Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS: A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. CONCLUSION: This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. TRIAL REGISTRATION: Registration of the study at clinicalTrials.gov (NCT03129503).

Cholesterol crystals at the culprit lesion in patients with acute coronary syndrome are associated with worse cardiovascular outcomes at two years follow up - results from the translational OPTICO-ACS study program.

BACKGROUND: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown. METHODS: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years. RESULTS: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040). CONCLUSIONS: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future.

[Hypercholesterolemia and cardiovascular risk]. / Hypercholesterinämie und kardiovaskuläres Risiko.

Pharmacological reduction of LDL-cholesterol (LDL-C) is a major treatment strategy in limiting atherosclerotic cardiovascular (ASCVD) risk. Statins remain the primary therapeutic cornerstone in ASCVD prevention. Furthermore, ezetimibe, bempedoic acid, and PCSK9 inhibition have recently also shown to reduce cardiovascular risk. Unfortunately, a treatment gap remains between guideline-recommended LDL-C goals and what is achieved in real-world practice. An important reason for this is the limited use of novel and effective non-statin lipid-lowering therapies. In order to achieve LDL-C treatment goals and, ultimately, reduction of cardiovascular events, a combination lipid-lowering therapy needs to be considered as the standard of care for patients at very high cardiovascular risk.

Left-ventricular unloading in extracorporeal cardiopulmonary resuscitation due to acute myocardial infarction - A multicenter study.

BACKGROUND: Guidelines advocate the use of extracorporeal cardio-pulmonary resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in selected patients with cardiac arrest. Effects of concomitant left-ventricular (LV) unloading with Impella® (ECMELLA) remain unclear. This is the first study to investigate whether treatment with ECMELLA was associated with improved outcomes in patients with refractory cardiac arrest caused by acute myocardial infarction (AMI). METHODS: This study was approved by the local ethical committee. Patients treated with ECMELLA at three centers between 2016 and 2021 were propensity score (PS)-matched to patients receiving VA-ECMO based on age, electrocardiogram rhythm, cardiac arrest location and Survival After Veno-Arterial ECMO (SAVE) score. Cox proportional-hazard and Poisson regression models were used to analyse 30-day mortality rate (primary outcome), hospital and intensive care unit (ICU) length of stay (LOS) (secondary outcomes). Sensitivity analyses on patient demographics and cardiac arrest parameters were performed. RESULTS: 95 adult patients were included in this study, out of whom 34 pairs of patients were PS-matched. ECMELLA treatment was associated with decreased 30-day mortality risk (Hazard Ratio [HR] 0.53 [95% Confidence Interval (CI) 0.31-0.91], P = 0.021), prolonged hospital (Incidence Rate Ratio (IRR) 1.71 [95% CI 1.50-1.95], P < 0.001) and ICU LOS (IRR 1.81 [95% CI 1.57-2.08], P < 0.001). LV ejection fraction significantly improved until ICU discharge in the ECMELLA group. Especially patients with prolonged low-flow time and high initial lactate benefited from additional LV unloading. CONCLUSIONS: LV unloading with Impella® concomitant to VA-ECMO therapy in patients with therapy-refractory cardiac arrest due to AMI was associated with improved patient outcomes.

Coexistence of calcified- and lipid-containing plaque components and their association with incidental rupture points in acute coronary syndrome-causing culprit lesions: results from the prospective OPTICO-ACS study.

