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.

Layered plaque and plaque volume in patients with acute coronary syndromes.

BACKGROUND: Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated. METHODS: Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS. RESULTS: Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm3[114.2 mm3 to 275.0 mm3] vs. 119.3 mm3[68.9 mm3 to 185.5 mm3], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7-60.1%] vs. 53.7%[46.8-60.6%], p = 0.001), and plaque burden (86.5%[81.7-85.7%] vs. 82.6%[77.9-85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8-67.8%] vs. 57.5%[48.9-60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014). CONCLUSION: Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov , NCT01110538, NCT03479723, UMIN000041692.

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.

Urine alkalinisation to prevent contrast-induced acute kidney injury: the prospective, randomised, controlled, open-label TEATE trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is prognostically relevant in invasive cardiological and radiological procedures. The administration of sodium bicarbonate has controversial effects. It has been hypothesised that bicarbonate is ineffective when unable to achieve adequate urine alkalinisation. AIMS: We tested the hypothesis that alkaline urine status with oral or intravenous (i.v.) bicarbonate on top of hydration alone prevents CI-AKI. METHODS: In a prospective, randomised, parallel-group, open-label trial, we compared 1) saline hydration alone (n=81); 2) i.v. bicarbonate (n=82); and 3) oral bicarbonate (n=78), in patients with chronic kidney disease (CKD) scheduled for the intra-arterial administration of contrast medium. The primary endpoint was the incidence of CI-AKI according to alkaline urine status achieved immediately before angiography. Secondary endpoints were the mean change of urine pH up to the time of angiography and the incidence of CI-AKI in the three groups. RESULTS: The incidence of CI-AKI was not significantly different in the three treatment arms (20% in the hydration group, 21% in the oral bicarbonate group and 22% in the i.v. bicarbonate group; p=0.94). Patients achieving a pH >6 before angiography (n=145) had a significantly lower incidence of CI-AKI compared with the others (n=96; odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.25-0.90; p=0.023, primary study hypothesis). The proportion of patients achieving a pH >6 was higher in the i.v. and oral bicarbonate groups compared with hydration alone. CONCLUSIONS: Urinary pH before administration of contrast medium is an inverse correlate of CI-AKI incidence, and bicarbonate is superior to hydration alone in achieving urinary alkalinisation. Since, however, bicarbonate did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI (ClinicalTrials.gov: NCT02980003).

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.