Management of vulnerable patient phenotypes and acute coronary syndrome mechanisms.

Atherosclerosis is a chronic vascular disease. Its prevalence increases with aging. However, atherosclerosis may also affect young subjects without significant exposure to the classical risk factors. Recent evidence indicates clonal hematopoiesis of indeterminate potential (CHIP) as a novel cardiovascular risk factor that should be suspected in young patients. CHIP represents a link between impaired bone marrow and atherosclerosis. Atherosclerosis may present with an acute symptomatic manifestation or subclinical events that favor plaque growth. The outcome of a plaque relies on a balance of innate and environmental factors. These factors can influence the processes that initiate and propagate acute plaque destabilization leading to intraluminal thrombus formation or subclinical vessel healing. Thirty years ago, the first autopsy study revealed that coronary plaques can undergo rupture even in subjects without a known cardiovascular history. Nowadays, cardiac magnetic resonance studies demonstrate that this phenomenon is not rare. Myocardial infarction is mainly due to plaque rupture and plaque erosion that have different pathophysiological mechanisms. Plaque erosion carries a better prognosis as compared to plaque rupture. Thus, a tailored conservative treatment has been proposed and some studies demonstrated it to be safe. On the contrary, plaque rupture is typically associated with inflammation and anti-inflammatory treatments have been proposed in response to persistently elevate biomarkers of systemic inflammation. In conclusion, atherosclerosis may present in different forms or phenotypes. Vulnerable patient phenotypes, identified by using intravascular imaging techniques, biomarkers, or even genetic analyses, are characterized by distinctive pathophysiological mechanisms. These different phenotypes merit tailored management.

Novel Medical Treatments and Devices for the Management of Heart Failure with Reduced Ejection Fraction.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of "heart failure with reduced ejection fraction" (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

Recurrent events after acute ST-segment elevation myocardial infarction: predictors and features of plaque progression and stent failure.

OBJECTIVES: Patients with acute ST-segment elevation myocardial infarction (STEMI) are at high risk for recurrent coronary events (RCE). Non-culprit plaque progression and stent failure are the main causes of RCEs. We sought to identify the incidence and predictors of RCEs. METHODS: Eight hundred thirty patients with STEMI were enrolled and followed up for 5 years. All patients underwent blood test analysis at hospital admission, at 1-month and at 12-month follow-up times. Patients were divided into RCE group and control group. RCE group was further categorized into non-culprit plaque progression and stent failure subgroups. RESULTS: Among 830 patients with STEMI, 63 patients had a RCE (7.6%). At hospital admission, HDL was numerically lower in RCE group, while LDL at both 1-month and 12-month follow-up times were significantly higher in RCE group. Both HDL at hospital admission and LDL at 12-month follow-up were independently associated with RCEs (OR 0.90, 95% CI 0.81-0.99 and OR 1.041, 95% CI 1.01-1.07, respectively). RCEs were due to non-culprit plaque progression in 47.6% of cases, while in 36.5% due to stent failure. The mean time frame between pPCI and RCE was significantly greater for non-culprit plaque progression subgroup as compared to stent failure subgroup (27 ±â€…18 months and 16 ±â€…14 months, P  = 0.032). CONCLUSION: RCEs still affect patients after pPCI. Low levels of HDL at admission and high levels of LDL at 12 months after pPCI significantly predicted RCEs. A RCE results in non-culprit plaque progression presents much later than an event due to stent failure.

Cardiac Contractility Modulation Therapy in Patients with Amyloid Cardiomyopathy and Heart Failure, Case Report, Review of the Biophysics of CCM Function, and AMY-CCM Registry Presentation.

Cardiac amyloidosis may result in an aggressive form of heart failure (HF). Cardiac contractility modulation (CCM) has been shown to be a concrete therapeutic option in patients with symptomatic HF, but there is no evidence of its application in patients with cardiac amyloidosis. We present the case of TTR amyloidosis, where CCM therapy proved to be effective. The patient had a history of multiple HF hospitalizations due to an established diagnosis of wild type TTR-Amyloidosis with significant cardiac involvement. Since he was highly symptomatic, except during continuous dobutamine and diuretic infusion, it was opted to pursue CCM therapy device implantation. At follow up, a significant improvement in clinical status was reported with an increase of EF, functional status (6 min walk test improved from zero meters at baseline, to 270 m at 1 month and to 460 m at 12 months), and a reduction in pulmonary pressures. One year after device implantation, no other HF hospital admission was needed. CCM therapy may be effective in this difficult clinical setting. The AMY-CCM Registry, which has just begun, will evaluate the efficacy of CCM in patients with HF and diagnosed TTR amyloidosis to bring new evidence on its potential impact as a therapeutic option.