AIMS: Rupture of the fibrous cap (RFC) represents the main pathophysiological mechanism causing acute coronary syndromes (ACS). Destabilization due to plaque biomechanics is considered to be importantly involved, exact mechanisms triggering plaque ruptures are, however, unknown. This study aims at characterizing the relation between plaque components and rupture points at ACS-causing culprit lesions in a large cohort of ACS-patients assessed by high-resolution intracoronary imaging. METHODS AND RESULTS: Within the prospective, multicentric OPTICO-ACS study program, the ACS-causing culprit plaques of 282 consecutive patients were investigated following a standardized optical coherence tomography (OCT) imaging protocol. Each pullback was assessed on a frame-by-frame basis for the presence of lipid components (LC), calcium components (CC), and coexistence of both LC and CC (LCC) by two independent OCT-core labs. Of the 282 ACS-patients, 204 patients (72.3%) presented with ACS caused by culprit lesions with rupture of the fibrous cap (RFC-ACS) and 27.7% patients had ACS caused by culprit lesions with intact fibrous cap (IFC-ACS). When comparing RFC-ACS to IFC-ACS, a preferential occurrence of all three plaque components (LC, CC, and LCC) in RFC-ACS became apparent (P < 0.001). Within ruptured culprit lesions, the zone straight at the rupture point [extended rupture zone (RZ)] was characterized by similar (24.7% vs. 24.0%; P = ns) calcium content when compared with the proximal and distal border of the culprit lesion [border zone (BZ)]. The RZ displayed a significantly higher amount of both, LC (100% vs. 69.8%; P < 0.001) and LCC (22.7% vs. 6.8%; P < 0.001), when compared with the BZ. The relative component increase towards the RZ was particularly evident for LCC (+233.8%), while LC showed only a modest increase (+43.3%). CONCLUSIONS: Calcified- and lipid-containing components characterize ruptured fibrous cap ACS-causing culprit lesions. Their coexistence is accelerated directly at the ruptured point, suggesting a pathophysiological contribution in the development of RFC-ACS.

Prognostic Impact of Pancoronary Quantitative Flow Ratio Assessment in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes.

BACKGROUND: Quantitative flow ratio (QFR) has been introduced as a novel angiography-based modality for fast hemodynamic assessment of coronary artery lesions and validated against fractional flow reserve. This study sought to define the prognostic role of pancoronary QFR assessment in patients with acute coronary syndrome (ACS) including postinterventional culprit and nonculprit vessels. METHODS: In a total of 792 patients with ACS (48.6% ST-segment-elevation ACS and 51.4% non-ST-segment-elevation ACS), QFR analyses of postinterventional culprit (n=792 vessels) and nonculprit vessels (n=1231 vessels) were post hoc performed by investigators blinded to clinical outcomes. The follow-up comprised of major adverse cardiovascular events, including all-cause mortality, nonfatal myocardial infarction, and ischemia-driven coronary revascularization within 2 years after the index ACS event. RESULTS: Major adverse cardiovascular events as composite end point occurred in 99 patients (12.5%). QFR with an optimal cutoff value of 0.89 for postinterventional culprit vessels and 0.85 for nonculprit vessels emerged as independent predictor of major adverse cardiovascular events after ACS (nonculprit arteries: adjusted odds ratio, 3.78 [95% CI, 2.21-6.45], P<0.001 and postpercutaneous coronary intervention culprit arteries: adjusted odds ratio, 3.60 [95% CI, 2.09-6.20], P<0.001). CONCLUSIONS: The present study for the first time demonstrates the prognostic implications of a pancoronary angiography-based functional lesion assessment in patients with ACS. Hence, QFR offers a novel tool to advance risk stratification and guide therapeutic management after ACS.

[New Lipid-lowering Agents]. / Neue lipidsenkende Substanzen.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality. The fact that elevated levels of low-density lipoprotein-cholesterol (LDL-C) play a causal role in the development of ASCVD is now well accepted, given the results of numerous epidemiological and genetic studies, as well as randomized controlled clinical trials. Statins have become a primary therapeutic cornerstone in ASCVD prevention since they have been shown to reduce CV events by reducing levels of LDL-C. But despite the proven efficacy and safety of statin therapy, several aspects indicate a substantial need for additional or alternative LDL-C lowering therapies. These aspects include not only a high variability in individual response to therapy, but also possible side effects, potentially reducing adherence to treatment. Most importantly, an elevated risk for cardiovascular (CV) events remains in a large proportion of high-risk patients, especially in those with persistent elevation of LDL-C levels despite a maximum tolerated dose of statin therapy. Also, large clinical trials currently investigate a potential CV benefit of drug therapies targeting elevated levels of triglycerides and lipoprotein (a), respectively.

