Dynamic modulation of coronary arterio-venous communications

A 62 year-old man with multiple coronary risk factors – including uncontrolled hypertension, smoking habit, abdominal obesity and family history of ischemic heart disease – was admitted to our Emergency Department for a prolonged episode of chest pain occurring at rest. He had no relevant past medical history except recently diagnosed chronic obstructive pulmonary disease; however, in the last year he suffered from sporadic episodes of effort angina (Canadian Class II–III) with spontaneous regression after few minutes of rest. During the last week he experienced worsening angina, with daily episodes of chest pain, mainly occurring during mild exertion but with some episodes occurring even at rest in the last two days. On admission the patient was symptomatic for angina. Physical examination was unremarkable, except for rhonchi and wheezing sounds in the chest, the blood pressure was 200/95 mmHg and the ECG revealed sinus tachycardia with ST segment elevation and QS waves in V1–V4 leads. Pharmacological treatment was immediately started with loading doses of Aspirin and Clopidogrel, iv. morphine, i.v. nitroglycerin and i.v. beta-blockers, with partial pain resolution. Cath lab team was promptly alerted for urgent coronary angiography. In the meantime, a trans-thoracic echocardiogram was performed, showing a hypertrophic and mildly dilated left ventricle with regional wall motion abnormalities in the left anterior descending (LAD) coronary artery territory: apical and mid septal akinesia, anterior wall hypokinesia. The estimated left ventricular ejection fraction was 35–40%. No other relevant findings. Fifteen minutes after the admission the patient was still mildly symptomatic for angina and ST segment elevation was still present on the ECG, although reduced, thus the patient was transferred directly to the cath lab to undergo coronary angiography. The selective right coronary angiography revealed significant stenosis of the posterolateral branch of the right coronary artery (RCA) and, more importantly, the presence of collaterals to the LAD and three artero-venous fistulae, which allowed the RCA to communicate with the pulmonary artery, the coronary sinus and a posterolateral branch of the cardiac venous system (Fig. 1A ). Prior to the selective angiography of the left coronary artery, the patient's chest pain resolved together with the concomitant resolution of the ST segment elevation. The left coronary angiography (Fig. 2C ) was performed and showed the presence of significant proximal LAD stenosis, likely representing the culprit lesion, which appeared spontaneously reperfused. Angiography also revealed sub-occlusion of the first diagonal and significant stenosis of the first obtuse marginal (OM) branch. Due to these findings, a new right coronary angiography was performed, which documented the disappearance of both arterial and venous communications (Fig. 1 B). Because of the spontaneous reperfusion of the culprit lesion, together with the total regression of symptoms and ST segment elevation, urgent revascularization was not deemed necessary. Furthermore, considering the presence of multivessel disease, a joint clinical case meeting with cardiac surgeons and invasive cardiologists was arranged and a staged PCI was felt to be the best treatment option and thus was scheduled the following day. A successful revascularization procedure was performed with the implantation of two everolimus eluting stents (EES), 2.75×23 mm on LAD and 2.75×32 mm on OM, and a POBA of the first diagonal branch with a 2.5×25 mm balloon. The patient was discharged with the indication to complete the percutaneous revascularization later. The pre-discharge echocardiogram confirmed global left ventricular dysfunction (LVEF 35–40%) with the above described regional wall motion abnormalities. One month later the revascularization was completed with an elective PCI of the posterolateral branch of the RCA with the implantation of another EES 2.75×16 mm and the angiography confirmed the complete disappearance of collateral circulation and arterio-venous fistulae (Fig. 2 D,E)

The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: Study protocol for a randomized controlled trial

Background: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G-CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. Methods/Design: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) ≤45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1year. Discussion: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. Trial registration: ClinicalTrials.gov: NCT02502747(29 June 2015); EudraCT: 2015-002189-21 (10 July 2015)

Come orientarsi tra contropulsatore, Impella e ossigenazione a membrana extracorporea

The use of percutaneous mechanical circulatory support systems in the setting of both high-risk percutaneous coronary intervention (PCI) and cardiogenic shock is an emerging, controversial issue in contemporary clinical cardiology. The most common devices are the intra-aortic balloon pump (IABP), the Impella and the extracorporeal membrane oxygenator (ECMO). Technical progress, equipment improvement and growing cath-lab team expertise are allowing to offer critical patients different levels of assistance according to the selected device. Indeed, they are extremely different and the selection of the proper device for each clinical scenario might be tricky. In high-risk PCI, mechanical hemodynamic support serves the purpose of preventing hemodynamic collapse during the procedure. According to baseline risk stratification, IABP or Impella are usually considered whereas ECMO is seldom considered as a third option for highly selected patients. Cardiogenic shock and cardiac arrest are still associated with high mortality rates. In these conditions mechanical support may be promising. The lack of benefit observed with the systematic use of the IABP (combined with the increased mortality associated with higher number of inotropic drugs) is actually prompting to increasingly consider Impella and ECMO use in critically ill patients. The development of multidisciplinary local protocols is considered pivotal to improve management and outcome of those patients requiring percutaneous circulatory support devices

Hypersensitivity myocarditis or Kounis syndrome?

