Current spectrum and outcomes of infarct-related cardiogenic shock: insights from the CULPRIT-SHOCK registry and randomized controlled trial.

AIMS: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry. METHODS AND RESULTS: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0%. 54.2% of the patients had cardiac arrest before admission. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-vessel CAD (38.6%), respectively. Mechanical complications were rare (21/1008; 2.1%) but associated with a high mortality of 66.7% after 1 year. CONCLUSION: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS.

Type 2 Myocardial Infarction and Long-Term Mortality Risk Factors: A Retrospective Cohort Study.

INTRODUCTION: In-hospital risk factors for type 1 myocardial infarction (MI) have been extensively investigated, but risk factors for type 2 MI are still emerging. Moreover, type 2 MI remains an underdiagnosed and under-researched condition. Our aim was to assess survival rates after type 2 MI and to analyze the risk factors for patient prognosis after hospitalization. METHODS: We conducted a retrospective database analysis of patients with MI diagnosis who were treated in Vilnius University Hospital Santaros Klinikos. A total of 6495 patients with the diagnosis of MI were screened. The primary study endpoint was long-term all-cause mortality. The predictive value of laboratory tests was estimated including blood hemoglobin, D dimer, creatinine, brain natriuretic peptide (BNP), C-reactive protein (CRP), and troponin levels. RESULTS: Out of all the patients diagnosed with MI there were 129 cases of type 2 MI (1.98%). Death rate almost doubled from 19.4% at 6 months to 36.4% after 2 years of follow-up. Higher age and impaired kidney function were risk factors for death both during hospitalization and after 2 years of follow-up. Lower hemoglobin (116.6 vs. 98.9 g/L), higher creatinine (90 vs. 161.9 µmol/L), higher CRP (31.4 vs. 63.3 mg/l), BNP (707.9 vs. 2999.3 ng/L), and lower left ventricle ejection fraction were all predictors of worse survival after 2 years of follow-up. Preventive medication during hospitalization can decrease the mortality risk: angiotensin-converting enzyme inhibitor (ACEi) (HR 0.485, 95% CI 0.286-0.820) and statins (HR 0.549, 95% CI 0.335-0.900). No significant influence was found for beta blockers (HR 0.662, 95% CI 0.371-1.181) or aspirin (HR 0.901, 95% CI 0.527-1.539). CONCLUSIONS: There is significant underdiagnosis of type 2 MI (1.98% out of all MIs). If the patient is prescribed a preventive medication like ACEi or statins, the mortality risk is lower. Increased awareness of elevation of laboratory results could help to improve the treatment of these patients and identify the most vulnerable groups.

Extracorporeal Life Support for Cardiogenic Shock in Octogenarians: Single Center Experience.

BACKGROUND: The age limit for the use of extracorporeal membrane oxygenation (ECMO) support for post-cardiotomy cardiac failure is not defined. The aim of the study was to evaluate the outcomes of octogenarians supported with ECMO due to cardiogenic shock. METHODS: A retrospective review of consecutive elderly patients supported with ECMO during a 13-year period in a tertiary care center. Patient's demographic variables, comorbidities, perioperative data and outcomes were collected from patient medical records. Data of octogenarian patients were compared with the septuagenarian group. The main outcomes of the study was in hospital mortality, 6-month survival and 1-year survival after hospital discharge and discharge options. Multivariate logistic regression analysis was performed to identify the factors associated with hospital survival. RESULTS: Eleven patients (18.3%) in the elderly group were octogenarians (aged 80 years or above), and forty-nine (81.7%) were septuagenarians (aged 70-79 years). There were no differences except age in demographic and preoperative variables between groups. Pre ECMO SAVE, SOFA, SAPS-II and inotropic scores were significantly higher in septuagenarians than octogenarians. There was no statistically significant difference in hospital mortality, 6-month survival, 1 year survival or discharge options between groups. CONCLUSIONS: ECMO could be successfully used in selected octogenarian patients undergoing cardiac surgery to support a failing heart. An early decision to initiate ECMO therapy in elderly post-cardiotomy shock patients is associated with favorable outcomes.

Care of patients with ST-elevation myocardial infarction: an international analysis of quality indicators in the acute coronary syndrome STEMI Registry of the EURObservational Research Programme and ACVC and EAPCI Associations of the European Society of Cardiology in 11 462 patients.