Impact of real-time angiographic co-registered optical coherence tomography on percutaneous coronary intervention: the OPTICO-integration II trial.

AIMS: Longitudinal geographic mismatch (LGM) as well as edge dissections are associated with an increased risk of adverse events after percutaneous coronary intervention (PCI). Recently, a novel system of real-time optical coherence tomography (OCT) with angiographic co-registration (ACR) became available and allows matched integration of cross-sectional OCT images to angiography. The OPTICO-integration II trial sought to assess the impact of ACR for PCI planning on the risk of LGM and edge dissections. METHODS: A total of 84 patients were prospectively randomized to ACR-guided PCI, OCT-guided PCI (without co-registration), and angiography-guided PCI. Primary endpoint was a composite of major edge dissection and/or LGM as assessed by post-PCI OCT. RESULTS: The primary endpoint was significantly reduced in ACR-guided PCI (4.2%) as compared to OCT-guided PCI (19.1%; p = 0.03) and angiography-guided PCI (25.5%; p < 0.01). Rates of LGM were 4.2%, 17.0%, and 22.9% in the ACR-guided PCI, in the OCT-guided PCI, and the angiography-guided PCI groups, respectively (ACR vs. OCT p = 0.04; ACR vs. angiography p = 0.04). The number of major edge dissections was low and without significant differences among the study groups (0% vs. 2.1% vs. 4.3%). CONCLUSION: This study for the first time demonstrates superiority of ACR-guided PCI over OCT- and angiography-guided PCI in reducing the composite endpoint of major edge dissection and LGM, which was meanly driven by a reduction of LGM.

Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran).

PURPOSE OF REVIEW: The aim of low-density lipoprotein-cholesterol (LDL-C) lowering therapies is to safely achieve a consistent and long-term reduction in exposure of the vasculature to atherogenic lipoproteins in order to reduce the risk of atherosclerotic cardiovascular (CV) disease and the associated CV events, such as myocardial infarctions and ischemic strokes. This review summarizes the concept and clinical development of a novel molecular approach to efficiently lower LDL-C, a synthetic small interfering ribonucleic acid (siRNA)-inclisiran-directed against proprotein convertase subtilisin-kexin type 9 (PCSK9). RECENT FINDINGS: The understanding of genes regulating atherogenic lipoproteins and their causal role in the development of atherosclerotic CV disease has substantially advanced over the past years. This has opened the possibility for development of molecular therapies targeting these atherogenic lipoproteins, in particular by RNA-targeted treatment approaches. The most advanced clinical development program is the siRNA-treatment targeting PCSK9 (inclisiran), involving more than 4000 patients in clinical studies. Phase 1 and 2 studies have identified the dose of 300 mg inclisiran for efficient LDL-C lowering. Most recently, three phase 3 studies demonstrated that a regimen of inclisiran every 6 months was feasible and reduced LDL-C by approximately 50% in patients at high or very high CV risk or with familial hypercholesterolemia. Adverse events were similar in the inclisiran and the placebo groups, except for more frequent transient injection site reactions with inclisiran than with placebo. siRNA therapy targeting PCSK9 (inclisiran) applied twice a year efficiently reduced LDL-C by approximately 50% and was safe in recent phase 3 studies. The effects of this treatment on CV outcome are currently further assessed in a large ongoing CV outcome trial.

A randomised comparison of monoplane versus biplane fluoroscopy in patients undergoing percutaneous coronary intervention: the RAMBO trial.