Long-term Results of Perfusion-Balloon Valvuloplasty, Without Rapid Pacing, in High-Risk Elderly Patients With Severe Aortic Stenosis: A New Space Oddity.

BACKGROUND: Percutaneous balloon aortic valvuloplasty (BAV) is actually recommended as a bridge to surgery or transcatheter aortic valve replacement in patients with severe aortic stenosis (AS) in particular clinical settings. In this pilot study, for the first time, we report our experience utilizing a nonocclusive balloon for BAV, which does not require rapid ventricular pacing (RVP), in high-risk symptomatic elderly patients with severe AS. METHODS AND RESULTS: From 2018 to 2020, a total of 30 high-risk elderly patients with heart failure due to severe AS were treated with BAV and were all prospectively included in the study. We used a perfusion-balloon valvuloplasty without RVP (True Flow; BD/Bard). Hemodynamic parameters were invasively evaluated during catheterization, before and immediately after BAV. All patients were regularly followed to detect the rate of mortality. The patients were 87.56 ± 4.10 years old and 23% were males. In the catheterization laboratory, the peak left ventricular to aortic pressure gradient significantly decreased from 55 mm Hg (interquartile range [IQR], 48.75-66.25) to 26 mm Hg (IQR, 15.7-30) immediately after balloon inflation (P<.001). The median value of percentage decrease of transaortic gradient was 56% (IQR, 50-74). At a median of 12 months (IQR, 5-27) follow-up, 12 patients (40%) died. The median time between BAV and mortality was 10.5 months (IQR, 1.75-15.5). At multivariable analysis, the only predictor of mortality was the New York Heart Association class at admission (odds ratio, 3.29; 95% confidence interval, 2.4-298.4; P<.01). CONCLUSION: This single-center pilot study represents the first evidence that perfusion-balloon valvuloplasty without RVP is a safe, valid, and durable option in high-risk, symptomatic, elderly patients with severe AS.

Coronary Plaque Rupture in Stable Coronary Artery Disease and Non-ST Segment Elevation Myocardial Infarction: An Optical Coherence Tomography Study.

BACKGROUND: Plaque rupture (PR) is the main cause of coronary thrombosis in non-ST segment elevation myocardial infarction (NSTEMI), but can be found in stable coronary artery disease (CAD). Our study compared the morphology and local inflammatory activity of ruptured plaques between stable CAD and NSTEMI patients using frequency-domain optical coherence tomography (FD-OCT). METHODS: We retrospectively evaluated 70 plaques with PR at the FD-OCT (25 in stable CAD patients and 45 in NSTEMI patients). Main clinical, angiographic, and morphological features were compared. RESULTS: Besides an overall equivalence in clinical and angiographic features (except for more smokers among NSTEMI patients), some important FD-OCT differences in plaque morphology emerged: PR in NSTEMI was characterized by more macrophage infiltrates (78% in NSTEMI patients vs 20% in stable CAD patients; P<.001) and intraluminal thrombosis (84% in NSTEMI patients vs 48% in stable CAD patients; P<.01). Quantitative analysis showed a higher density of macrophages in NSTEMI than in stable CAD patients: median max normalized standard deviation (NSD) was 0.0934 (IQR, 0.0796-0.1022) vs 0.0689 (IQR, 0.0598-0.0787); P<.01 and mean NSD was 0.062 (IQR, 0.060-0.065) vs 0.053 (IQR, 0.051-0.060); P<.001. Other morphological features did not differ between stable CAD and NSTEMI patients. Main FD-OCT quantitative parameters like minimal lumen area and plaque length were also equivalent between the 2 groups. CONCLUSIONS: Differences in morphological features of PR between stable CAD and NSTEMI patients suggest that local inflammation contributes to the unstable fate of the atherosclerotic plaque.

Appropriate use criteria for coronary angiography: a single centre experience.

BACKGROUND: Increasing attention is being given to the rational use of invasive procedures. In this study, we aimed to evaluate, among patients referred for coronary angiography, the appropriateness of cardiac catheterization according to the Appropriate Use Criteria (AUC) for diagnostic catheterization and to examine the relationship between the appropriateness and the presence of obstructive coronary artery disease (CAD) and revascularization. METHODS: From November 2017 to December 2018, 1188 consecutive patients referred to undergo a diagnostic catheterization were included. They were categorized as having appropriate, uncertain or inappropriate indication, using a database (Melograno System). We restricted our analysis to 9 appropriate indications including acute coronary syndromes, suspected CAD, valvular heart disease, arrhythmias and cardiomyopathy. We restricted the analysis to the subgroup of patients with suspected or known CAD and, among them, we evaluate the rate of CAD and the need for revascularization. RESULTS: The indications were appropriate in 1017 patients (85.6%), of uncertain appropriateness in 134 (11.3%), and inappropriate in 37 (3.1%). Restricting the analysis to the CAD subgroup, the indications were appropriate in 848 patients (83.3%), of uncertain appropriateness in 133 (13.1%) and inappropriate in 37 (3.6%). The proportion of patients with critical CAD were 75.9%, 44.3% and 29.7% in the appropriate, uncertain and inappropriate categories respectively (p < 0.001). The revascularization rate was 63.1%, 32.2% and 21.6% in the appropriate, uncertain and inappropriate categories respectively (p < 0.001). CONCLUSIONS: Application of AUC is feasible in a community setting. Melograno system is useful to improve patient care.