AIMS: To use quality indicators to study the management of ST-segment elevation myocardial infarction (STEMI) in different regions. METHODS AND RESULTS: Prospective cohort study of STEMI within 24 h of symptom onset (11 462 patients, 196 centres, 26 European Society of Cardiology members, and 3 affiliated countries). The median delay between arrival at a percutaneous cardiovascular intervention (PCI) centre and primary PCI was 40 min (interquartile range 20-74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 min. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4 to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented left ventricular ejection fraction ≤40%, 84.0% were discharged on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and 88.7% were discharged on beta-blockers. CONCLUSION: Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge.

Sudden cardiac death in patients with coronary heart disease and antemortem alcohol intake: A STROBE - compliant retrospective study.

The present study was aimed to assess the prevalence and possible causal relationship of alcohol intake prior to a sudden cardiac death event in patients with coronary artery disease. The retrospective research was performed at the Vilnius branch of The State Forensic Medicine Service. The autopsy protocols for five years were analyzed and the cases of sudden cardiac death were selected, when the determined cause of death was Coronary Heart Disease (CHD), a forensic autopsy and toxicological blood and urine test had been performed. Cases of the sudden death of non-cardiac origin, cases of cardiomyopathy of various origins, and cases of acute cardiac arrest of unspecified origin were excluded. The data collected was processed using R software. The study sample consisted of 2133 cases. 706 (33%) CHD cases were alcohol positive. Males and young age CHD victims were more likely to find alcohol than females (72% vs. 28%, respectively, P < .001). The mean blood alcohol concentration of the sample was 1.37 ‰± 1.01, urine's 1.73‰ ± 1.29. Alcohol was more commonly found during the winter months and the holidays. Deaths in alcohol-positive individuals were more common in the alcohol elimination phase with hemodynamically insignificant coronary artery stenosis (up to 50% of arterial lumen). Nearly every third CHD victim in Lithuania who experienced sudden death also had signs of antemortem alcohol consumption.

High-Sensitivity Cardiac Troponin Impact on the Differential Diagnosis of Non-ST Segment Elevation Coronary Syndromes-Is It Helping?

Background and Objectives: Increased levels of high-sensitivity cardiac troponin (hs-cTn) are the main criteria that differentiate non-ST segment elevation myocardial infarction (NSTEMI) from unstable angina (UA). How are these implemented in clinical practices? This study aims to detect cases of misdiagnosed UA instead of NSTEMI. Materials and Methods: We analysed discharge summaries of 840 patients admitted to Vilnius University Hospital Santaros Klinikos with the diagnosis of UA in 2017-2018. We retrospectively checked symptoms, levels of hs-cTn, coronary angiography and electrocardiogram changes with an aim to differentiate UA and type 1 NSTEMI, according to the Fourth Universal Definition of Myocardial Infarction. We excluded patients with missing hs-cTn levels or coronary angiography. Results: We found that 46.71% (n = 334) of patients met the diagnostic criteria of UA according to the Fourth Universal Definition, whereas 19.16% of patients (n = 137) could have been diagnosed with type 1 NSTEMI instead of UA. In the group of patients who could be reclassified to type 1 NSTEMI, the median level of hs-cTn was 184.32 [226.15] ng/L on admission. The median of the lowest level during the hospitalization was 114.0 [207.4] ng/L. Median highest-304.0 [257.6] ng/L. Myocardial infarction with non-obstructive coronary arteries could have been diagnosed in 3.36% (n = 24) of patients. Conclusions: Only less than half of patients met the diagnostic UA criteria. Almost one-fifth of patients with a diagnosis of UA could be reclassified to type 1 NSTEMI.

Chest pain in the emergency department: From score to core-A prospective clinical study.

