Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Rate and predictors of blood culture positivity after antibiotic administration: a prospective single-center study.

PURPOSE: Blood culture obtainment prior to antibiotic administration, in patients with suspected infection, is considered the best practice in international guidelines. However, there is little data regarding the effect of a single dose of antibiotics on blood culture sterilization. METHODS: We conducted a prospective study, enrolling consecutive patients with suspected infection, hospitalized in an internal medicine ward between December 2019 and January 2023. Included patients had a positive blood culture prior to antibiotic administration and a set of blood cultures taken within 24 h after a single dose of antibiotics. The rate of patients with pathogen isolation after antibiotic administration was assessed. Logistic regression was performed to examine factors associated with blood culture positivity. RESULTS: A total of 155 patients were recruited for the study of which 131 (50.8% female 77.5 ± 13.4 years) met the inclusion criteria. The overall rate of patients with a positive blood culture after a single dose of antibiotics was 42.0% (55/131 patients). Increasing time between antibiotic administration and post-antibiotic culture was an independent predictor for blood culture sterilization (odds ratio 0.89 [95% confidence interval, 0.83-0.97; p = 0.006] for every 60 min). Blood culture volume was an independent predictor for blood culture positivity in a sensitivity analysis which included 82 patients (OR = 1.26 [95% CI 1.03-1.57] for every 1 ml increase; p = 0.024). CONCLUSION: Blood culture positivity is reduced by antimicrobial therapy but remains high after a single dose of antibiotics. If cultures are not obtained prior to antibiotic administration, they should be obtained as soon as possible afterwards.

Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients.

BACKGROUND: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. METHODS: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h). RESULTS: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03). CONCLUSIONS: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

C-Reactive Protein Velocity and the Risk of New Onset Atrial Fibrillation among ST Elevation Myocardial Infarction Patients.

BACKGROUND: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known. OBJECTIVES: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI. METHODS: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF. RESULTS: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0-3.59, P = 0.04) for patients in the third CRPv tertile. CONCLUSIONS: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.

Prognostic Implication of Tricuspid Regurgitation in ST-segment Elevation Myocardial Infarction Patients.

BACKGROUND: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients. OBJECTIVES: To investigate the possible implication of TR among STEMI patients. METHODS: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded. RESULTS: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06-5.6, P = .036) for patients with moderate to severe TR. CONCLUSIONS: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Prognostic Implication of Tricuspid Regurgitation in ST-segment Elevation Myocardial Infarction Patients.

BACKGROUND: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients. OBJECTIVES: To investigate the possible implication of TR among STEMI patients. METHODS: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded. RESULTS: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06-5.62; P = 0.036) for patients with moderate-severe TR. CONCLUSIONS: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Long-Term Outcomes in ST Elevation Myocardial Infarction Patients Undergoing Coronary Artery Bypass Graft Versus Primary Percutaneous Coronary Intervention.

BACKGROUND: Coronary artery bypass grafting (CABG) for primary reperfusion in patients with ST elevation myocardial infarction (STEMI) has largely been superseded byf primary percutaneous coronary intervention (PCI) and is estimated to be performed in ≤ 5% of STEMI cases. OBJECTIVES: To compare early CABG (within 30 days following admission) and primary PCI outcomes following STEMI. METHODS: We analyzed a retrospective cohort of patients hospitalized with acute STEMI for early reperfusion therapy between January 2008 and June 2016. Short- and long-term outcomes were assessed for patients with STEMI undergoing primary PCI vs. early CABG as reperfusion therapy. RESULTS: The study comprised 1660 STEMI patients, 38 of whom (2.3%) underwent CABG within 30 days of presentation. Unadjusted 30-day mortality was more than twice as high in the CABG group (7.5%) than in the PCI group (3.3%); however, it did not reach statistical significance. Similar results were demonstrated for mortality rates beyond 30 days (22% vs. 14%, P = 0.463). All patients undergoing CABG beyond 72 hours following admission survived past 2 years. Multivariate analysis found no differences between the two groups in long-term mortality risk. propensity score matched long-term mortality comparison (30 days-2 years) yielded a 22% mortality rate in the CABG groups compared with 14% in the PCI group (P < 0.293). CONCLUSIONS: Early CABG was performed in only a minority of STEMI patients. This high-risk patient population demonstrated worse outcomes compared to patients undergoing PCI. Performing surgery beyond 72 hours following admission may be associated with lower risk.