AIMS: Interventional cardiologists are exposed to substantial occupational ionising radiation. This study sought to investigate differences in radiation exposure in biplane versus monoplane coronary angiography and percutaneous coronary interventions (PCI). METHODS AND RESULTS: RAMBO (RAdiation exposure in Monoplane versus Biplane cOronary angiography and interventions) was a prospective, randomised, two-arm, single-centre, open-label trial, enrolling a total of 430 patients undergoing coronary angiography. Patients were randomly assigned to biplane or monoplane imaging. The primary efficacy measure, the operator radiation dose at the level of the left arm as measured by a wearable electronic dosimeter, was significantly higher in the biplane as compared to the monoplane group (4 [1-13] µSv vs 2 [0-6.8] µSv, p<0.001). The dose area product was 11,955 (7,095-18,246) mGy*cm2 and 8,349 (5,851-14,159) mGy*cm2 in the biplane and the monoplane groups, respectively (p<0.001). While fluoroscopy time did not differ between the groups (p=0.89), the amount of contrast medium was lower with biplane as compared with monoplane imaging (p<0.001). CONCLUSIONS: Biplane imaging for coronary angiography and PCI is related to an increased radiation exposure for the interventional cardiologist as compared with monoplane imaging. Monoplane imaging should be considered for advanced radioprotection in cardiac catheterisation, with biplane imaging used for selected cases only.

Association of left ventricular end-diastolic pressure with mortality in patients undergoing percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVES: This study sought to investigate the relation between left ventricular end-diastolic pressure (LVEDP) and outcomes in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). BACKGROUND: Risk stratification in ACS patients is important. Data on the role of LVEDP in the prognostication of ACS patients are scarce. METHODS: A total of 1,410 patients undergoing PCI for ACS and with available data on LVEDP were divided according to LVEDP tertiles (lowest tertile: ≤13 mmHg, intermediate tertile: 14-20 mmHg, and highest tertile: >20 mmHg). The primary endpoint was all-cause mortality at a median follow-up of 246 [28-848] days. RESULTS: Median LVEDP was 16 (11-22) mmHg. All-cause mortality was 2.8%, 4.5%, and 15.0% in the lowest, the intermediate, and the highest LVEDP tertile groups (p < .001), respectively. Belonging to the highest LVEDP tertile was associated with an increased risk of all-cause mortality (adjusted hazard ratio [HR] = 2.66, 95% confidence interval [CI] [1.30, 5.47], p = .008). By receiver operating characteristic curve analysis, the optimal cut-off value for predicting all-cause mortality was 20 mmHg (sensitivity 68.3%, specificity 72.5%). There was no differential effect of LVEDP on mortality in patients with and without LV dysfunction (interaction p = .23) or ST-elevation myocardial infarction as index ACS event (interaction p = .86). CONCLUSIONS: In patients undergoing PCI for ACS, LVEDP was independently related with mortality. Hence, LVEDP should be incorporated into early risk stratification and clinical decision making of ACS patients.

Cohort profile: role of lipoproteins in cardiovascular disease-the LipidCardio study.

PURPOSE: The LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. In particular, the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease (CVD) will be a main focus. PARTICIPANTS: 1005 individuals aged 21 years and older undergoing cardiac catheterisation during 17 months at a tertiary academic cardiology centre were enrolled (troponin-positive acute coronary syndrome was exclusion criterion). The baseline data not only contain detailed phenotyping, broad biochemical parameters, genetic data, but also standardised personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, among others. Blood samples were stored in a biobank for future analyses. FINDINGS TO DATE: The mean age of the participants at enrolment was 70.9±11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of CVD than participants without CAD.About 20% of patients had lipoprotein(a) (Lp(a)) concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared with participants in quintiles 1-4 (crude OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in the LPA gene (rs10455872, rs3798220 and rs186696265) and the APOE gene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank. FUTURE PLANS: Mortality information will be obtained in 2 year intervals. Follow-up phone interviews will be conducted at 3 and 6 years after enrolment. We seek to cooperate with other researchers, for example, by sharing data and biobank samples.