A patient with multiple Swiss cheese aspect coronary lesions: optical coherence tomography to guide coronary angioplasty.

Although spontaneous recanalization of coronary thrombi has been reported pathologically, it is rarely recognized in clinical practice. We presented a rare case of recanalized thrombi of the right coronary artery and distal left anterior descending artery in a patient with an anterior ST segment elevation myocardial infarction treated with primary percutaneous intervention of the proximal left anterior descending artery. Optical coherence tomography aspect of right coronary artery was consistent with a 'Swiss cheese' appearance that represented recanalization of organized thrombi. Optical coherence tomography has been essential to discriminate the underlying mechanism and may provide useful information for an appropriate treatment approach.

Effect on Clinical Restenosis of an Ultra-Thin-Strut Bare Metal Cobalt-Chromium Stent Versus a Thin-Strut Stainless Steel Stent.

OBJECTIVES: To prospectively compare the impact of ultrathin-strut cobalt-chromium (Cro-Co) bare metal stent (BMS) versus thin-strut stainless steel (SS) BMS on clinically driven target lesion revascularization (TLR). BACKGROUND: Stent characteristics are an important determinant of restenosis. Thinner strut Cro-Co BMS is associated with a reduction of neointimal formation compared to SS BMS. The advantages of Cro-Co BMS in a real-world population is not clear. METHODS: Patients undergoing percutaneous coronary intervention (PCI) with BMS for any reason were enrolled. Patient with multi-vessel PCI, multi-lesions PCI, PCI of unprotected left main and coronary grafts were not excluded. They were divided in two groups according to stent type: Cro-Co or SS group. The primary endpoint was clinically driven TLR at follow-up. RESULTS: A total of 383 patients were enrolled: 222 in SS and 161 in Cro-Co group. During the follow-up, Cro-Co patients had a significantly lower occurrence of TLR compared to SS patients (1.9% vs 8.6%, P = 0.006). There were no significant differences for the composite endpoint of death, myocardial infarct, and stroke (4.9% in Cro-Co group vs 9.5% in SS group, P = 0.119). At multivariate analysis, the variables that were predictors of TLR were: use of SS stent (OR 4.43, P = 0.019) and diabetes (OR 2.84, P = 0.025). CONCLUSIONS: Ultra-thin strut Cro-Co BMS is associated with a significant reduction of clinically driven TLR in all comers population with any type of coronary disease complexity. (J Interven Cardiol 2016;29:300-310).

Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention.

AIMS: To evaluate the predictive value of high sensitivity (hs) C-reactive protein levels on long-term survival in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. METHODS AND RESULTS: We conducted a retrospective analysis of 758 STEMI patients (from January 2003 to December 2005), with STEMI onset <12 h and hs-C-reactive protein determination on admission. Patients were classified into four groups [I (hs-C-reactive protein < 0.48 mg/dL), II (hs-C-reactive protein > or = 0.48 to <1.2 mg/dL), III (hs-C-reactive protein > or = 1.2 to <3.1 mg/dL), IV (hs-C-reactive protein > or = 3.1 mg/dL)] according to quartiles of hs-C-reactive protein serum level. The IV quartile hs-C-reactive protein group had a higher incidence of in-hospital mortality and cumulative adverse events. At a mean follow-up of 724 +/- 376 days (range 0-1393), the IV quartile hs-C-reactive protein group showed lower estimated survival, lower estimated myocardial infarction-free survival and lower estimated event-free survival. At multivariable analysis hs-C-reactive protein appeared to be an independent predictor of long-term mortality (HR: 1.04, 95% CI: 1.01-1.07, P = 0.003), long-term mortality and re-infarction (HR: 1.03, 95% CI: 1.01-1.06, P = 0.008) and adverse events (HR: 1.03, 95% CI: 1.01-1.05, P = 0.03). CONCLUSION: Evaluation of hs-C-reactive protein on admission in STEMI patients undergoing primary PCI allows reliable risk stratification of these patients.