Relation of Subclinical Hypothyroidism to Acute Kidney Injury Among ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Data suggest that subclinical hypothyroidism (SCH) is associated with progression of chronic renal disease; however, no study to date has assessed the possible relation between SCH and acute deterioration of renal function. OBJECTIVES: To investigate the possible relation between SCH and acute kidney injury (AKI) in a large cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary coronary intervention (PCI). METHODS: We evaluated thyroid stimulating hormone (TSH) and free T4 levels of 1591 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit (October 2007-August 2017). The presence of SCH was defined as TSH levels ≥ 5 mU/ml in the presence of normal free T4 levels. Patients were assessed for development of AKI ( 0.3 mg/dl increase in serum creatinine, according to the KDIGO criteria). RESULTS: The presence of SCH was demonstrated in 68/1593 (4.2%) STEMI patients. Patients presenting with SCH had more AKI complications during the course of STEMI (20.6% vs. 9.6 %; P = 0.003) and had significantly higher serum creatinine change throughout hospitalization (0.19 mg/dl vs. 0.08 mg/dl, P = 0.04). No significant difference was present in groups regarding baseline renal function and the amount of contrast volume delivered during coronary angiography. In multivariate logistic regression model, SCH was independently associated with AKI (odds ratio = 2.19, 95% confidence interval 1.05-4.54, P =0.04). CONCLUSIONS: Among STEMI patients treated with PCI, the presence of SCH is common and may serve as a significant marker for AKI.

Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome.

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

Exercise limitation in hypertrophic cardiomyopathy: combined stress echocardiography and cardiopulmonary exercise test.

AIMS: The study aims to investigate exercise-limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. METHODS AND RESULTS: A symptom-limited ramp bicycle exercise test was performed in the semi-supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty-six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex-matched 29 controls. At rest, compared with controls, E/E' ratio (6.26 ± 2.3 vs. 14 ± 2.5, P < 0.001) and systolic pulmonary artery pressures (SPAP) (22.6 ± 3.4 vs. 34 ± 6.2 mmHg, P = 0.023) were increased. Along with the stages of exercise (unloaded; anaerobic threshold; peak), diastolic function worsened (E/e' 8.9 ± 2.6 vs. 13.8 ± 3.6 P = 0.011; 9.4 ± 2.3 vs. 18.6 ± 3.3 P = 0.001; 8.7 ± 1.9 vs. 21.5 ± 4, P < 0.001), SPAP increased (23 ± 2.7 vs. 33 ± 4.4, P = 0.013; 26 ± 3.2 vs. 40 ± 2.9, P < 0.001; 26 ± 3.5 vs. 45 ± 7 mmHg, P < 0.001), and oxygen consumption (6.6 ± 1.7 vs. 6.8 ± 1.6, P = 0.86; 18.1 ± 2.2 vs. 14.6 ± 1.5, P = 0.008; 20.3 ± 3 vs. 15.1 ± 2.1 mL/kg/min, P = 0.01) was reduced. Oxygen pulse was blunted (6.3 ± 1.8 vs. 6.2 ± 1.9, P = 0.79; 10 ± 2.1 vs. 8.8 ± 1.6, P = 0.063; 12.2 ± 2 vs. 8.2 ± 2.3 mL/beat, P = 0.002) due to an insufficient increase in both stroke volume (92.3 ± 17 vs. 77.3 ± 14.5 P = 0.021; 101 ± 19.1 vs. 87.3 ± 15.7 P = 0.06; 96.5 ± 12.2 vs. 83.6 ± 16.1 mL, P = 0.034) and oxygen extraction (0.07 ± 0.03 vs. 0.07 ± 0.02, P = 0.47; 0.13 ± 0.02 vs. 0.10 ± 0.03, P = 0.013; 0.13 ± 0.03 vs. 0.11 ± 0.03, P = 0.03). Diastolic dysfunction, elevated SPAP, and the presence of atrial fibrillation were associated with reduced exercise capacity. CONCLUSIONS: Both central and peripheral cardiovascular limitations are involved in exercise intolerance in HCM. Diastolic dysfunction seems to be the main driver for this limitation.

Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.

BACKGROUND: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited. AIMS: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function. METHODS: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI). RESULTS: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition). CONCLUSIONS: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Risk stratification according to diastolic function indices in heart failure patients with mildly reduced or reduced ejection fraction.

Aims: The aim of the study is to evaluate the risk of all-cause mortality or heart failure hospitalizations in ambulatory patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF or HFmrEF) according to diastolic function indices. Diastolic dysfunction in HF is both common and associated with poor prognosis. However, specific cut-off values of diastolic function parameters for prognostication of hard outcomes in HF have not been conclusively established. Methods and results: Analysis of full echocardiographic examination of consecutive ambulatory HFrEF and HFmrEF patients seen at a single tertiary hospital between 2010 and 2021 was retrospectively done. Data on all-cause mortality or heart failure hospitalizations were obtained from the electronic medical records and national mortality registry. Patients with > moderate left heart valvular dysfunction were excluded from the study. The final cohort included 4717 patients (75% males, median age 70 years interquartile range 61.3-78.4). After adjusting for clinical or echocardiographic variables, increased rates of mortality or HF hospitalizations were found when E/e'>10, left atrial volume index (LAVI) > 40 mL/m2, E/A ratio < 0.6, deceleration time (DT) < 180 ms, peak E-wave velocity > 0.78 m/s, and sPAP > 26 mmHg. However, no significant difference in outcomes between near-normal and normal values of E/e' (< 8 compared with 8-10) or LAVI (≤34 mL/m2 compared with LAVI 34-40 mL/m2) was found. Conclusion: In patients with HFmrEF and HFrEF, slightly abnormal diastolic indices were found to be associated with worse outcomes. Summary: We have demonstrated that in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF or HFmrEF), near-normal diastolic indices are associated with worse outcomes with the following cut-off values: max E-wave velocity > 0.78 m/s, E/e' ratio > 10, a LAVi > 40 mL/m2, DT > 180, E/A between 0.6 and 1.4, and a sPAP > 26 mmHg. Further research is needed to establish these suggested cut-off values.

Risk factors, clinical characteristics and prognostic value of acute kidney injury in COVID-19 compared with influenza virus and respiratory syncytial virus.

BACKGROUND: Acute Kidney Injury (AKI) complicates a substantial part of patients with COVID-19. Direct viral penetration of renal cells through the Angiotensin Converting Enzyme 2 receptor, and indirect damage by the aberrant inflammatory response characteristic of COVID-19 are likely mechanisms. Nevertheless, other common respiratory viruses such as Influenza and Respiratory Syncytial Virus (RSV) are also associated with AKI. METHODS: We retrospectively compared the incidence, risk factors and outcomes of AKI among patients who were admitted to a tertiary hospital because of infection with COVID-19, influenza (A + B) or RSV. RESULTS: We collected data of 2593 patients hospitalized with COVID-19, 2041 patients with influenza and 429 with RSV. Patients affected by RSV were older, had more comorbidities and presented with higher rates of AKI at admission and within 7 days (11.7% vs. 13.3% vs. 18% for COVID-19, influenza and RSV, respectively p = 0.001). Nevertheless, patients hospitalized with COVID-19 had higher mortality (18% with COVID-19 vs. 8.6% and 13.5% for influenza and RSV, respectively P < 0.001) and higher need of mechanical ventilation (12.4% vs. 6.5% vs.8.2% for COVID-19, influenza and RSV, respectively, P = 0.002). High ferritin levels and low oxygen saturation were independent risk factors for severe AKI only in the COVID-19 group. AKI in the first 48 h of admission and in the first 7 days of hospitalization were strong independent risk factors for adverse outcome in all groups. CONCLUSION: Despite many reports of direct kidney injury by SARS-COV-2, AKI was less in patients with COVID-19 compared to influenza and RSV patients. AKI was a prognostic marker for adverse outcome across all viruses.