High-sensitivity troponin assay brought new challenges as we detect elevated concentration in many other diseases, and it became difficult to distinguish the real cause of this elevation. In this notion, diagnosis of acute coronary syndrome (ACS) remains a challenge in emergency department (ED). We aim to examine different approaches for rule-in and rule-out of ACS using risk scores, copeptin, and coronary computed tomography angiography (CCTA). A prospective observational study was designed to evaluate chest pain patients. Consecutive adult patients admitted to the ED with a chief complaint of chest pain due to any cause were included. All patients were followed-up for 6 months after discharge for major adverse cardiovascular events and readmissions. Admission data, ED processes, and diagnoses were analyzed. One hundred forty-six patients were included, average age was 63 ± 13.4 years, and 95 (65.1%) were male. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk factors, Troponin (HEART) scores showed good prognostic abilities, but HEART combination with copeptin improves diagnoses of myocardial infarction (area under the curve [AUC] 0.764 vs AUC 0.864 P = .0008). Patients with elevated copeptin were older, had higher risk scores, and were more likely to be admitted to hospital and diagnosed with ACS in ED. For copeptin, AUC was 0.715 (95% confidence interval 0.629-0.803), and for combination with troponin, AUC of 0.770 (0.703-0.855) did not improve rule-in of myocardial infarction. High-sensitivity troponin I assay alongside prior stroke, history of carotid stenosis, dyslipidemia, use of diuretics, and electrocardiogram changes (left bundle branch block or ST depression) are good predictors of myocardial infarction (χ² = 52.29, AUC = 0.875 [0.813-0.937], P < .001). The regression analysis showed that combination of copeptin and CCTA without significant stenosis can be used for ACS rule-out (χ² = 26.36, P < .001, AUC = 0.772 [0.681-0.863], negative predictive value of 96.25%). For rule-in of ACS, practitioner should consider not only scores for risk stratification but carefully analyze medical history and nonspecific electrocardiogram changes and even with normal troponin results, we strongly suggest thorough evaluation in chest pain unit. For rule-out of ACS combination of copeptin and CCTA holds great potential.

Collateral effect of the COVID-19 pandemic on cardiology service provision and cardiovascular mortality in a population-based study: COVID-COR-LT.

BACKGROUND: Collateral damage of the COVID-19 pandemic on cardiovascular health is increasingly studied. This is a population-based study addressing multiple aspects of cardiovascular care during the pandemic in a country of Lithuania, in which pandemic waves were significantly different. METHODS: Data on cardiology outpatient care, hospitalizations and cardiovascular mortality in 2019 and 2020 were collected from Lithuanian nationwide administrative databases and registries. Weekly data and aggregated numbers of corresponding 6-week phases were analyzed comparing the numbers between 2019 and 2020. Age, sex and regional subgroup analysis was performed. RESULTS: Both cardiovascular outpatient care visits and hospitalizations decreased dramatically in 2020 compared to 2019 with a peak reduction (up to - 60% for both) during the first pandemic wave in spring of 2020. Simultaneously, cardiovascular mortality was much higher in 2020, with a pronounced peak at the end of the year compared to 2019 (up to 46%). The increase was even more staggering when analyzing home deaths, which rose up to 91% by the end of 2020. Notable differences between age groups, regions and sexes were documented. CONCLUSION: A profound indirect damage of COVID-19 pandemic on cardiovascular care was observed in this study, with striking decreases in cardiovascular care provision and concurrent increase in cardiovascular mortality, both overall and, even more dramatically, at home. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05021575 (registration date 25-08-2021, retrospectively registered).

Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in heart failure: the GALACTIC-HF trial.

AIMS: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil. METHODS AND RESULTS: GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF. CONCLUSION: Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.Clinical Trial Registration: NCT02929329.

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study.

Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=-0.303, p=0.013) and non-invasively (native T1; r=-0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Randomized Pilot Trial on Optimal Treatment Strategy, Myocardial Changes, and Prognosis of Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains an unresolved challenge. Many different diagnostic approaches are often required to diagnose, confirm, and evaluate MINOCA. The prevalence can be as high as 13% of all acute myocardial infarction patients, indicating that this condition is not rare. At this time, there have been no completed randomized clinical trials involving MINOCA patients, and a better understanding of the mechanisms and management of these patients is important. This exploratory analysis seeks to find possible etiologic factors, the value of novel biomarkers, and the effect of different treatment strategies in patients with MINOCA. METHODS: This prospective randomized pilot trial will include 150 patients with MINOCA. A thorough clinical, laboratory, and imaging evaluation will be performed, including novel biomarkers and modern imaging techniques (heart magnetic resonance imaging and noninvasive testing). The duration of the enrollment is 18 months, and duration of the follow-up is 12 months from the enrollment of the first patient. RESULTS: The trial is registered under www.clinicaltrials.gov: NCT04538924. The study is currently recruiting participants. CONCLUSIONS: Because MINOCA is not a benign disease, the results of the current investigation could inform future diagnostic and therapeutic strategies and enhance the understanding of MINOCA patients.