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Stent malapposition, strut coverage and atherothrombotic prolapse after percutaneous coronary interventions in ST-segment elevation myocardial infarction

Stent implantation in ST-segment elevation myocardial infarction (STEMI) patients can be challenging and sometimes associated with immediate and long-term suboptimal results. Stent malapposition and strut uncoverage, predictors of stent thrombosis, are frequently detected in STEMI patients at medium/long-term follow-up. Nevertheless, data at a short follow-up are missing. We aimed to assess the extent of stent malapposition and struts coverage in the subacute phase of STEMI after stent implantation in primary or rescue percutaneous coronary intervention (PCI)

Transcatheter closure of atrial septal defect using intracardiac echocardiography: a two-center, retrospective study

Aims: We present the experience and long-term results of intracardiac echocardiography (ICE)-guided closure of ostium secundum atrial septal defects (ASDs) in two Italian centers and investigate its systematic applicability as the gold standard in routine clinical practice. Methods: We retrospectively evaluated all consecutive patients who underwent an ASD percutaneous closure procedure from March 2008 to February 2020. All patients underwent a preprocedural transesophageal echocardiography (TEE) evaluation. The closures were carried out under fluoroscopic and ICE guidance. A follow-up visit was performed at 1, 3 and 12 months, followed by telephone evaluations approximately every 2 years. Results: Sixty-six patients (29% male individuals), mean age 43 ± 16 years, were treated. In 15 cases, the TEE defect diameter was less than 10 mm, and in 8 of these patients, the ICE intraprocedural sizing increased the maximum diameter by more than 5 mm. Sizing balloon of the defect was performed in 51 cases; 2 patients received an ASD 38 mm device. Eight patients had multiple defects; in three of these, it was necessary to apply two devices. Four patients showed nonsignificant residual shunt; no complications related to the use of ICE were observed. One patient presented the migration of the ASD device into the abdominal aorta, percutaneously retrieved with a snare. No major complications were recorded during the entire follow-up period. Conclusion: This study confirms that ICE monitoring during ASD percutaneous closure is well tolerated and effective; it might be achievable as a routine gold standard by operators willing to use ICE systematically in all transcatheter closure interventions of interatrial communications

Adenosine-Free Indexes vs. Fractional Flow Reserve for Functional Assessment of Coronary Stenoses: Systematic Review and Meta-Analysis

Background: Adenosine-free indexes (AFIs), including resting Pd/Pa, instantaneous wave-free ratio (iFR) and contrast-FFR (cFFR), have been proposed to circumvent the use of vasodilators, in order to simplify the functional evaluation of coronary stenoses. Aims of this study were to analyze the correlation between AFIs and Fractional Flow Reserve (FFR) and to compare their diagnostic accuracy when FFR is used as reference. Methods: We conducted a systematic review and meta-analysis of observational studies in which AFIs were compared to FFR. We produced paired forest plots to show the variation of the sensitivity and specificity estimates. We used a hierarchical summary ROC model (HSROC) to summarize the sensitivity and specificity of AFIs in detecting the concordance with FFR assessment. Results: Eighteen studies were included in this meta-analysis. Overall, 4424, 4822 and 2021 coronary lesions in 4410, 4472 and 1898 patients, respectively, were evaluated by Pd/Pa, iFR and cFFR, respectively. The overall Pearson's correlations were 0.81 (95%CI 0.78-0.83), 0.80 (95%CI 0.78-0.81) and 0.92 (95%CI 0.90-0.94) for Pd/Pa, iFR and cFFR, respectively. cFFR showed a significantly higher correlation with FFR compared to Pd/Pa and iFR (p < 0.0001). The area under the HSROC estimating the discriminating accuracy of cFFR was 0.95 (95%CI 0.94-0.96) and it was significantly higher compared to Pd/Pa (0.86, 95%CI 0.80-0.93) and iFR (0.89, 95%CI 0.84-0.94) (p < 0.0001). Conclusions: AFIs show a good correlation with the gold standard FFR. Among AFIs, cFFR shows the highest correlation with FFR and the best diagnostic accuracy

Fractional flow reserve in acute coronary syndromes and in stable ischemic heart disease: clinical implications

Background: Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD) is universally accepted, while in Acute Coronary Syndromes (ACS) is less established. Aims of this retrospective study were: to compare in patients undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the clinical relevance of the modality of utilization and timing of FFR assessment and to assess the different outcomes associated with an FFR> or 640.80. Methods: Major cardiac adverse events were assessed at a follow up of 16.4 \ub1 10.5 months in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was used for lesions of ambiguous significance in the absence of a clear culprit vessel (first intention, FI) and for incidental lesions in the presence of a clear culprit vessel (second intention, SI). The decision to perform FFR and the identification of the stenosis needing functional assessment were left to the operator's discretion. Revascularization was performed when FFR was 640.80. Results: SIHD and ACS patients were not significantly different for principal clinical characteristics. ACS patients had significantly more events than SIHD, due to an excess of death and myocardial infarction. This was confirmed when FFR was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was used as SI, event rates were similar between ACS and SIHD patients, regardless of FFR value. Conclusions: Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. This different outcome is confined to those patients in whom FFR is utilized for lesions of ambiguous significance in the absence of a clear culprit vessel