-0.91) but remained modest in males (c-index = 0.61; 95% CI: 0.55-0.70). The bleeding predictive ability of the PRECISE-DAPT score can vary over time, more commonly in females than males. The discrimination of the score calculated during follow-up appeared improved in females but remained modest in males.Clinical Trial Registration - ClinicalTrials.gov Identifier: NCT03526614.

Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5 years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.

Pathophysiology of Takotsubo Syndrome.

Originally described by Japanese authors in the 1990s, Takotsubo syndrome (TTS) generally presents as an acute myocardial infarction characterized by severe left ventricular dysfunction. TTS, however, differs from an acute coronary syndrome because patients have generally a normal coronary angiogram and left ventricular dysfunction, which extends beyond the territory subtended by a single coronary artery and recovers within days or weeks. The prognosis was initially thought to be benign, but subsequent studies have demonstrated that both short-term mortality and long-term mortality are higher than previously recognized. Indeed, mortality reported during the acute phase in hospitalized patients is ≈4% to 5%, a figure comparable to that of ST-segment-elevation myocardial infarction in the era of primary percutaneous coronary interventions. Despite extensive research, the cause and pathogenesis of TTS remain incompletely understood. The aim of the present review is to discuss the pathophysiology of TTS with particular emphasis on the role of the central and autonomic nervous systems. Different emotional or psychological stressors have been identified to precede the onset of TTS. The anatomic structures that mediate the stress response are found in both the central and autonomic nervous systems. Acute stressors induce brain activation, increasing bioavailability of cortisol and catecholamine. Both circulating epinephrine and norepinephrine released from adrenal medullary chromaffin cells and norepinephrine released locally from sympathetic nerve terminals are significantly increased in the acute phase of TTS. This catecholamine surge leads, through multiple mechanisms, that is, direct catecholamine toxicity, adrenoceptor-mediated damage, epicardial and microvascular coronary vasoconstriction and/or spasm, and increased cardiac workload, to myocardial damage, which has a functional counterpart of transient apical left ventricular ballooning. The relative preponderance among postmenopausal women suggests that estrogen deprivation may play a facilitating role, probably mediated by endothelial dysfunction. Despite the substantial improvement in our understanding of the pathophysiology of TTS, a number of knowledge gaps remain.

A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

BACKGROUND: Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. METHODS: We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. RESULTS: All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. CONCLUSIONS: The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.

Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights.

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three-dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image-guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography.

Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in stable patients with coronary artery disease treated with dual antiplatelet therapy : The ROMAN (RanOlazine vs. aMlodipine on platelet reactivity in stable patients with CAD treated with dual ANtiplatelet therapy) study.

Amlodipine, commonly used for relief of ischemic symptoms in coronary artery disease (CAD), may affect clopidogrel-induced antiplatelet effects. It remains unknown if ranolazine, an antianginal drug that constitutes a pharmacologic alternative to calcium channel blockade, interferes with clopidogrel-induced antiplatelet effects. The aim of the ROMAN study was to compare the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in clopidogrel treated patients with CAD. A prospective, randomized, cross-over, open-label study conducted in a total of 210 CAD patients on aspirin (100 mg/q.d.) and clopidogrel (75 mg/q.d.) 1 month following percutaneous coronary intervention. Patients were randomly assigned to amlodipine (10 mg p.d., n = 105) or ranolazine (750 mg b.i.d., n = 105) for 15 days, and after a 1-week wash-out period, crossed-over treatment for 15 days. P2Y12 reaction units (PRU) were assessed at baseline and after each treatment sequence. High on-treatment platelet reactivity (HPR) was defined as a PRU > 208. Amlodipine was associated with higher PRU than ranolazine (182 ± 75 vs. 167 ± 64, p = 0.028). As compared with baseline, PRU increased significantly after treatment with amlodipine (p = 0.018), but was not different after ranolazine therapy (p = 0.871). Changes in platelet reactivity following amlodipine therapy appeared to depend on baseline HPR status, as PRU levels significantly increased only among HPR subjects. In stable CAD patients treated with dual antiplatelet therapy after PCI, concomitant treatment with amlodipine, but not ranolazine, interferes with clopidogrel-induced antiplatelet effects.

Clinical effects of routine postdilatation of drug-eluting stents.