Increase of Myocardial Ischemia Time and Short-Term Prognosis of Patients with Acute Myocardial Infarction during the First COVID-19 Pandemic Wave.

Background and objectives: early reports showed a decrease in admission rates and an increase in mortality of patients with acute myocardial infarction (AMI) during the first wave of COVID-19 pandemic. We sought to investigate whether the COVID-19 pandemic and associated lockdown had an impact on the ischemia time and prognosis of patients suffering from AMI in the settings of low COVID-19 burden. Materials and Methods: we conducted a retrospective data analysis from a tertiary center in Lithuania of 818 patients with AMI. Data were collected from 1 March to 30 June in 2020 during the peri-lockdown period (2020 group; n = 278) and compared to the same period last year (2019 group; n = 326). The primary study endpoint was all-cause mortality during 3 months of follow-up. Secondary endpoints were heart failure severity (Killip class) on admission and ischemia time in patients with acute ST segment elevation myocardial infarction (STEMI). Results: there was a reduction of 14.7% in admission rate for acute myocardial infarction (AMI) during the peri-lockdown period. The 3-month mortality rate did not differ significantly (6.9% in 2020 vs. 10.5% in 2019, p = 0.341 for STEMI patients; 5.3% in 2020 vs. 2.6% in 2019, p = 0.374 for patients with acute myocardial infarction without ST segment elevation (NSTEMI)). More STEMI patients presented with Killip IV class in 2019 (13.5% vs. 5.5%, p = 0.043, respectively). There was an increase of door-to-PCI time (54.0 [42.0-86.0] in 2019; 63.5 [48.3-97.5] in 2020, p = 0.018) and first medical contact (FMC)-to-PCI time (101.0 [82.5-120.8] in 2019; 115 [97.0-154.5] in 2020, p = 0.01) during the pandemic period. Conclusions: There was a 14.7% reduction of admissions for AMI during the first wave of COVID-19. FMC-to-PCI time increased during the peri-lockdown period, however, it did not translate into worse survival during follow-up.

Impact of Center Volume on Outcomes in Myocardial Infarction Complicated by Cardiogenic Shock: A CULPRIT-SHOCK Substudy.

Background Little is known about the impact of center volume on outcomes in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to investigate the association between center volume, treatment strategies, and subsequent outcome in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results In this subanalysis of the randomized CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, study sites were categorized based on the annual volume of acute myocardial infarction complicated by cardiogenic shock into low-/intermediate-/high-volume centers (<50; 50-100; and >100 cases/y). Subjects from the study/compulsory registry with available volume data were included. Baseline/procedural characteristics, overall treatment, and 1-year all-cause mortality were compared across categories. n=1032 patients were included in this study (537 treated at low-volume, 240 at intermediate-volume, and 255 at high-volume centers). Baseline risk profile of patients across the volume categories was similar, although high-volume centers included a larger number of older patients. Low-/intermediate-volume centers had more resuscitated patients (57.5%/58.8% versus 42.2%; P<0.01), and more patients on mechanical ventilation in comparison to high-volume centers. There were no differences in reperfusion success despite considerable differences in adjunctive pharmacological/device therapies. There was no difference in 1-year all-cause mortality across volume categories (51.1% versus 56.5% versus 54.4%; P=0.34). Conclusions In this study of patients with acute myocardial infarction complicated by cardiogenic shock, considerable differences in adjunctive medical and mechanical support therapies were observed. However, we could not detect an impact of center volume on reperfusion success or mortality.

Review of New Clinical Aspects of Cardiac Pathology in Patients with COVID-19 Infection.