Is There a Need to Revise Goals in the Management of Dyslipidemias?

PURPOSE OF REVIEW: Current guidelines on the management of patients with dyslipidemias recommend specific risk-dependent low-density lipoprotein cholesterol (LDL-C) treatment goals. Recently, several randomized clinical trials have investigated further lowering of LDL-C in addition to statin therapy using novel therapeutic approaches and examined their effects on cardiovascular (CV) risk. This review summarizes newly available data on efficacy and safety of lowering LDL-C beyond statin therapy and below current treatment targets. RECENT FINDINGS: In patients at very high risk for CV events, a significant residual risk remains when failing to achieve significant LDL-C reduction on maximally tolerated statin therapy alone. Further lowering of LDL-C, even beyond current treatment targets, has been shown to be safe and was associated with a further reduced CV risk reduction. The relative risk reduction per change in LDL-C levels has been observed to be consistent even in patient populations achieving extremely low levels of LDL-C. In patients at very high CV risk, further lowering of LDL-C beyond statin therapy and present treatment targets has been observed to further reduce CV risk, which may be foremost relevant for patients at a particular high absolute CV risk, e.g., for patients with progressive and/or very extensive coronary disease.

Effect of Physical Disability on Mortality in Elderly Patients of ≥80 Years of Age Undergoing Percutaneous Coronary Intervention.

Functional decrease has been linked with adverse events in different clinical contexts. The predictive role of activity of daily living status as assessed by the Barthel index (BI) in elderly patients who underwent percutaneous coronary intervention (PCI) has not been investigated, yet. In this study, a total of 616 patients (≥80 years) who underwent PCI between January 2009 and December 2014 and with available activity of daily living data on admission were stratified according to BI (low BI <85, intermediate BI 85 to 95, high BI 100). The primary end point was all-cause mortality at a total follow-up of 442 days (interquartile range 47 to 1243). Of the 616 patients, 178 (29%), 128 (21%), and 310 (50%) were in the low, the intermediate, and the high BI groups, respectively. All-cause mortality was 10%, 13%, and 5% in the low, the intermediate, and the high BI groups, respectively (log-rank p <0.001). Belonging to the high BI group was associated with a reduced risk of all-cause mortality (hazard ratio 0.35, 95% confidence interval 0.18 to 0.69, p = 0.002), and associations remained significant after multivariable adjustments (adjusted hazard ratio 0.34, 95% confidence interval 0.13 to 0.93, p = 0.04). Functional capacity was identified as independent predictor of survival in a large cohort of patients who underwent PCI. In conclusion, activities of daily living should be incorporated into the risk stratification of elderly patients with coronary artery disease.

Revival of transcatheter PFO closure: A meta-analysis of randomized controlled trials - impact of shunt size and age.

BACKGROUND: Transcatheter foramen ovale closure (TPC) has emerged as a potential treatment option for patients with cryptogenic strokes and persistent foramen ovale (PFO). However, previous randomized controlled trials could hardly demonstrate any benefit compared to medical treatment (Med-Tx). Recently new data have become available which may change current practice of transcatheter PFO closure. METHODS: A systematic review and meta-analysis comparing TPC and Med-Tx based on all available multicentric randomized controlled trials was performed. The primary outcome of interest was the recurrence of stroke in both groups. RESULTS: Five studies met the inclusion criteria with 1829 patients in the TPC and 1622 in the Med-Tx group. The median follow-up was 4 years. In the intention-to-treat analysis we found a statistically significant relative risk reduction in recurrence of strokes in the TPC group compared to the Med-Tx group (pooled hazard ratio (HR): 0.32; 95% CI: 0.13-0.8; P = .018). Excluding one study due to potential publication bias resulted in a pooled HR of 0.48 (95% CI: 0.25-0.91, P = .024). Patients younger than 45 years of age (pooled HR: 0.35; 95% CI: 0.16-0.75; P = .007) and those with moderate to severe shunt (pooled HR: 0.28; 95% CI: 0.14-0.55; P < .001) were more likely to benefit from closure. CONCLUSION: According to our meta-analysis TPC plus antiplatelets was superior in terms of stroke prevention when compared to Med-Tx. Furthermore, patients with moderate to severe shunts and those younger than 45 years of age were found to benefit most from TPC.