OBJECTIVES: To assess the clinical effects of postdilatation of drug-eluting stents (DES). BACKGROUND: Subotpimal stent expansion occurs after DES deployment. Postidlatation may improve DES expansion, but it is unclear whether postdilatation may also improve clinical outcomes. METHODS: Since July 2009, we adopted a strategy of routine postdilatation with noncompliant balloons of all DES, while previously postdilatation was performed only for suboptimal results. The first 279 consecutive patients (age 62 ± 9 years, 231 men) who underwent routine postilatation were compared with 262 patients (age 61 ± 9 years, 220 men) who received DES in the previous 6 months (standard treatment). RESULTS: The two groups were similar for age, sex, clinical presentation, and main risk factors, including incidence of diabetes. Routine postdilatation resulted in an improved minimal lumen diameter at the end of the procedure (2.60 ± 0.34 vs. 2.51 ± 0.37 mm, P = 0.003). At 12-month follow-up incidence of MACE (including periprocedural myocardial infarction) was 19.5% in the standard treatment group and 12.5% in routine postdilatation group (P = 0.04), with a significant difference in target vessel revascularization (10.7% vs. 5.4%, P = 0.03), while incidence of myocardial infarction was not significantly different between the two groups (10.7% vs. 9.3%, P = 0.70). Stent thrombosis (definite or probable) occurred in 3 patients in standard treatment group, while no case of stent thrombosis occurred among patients treated with routine postdilatation (1.1% vs. 0%, P = 0.11). CONCLUSIONS: Our results suggest that a strategy of routine postdilatation with non compliant balloons may improve clinical outcomes of DES.

Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual antiplatelet therapy.

BACKGROUND: Levels of platelet reactivity in patients on dual antiplatelet therapy (DAPT) can be influenced by concomitant treatment with statins. We verified if the pharmacodynamic effects of CYP3A4-metabolized statins (atorvastatin) and non-CYP3A4-metabolized statins (pitavastatin) differ in patients with coronary artery disease (CAD) treated with DAPT. METHODS AND RESULTS: A total of 155 CAD patients receiving DAPT (clopidogrel 75mg plus aspirin 100mg) entered the PORTO trial. Patients were randomly assigned to atorvastatin (20mg day) or pitavastatin (4mg day) for 30 days, and then switched to the other drug for 30 days. Platelet reactivity was expressed as VerifyNow P2Y12 platelet response units (PRU) before and after each 30-day treatment period. High platelet reactivity was defined as PRU >208. As compared with pretreatment (192±49), PRU was significantly higher after 30-day atorvastatin (210±56; P=0.003), but was unchanged after 30-day pitavastatin (199±47 PRU, NS). In the 48 patients with PRU >208 at baseline (232±44), PRU increased significantly after 30-day atorvastatin (258±41, P=0.004), but not after 30-day pitavastatin (237±43, NS). In the 107 patients with PRU <208 at baseline (174±52), PRU did not change significantly with respect to baseline either after 30-day atorvastatin (188±61, NS) or after 30-day pitavastatin (181±59, NS). CONCLUSIONS: Pitavastatin, a non-CYP3A4-metabolized statin, does not affect clopidogrel's response as compared with atorvastatin in patients who are borderline or poor responders to DAPT.

Feasibility of anticoagulation on demand after percutaneous coronary intervention in high-bleeding risk patients with paroxysmal atrial fibrillation: the INTERMITTENT registry.

Aims: This study evaluated the feasibility of the intermittent use of direct oral anticoagulants (DOACs) guided by continuous rhythm monitoring via a clinically validated wearable smart device in high-bleeding risk (HBR) patients with symptomatic paroxysmal atrial fibrillation (AF) otherwise subjected to chronic anticoagulation after percutaneous coronary intervention (PCI). Methods and results: The INTERMITTENT registry was a 3-year prospective observational study at eight Italian centres. Inclusion criteria were elective or urgent PCI, Academic Research Consortium HBR criteria, history of symptomatic 12-lead ECG detected paroxysmal AF episodes, indication to DOACs, and use of a wearable smart device (Apple Watch™). Thirty days after PCI, patients free of AF episodes discontinued DOAC. However, if an AF episode lasting >6 min or a total AF burden > 6 h over 24 h was detected, DOAC was initiated for 30 consecutive days, and withdrawn afterwards if no further AF episodes occurred. At the discretion of the referring physician, intermittent anticoagulation was offered to 89 patients, whereas continuous treatment with DOACs was prescribed to 151 patients. During a follow-up of 298 ± 87 days, the average duration of oral anticoagulation was significantly shorter in the intermittent anticoagulation group (176 ± 43 days, P = 0.0001), representing a 40% reduction in anticoagulation time compared to the continuous group. Ischaemic and bleeding endpoints were not significantly different between the two groups. Propensity score-matching resulted in a total of 69 matched patients with intermittent vs. continuous anticoagulation, respectively. During a follow-up of 291 ± 63 days, there was a significant 46% reduction in anticoagulation time in the intermittent compared to the continuous group (P = 0.0001). Conclusion: In HBR patients with a history of paroxysmal AF episodes who underwent PCI, intermittent anticoagulation guided by continuous rhythm monitoring with a wearable device was feasible and decreased significantly the duration of anticoagulation.