Usefulness of prehospital triage in patients with cardiogenic shock complicating ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

We investigated the impact of ambulance-based prehospital triage on treatment delay and all-cause mortality (in hospital and long term) in patients with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock referred for primary percutaneous coronary intervention in a prospectively collected registry. During the study period (January 2003 to December 2005), a total of 121 patients was referred for primary percutaneous coronary intervention at our intervention laboratory through 2 main triage groups: (1) after prehospital, ambulance-telemedicine-based triage (42 patients) and (2) by more conventional routes (79 patients) represented by the institutional S. Orsola-Malpighi hospital emergency department triage (44 patients) and spoke hospital triage (35 patients). Total ischemic time was shorter in the prehospital triage (142 minutes, range 106 to 187, vs 212 minutes, range 150 to 366, p = 0.003). Patients with prehospital triage showed a lower rate (29% vs 54%, p = 0.01) of severely depressed (

Clinical comparison of "normal-hours" vs "off-hours" percutaneous coronary interventions for ST-elevation myocardial infarction.

BACKGROUND: High mortality rates were reported in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary interventions (PPCI) "off-hours." The objective of this study was to evaluate this issue in a more recent population of patients with STEMI treated with PPCI in a high-volume tertiary center specifically dedicated to STEMI treatment. METHODS AND RESULTS: We analyzed in-hospital/1-year mortality among 985 consecutive patients with STEMI treated with PPCI between January 2003 and December 2005 in a high-volume (>1400 PCI/year) hub center in a STEMI provincial network organization during "normal-hours" (weekdays 08:00 am to 07:29 pm) and "off-hours" (weekdays 07:30 pm to 07:59 am and weekends). Most (61.2%) patients were treated during "off-hours". Clinical and angiographic characteristics of the "normal-hours" and "off-hours" groups were comparable (in both groups, glycoprotein IIb/IIIa were administered to approximately 80% patients). The off-hours group tended toward higher median (25th-75th percentiles) total ischemic time (199 [135-312] minutes vs 179 [126-285] minutes; P = .052). Median electrocardiogram-to-balloon time was less than 90 minutes in both groups. Despite 20 minutes longer median total ischemic time, patients who underwent PPCI during "off-hours" showed similar post-PPCI Thrombolysis In Myocardial Infarction 3 flow grade and mean left ventricular ejection fraction. No difference could be observed between the 2 groups in terms of in-hospital and 1-year mortality rates. CONCLUSION: This study provides evidence that the clinical effectiveness of "normal" and "off-hours" PPCI can be equivalent, at least when performed at a center specifically dedicated to STEMI treatment with frequent use of glycoprotein IIb/IIIa agents.

Randomized comparative trial of a thin-strut bare metal cobalt-chromium stent versus a sirolimus-eluting stent for coronary revascularization.

OBJECTIVES: To see whether use of a sirolimus-eluting stent (SES) is superior to a third-generation thin-strut, cobalt-chromium stent (CCS) in terms of in-segment late loss at 9 months in patients with symptomatic coronary artery disease. BACKGROUND: Stent-strut thickness has been shown to be strictly related with risk of in-stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick-strut bare metal control stents. METHODS: The primary outcome measure of this single-center, single-blind randomized comparative trial was 9-month in-segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3-mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher) or a CCS (Vision). RESULTS: In-segment late loss was significantly lower in the SES group (0.18 +/- 0.40 mm vs 0.58 +/- 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in-segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65). CONCLUSIONS: In patients with de-novo coronary lesions at medium risk of restenosis the anti-proliferative effect of SES is greater than that of a thin-strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.

Clinical impact of direct referral to primary percutaneous coronary intervention following pre-hospital diagnosis of ST-elevation myocardial infarction.

AIMS: Treatment delay is a powerful predictor of survival in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated effectiveness of pre-hospital diagnosis of STEMI with direct referral to PCI, alongside more conventional referral strategies. METHODS AND RESULTS: From January 2003 to December 2004, 658 STEMI patients were referred for primary PCI at our intervention laboratory. Three predefined referral routes were compared: (1) for patients within 90 min drive of the PCI centre, pre-hospital diagnosis and direct transportation (n=166), (2) diagnosis at the interventional hospital emergency department (n=316), (3) diagnosis at local hospitals before transportation (n = 176). Pre-hospital diagnosis was associated with more than 45 min reduction in treatment delay (P = 0.001). No significant difference in in-hospital mortality was apparent in the overall study population. In the cardiogenic shock subgroup (n = 80), pre-hospital diagnosis was associated with a two-thirds reduction in in-hospital mortality (P = 0.019); mortality was only 6.2% in shock patients who underwent PCI in < 2 h. CONCLUSION: This study shows that pre-hospital diagnosis can provide a reduction in primary PCI treatment delay, and suggests the hypothesis that this referral strategy might provide survival benefits to patients with cardiogenic shock.