Effective low-density lipoprotein-lowering therapy: Implementation in clinical practice.

Although age-adjusted mortality of coronary heart disease has been successfully reduced over recent years, coronary heart disease still represents a leading cause of death and morbidity, in particular in patients at very high cardiovascular risk. Dyslipidaemia plays a major and causal role in the development and clinical progression of coronary heart disease. At present, low-density lipoprotein cholesterol represents the primary target of lipid-directed therapies for the prevention of cardiovascular disease and events. The new European guidelines recommend intensive statin therapy and the possible addition of ezetimibe to reduce low-density lipoprotein cholesterol to a goal of less than 1.8 mmol/L (<70 mg/dL) or by at least 50% if the baseline low-density lipoprotein cholesterol is between 1.8 and 3.5 mmol/L (70-135 mg/dL) in patients at very high cardiovascular risk. Also, the new European guidelines now mention the potential use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in very high-risk patients with persistently high levels of low-density lipoprotein cholesterol despite maximally tolerated statin treatment in combination with ezetimibe or in patients with statin intolerance. A recent European consensus document discusses the practical clinical use of PCSK9 inhibitors and provides more detailed recommendations. However, despite the overwhelming scientific evidence of the beneficial effects of lipid-lowering therapies, a large proportion of patients at very high cardiovascular risk are not treated according to the current European guideline recommendations. Reinforcing lipid-lowering therapies provides an excellent chance effectively to reduce morbidity and mortality from coronary heart disease.

Diastolic pressure-volume quotient (DPVQ) as a novel echocardiographic index for estimation of LV stiffness in HFpEF.

BACKGROUND: End-diastolic pressure-volume relationship and LV stiffness, key parameter for diagnosing diastolic dysfunction within Heart failure with preserved ejection fraction (HFpEF) patients, can be directly obtained only by invasive pressure-volume (PV) measurements. Therefore, we aimed to establish diastolic pressure-volume quotient (DPVQ), as a new non-invasive parameter for estimation of LV stiffness in HFpEF obtained by 3D echocardiography (3DE) and tissue Doppler imaging. METHODS: Twenty-three HFpEF patients with suspected diastolic dysfunction, scheduled for invasive pressure-volume loop analyses obtained by conductance catheterization were included. PV loop measurements were compared with simultaneous 3DE full-volume recordings of the LV and tissue Doppler measurements for LV diastolic function. LV filling index E/E' was used for estimation of diastolic pressure. Single-beat method was performed to calculate LV stiffness constant (ß SB). RESULTS: Fourteen of twenty-three patients showed increased and 9/23 revealed normal LV stiffness ß. End-diastolic, end-systolic and stroke volume obtained by 3DE correlated with those from PV loop analysis (r = 0.63, r = 0.57 and r = 0.71, respectively). Estimated diastolic pressure and DPVQ correlated with invasive measurements (r = 0.81 and r = 0.91, both p < 0.001). Accordingly, calculated stiffness constant ß SB revealed a significant correlation with invasive determined stiffness coefficient ß (r = 0.73, p < 0.001). DPVQ and ß SB correlated with NT-proBNP plasma level (r = 0.67 and r = 0.58, both, p < 0.001). CONCLUSION: 3D echocardiography allows accurate non-invasive measurements of diastolic pressure-volume quotient which correlates with invasive determined LV stiffness in HFpEF.