Therapeutic strategies aiming at the reduction of the antiplatelet intensity should not overlook the ischemic risk in patients with coronary syndromes.

De-escalation of dual antiplatelet therapy (DAPT) is gaining traction as a strategy to reduce bleeding risks while ensuring ischemic outcomes. Undiscriminating de-escalation, notably in patients with high ischemic risk, might expose them to major adverse cardiac events. Platelet function and genetic tests are emerging tools to guide de-escalation, but both present specific drawbacks. Recent meta-analyses have aimed to consolidate the findings of individual trials to provide clearer insights. Yet, limitations remain for patients with concomitant high bleeding and ischemic risks. These high-risk patients are frequently underrepresented in clinical trials, and, therefore, currently available guidelines lack evidence-based recommendations for this subset. While DAPT de-escalation strategies hold promise, the choice of approach, whether clinically or assay-guided, remains complex and should be individualized.

Biomechanical factors and atherosclerosis localization: insights and clinical applications.

Although the entire vascular bed is constantly exposed to the same risk factors, atherosclerosis manifests a distinct intra-individual pattern in localization and progression within the arterial vascular bed. Despite shared risk factors, the development of atherosclerotic plaques is influenced by physical principles, anatomic variations, metabolic functions, and genetic pathways. Biomechanical factors, particularly wall shear stress (WSS), play a crucial role in atherosclerosis and both low and high WSS are associated with plaque progression and heightened vulnerability. Low and oscillatory WSS contribute to plaque growth and arterial remodeling, while high WSS promotes vulnerable changes in obstructive coronary plaques. Axial plaque stress and plaque structural stress are proposed as biomechanical indicators of plaque vulnerability, representing hemodynamic stress on stenotic lesions and localized stress within growing plaques, respectively. Advancements in imaging and computational fluid dynamics techniques enable a comprehensive analysis of morphological and hemodynamic properties of atherosclerotic lesions and their role in plaque localization, evolution, and vulnerability. Understanding the impact of mechanical forces on blood vessels holds the potential for developing shear-regulated drugs, improving diagnostics, and informing clinical decision-making in coronary atherosclerosis management. Additionally, Computation Fluid Dynamic (CFD) finds clinical applications in comprehending stent-vessel dynamics, complexities of coronary bifurcations, and guiding assessments of coronary lesion severity. This review underscores the clinical significance of an integrated approach, concentrating on systemic, hemodynamic, and biomechanical factors in atherosclerosis and plaque vulnerability among patients with coronary artery disease.

Cardiovascular Effects of Cosmic Radiation and Microgravity.

Recent spaceflights involving nonprofessional people have opened the doors to the suborbital space tourism business. However, they have also drawn public attention to the safety and hazards associated with space travel. Unfortunately, space travel involves a myriad of health risks for people, ranging from DNA damage caused by radiation exposure to the hemodynamic changes that occur when living in microgravity. In fact, the primary pathogenetic role is attributed to cosmic radiation, since deep space lacks the protective benefit of Earth's magnetic shielding. The second risk factor for space-induced pathologies is microgravity, which may affect organ function and cause a different distribution of fluid inside the human body. Both cosmic radiation and microgravity may lead to the alteration of cellular homeostasis and molecular changes in cell function. These, in turn, might have a direct impact on heart function and structure. The aim of this review is to draw attention to the fact that spaceflights constitute a novel frontier in biomedical research. We summarize the most important clinical and experimental evidence regarding the cardiovascular effects of cosmic radiation and microgravity. Finally, we highlight that unraveling the mechanisms underlying how space radiation and microgravity affect the cardiovascular system is crucial for identifying potential countermeasures and developing effective therapeutic strategies.

Red Blood Cell Transfusion Strategies in Cardiovascular Interventions.

Acute coronary syndrome, cardiac surgery, and cardiac structural interventions are among the most common situations leading to allogeneic red blood cell consumption due to the prevalence of bleeding and anemia. The wide variability in the use of transfusions derives from the current lack of data, and the absence of strong evidence and clear guideline recommendations. The current approach is to avoid unnecessary blood transfusions and limit their use to life-saving conditions; this conservative strategy derives from often controversial and inconclusive results of observational and randomized studies where liberal and restricted red blood transfusion strategies seemed to have similar outcomes. The pivotal question for future research lies in elucidating whether blood transfusions function as an active participant or merely a catalyst in amplifying adverse events. The present review aims to summarize the current literature data and critically analyze the available evidence for red blood transfusions in cardiac interventions.

Management of high and intermediate-high risk pulmonary embolism: A position paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology.

Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress. Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role.