SUMMARY BACKGROUND: COVID-19 disease is a huge burden for society and healthcare specialists. As more information is gathered about this new disease, it becomes clear that it affects not only respiratory, but also cardiovascular system. MATERIALS AND METHODS: The aim of this review is to analyse the information about myocardial injury caused by COVID-19 and overview treatment options for these patients in publications which were published in the last 5 years. The data for this overview were collected in the PubMed database. Full-text articles were used for analysis when their title, summary, or keywords matched the purpose of the review. Only publications published in English that appeared in the last 5 years were analysed. For the analysis 14 publications were selected and analysed. CONCLUSION: COVID-19 infection could mimic ST-elevation myocardial infarction and it is crucial to differentiate the main cause and choose the appropriate treatment. Cardiovascular complications are related with poorer prognosis and higher mortality. This should be thoroughly considered by the healthcare specialists in order to choose appropriate treatment strategy. Patients with acute coronary syndrome (ACS) due to plaque rupture should receive dual antiplatelet therapy and full-dose anticoagulation if it is not contraindicated. Therefore, priority should be given to the acute coronary syndrome given the low evidence of new antiviral treatment effectiveness. Number of agents which are under investigation for COVID-19 may have interactions with oral antiplatelet drugs. Selected patients could receive immunosuppressive treatment as well as extracorporeal membrane oxygenation as a bridge to recovery.

Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

AIMS: The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion. CONCLUSIONS: The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.

Long-Term Effects of Renal Artery Denervation.

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3-12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients' antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range-IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was -11 ± 25 mmHg (95% CI, -20 to -2; p < 0.001), while office systolic BP reduced by -7 ± 23 mmHg (95%CI, -24 to -1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1-5 pill group: 8.1 ± 1.6 m/s; 6-10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.

Clinical Outcomes According to ECG Presentations in Infarct-Related Cardiogenic Shock in the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock Trial.

BACKGROUND: The impact of ECG presentations of acute myocardial infarction (AMI) in cardiogenic shock is unknown. RESEARCH QUESTION: In myocardial infarction with cardiogenic shock, is there a difference in the outcomes and effect of revascularization strategies between non-ST-segment elevation myocardial infarction (NSTEMI) and left bundle branch block myocardial infarction (LBBBMI) vs ST-segment elevation myocardial infarction (STEMI)? STUDY DESIGN AND METHODS: Cardiogenic shock patients from the CULPRIT-SHOCK trial with NSTEMI or LBBBMI were compared with STEMI patients for 30-day and 1-year all-cause mortality. The interaction between ECG presentation and the effect of revascularization strategies on outcomes was evaluated. RESULTS: Of 665 cardiogenic shock patients analyzed, 55.9% demonstrated STEMI, 29.3% demonstrated NSTEMI, and 14.7% demonstrated LBBBMI. Patients differed in mean age (68.0 years in STEMI patients, 71.0 years in NSTEMI patients, and 73.5 years in LBBBMI patients; P = .015), cardiovascular risk factors, and angiographic severity. No difference was found in the 30-day risk of death between NSTEMI and STEMI patients (48.7% vs 43.0%; adjusted OR [aOR], 1.05; 95% CI, 0.66-1.67; P = .85), nor between LBBBMI and STEMI patients (59.2% vs 43.0%; aOR, 1.31; 95% CI, 0.73-2.34; P = .36). Although the univariate risk of death by 1 year was higher in NSTEMI and LBBBMI patients compared with STEMI patients, ECG presentation was not an independent risk factor of mortality after adjustment (NSTEMI vs STEMI: 56.4% vs 46.8%; aOR, 1.21; 95% CI, 0.76-1.92; P = .42; LBBBMI vs STEMI: 69.4% vs 46.8%; aOR, 1.59; 95% CI, 0.89-2.84; P = .12). ECG presentation did not modify the effect of the revascularization strategy on 30-day and 1-year mortality (P = .91 and P = .97 for interaction). INTERPRETATION: In patients with cardiogenic shock, NSTEMI and LBBBMI presentations reflect higher-risk profiles than STEMI presentations, but are not independent risk factors of mortality. ECG presentations did not modify the treatment effect, supporting culprit-lesion-only percutaneous coronary intervention as the preferred strategy across the AMI spectrum.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials.

AIMS: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. METHODS AND RESULTS: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). CONCLUSIONS: GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.

Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS).

BACKGROUND: Adverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes. METHODS: In a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events. DISCUSSION: Despite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR. ETHICS/DISSEMINATION: The study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations. TRIAL REGISTRATION: ClinicalTrials.govNCT03585933. Registered on 02 July 2018.