First-Phase Ejection Fraction and Long-Term Survival in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Early recognition of deteriorating left ventricular function plays a key prognostic role in patients with aortic stenosis (AS). First-phase ejection fraction (EF1), the ejection fraction (EF) up to time of maximal contraction, has been suggested for detection of early left ventricular dysfunction in patients with AS with preserved EF. This work aims to evaluate the predictive value of EF1 for assessment of long-term survival in patients with symptomatic severe AS and preserved EF who undergo transcatheter aortic valve implantation (TAVI). We included 102 consecutive patients (median age 84 years [interquartile range 80 to 86 years]) who underwent TAVI between 2009 and 2011. Patients were retrospectively stratified into tertiles by EF1. Device success and procedural complications were defined according to the Valve Academic Research Consortium-3 criteria. Mortality data were retrieved from a computerized interface of the Israeli Ministry of Health. Baseline characteristics, co-morbidities, clinical presentation, and echocardiographic findings were similar among groups. The groups did not differ significantly regarding device success and in-hospital complications. During a potential follow-up period of >10 years, 88 patients died. Kaplan-Meier analysis (log-rank p = 0.017) followed by multivariable Cox regression analysis showed that EF1 predicted long-term mortality independently, either as continuous variable (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07, p = 0.012) or for each decrease in tertile group (hazard ratio 1.40, 95% confidence interval 1.05 to 1.86, p = 0.023). In conclusion, low EF1 is associated with a significant decrease in adjusted hazard for long-term survival in patients with preserved EF who undergo TAVI. Low EF1 might delineate a population at great risk who would benefit from prompt intervention.

High neutrophil-to-lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline.

BACKGROUND: Cardiotoxicity, defined mainly as left ventricle (LV) dysfunction, is a significant side effect of anthracyclines (ANT) therapy. The need for an early simple marker to identify patients at risk is crucial. A high neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in cancer patients; however, its role as a predictor for cardiotoxicity development is unknown. OBJECTIVE: Evaluating whether elevated NLR, during ANT exposure, plays a predictive role in the development of cardiotoxicity as defined by LV global longitudinal strain (LV GLS) relative reduction (≥10%). METHODS AND RESULTS: Data were prospectively collected as part of the Israel Cardio-Oncology Registry. A total of 74 female patients with breast cancer, scheduled for ANT therapy were included. NLR levels were assessed at baseline (T1) and during ANT therapy (T2). All patients underwent serial echocardiography at baseline (T1) and after the completion of ANT therapy (T3). NLR ≥ 2.58 at T2 was found to be the optimal predictive cutoff for LV GLS deterioration. A relative LV GLS reduction ≥10% was significantly more common among patients with high NLR (50% vs. 20%, p = .009). NLR ≥ 2.58 at T2 increases the risk for LV GLS reduction by fourfold (odds ratio [OR]: 4.63, 95% confidence interval [CI]: 1.29-16.5, p = .02), with each increase of 1-point NLR adding an additional 15% risk (OR: 1.15, 95% CI: 1.01-1.32, p = .046). CONCLUSIONS: Our study provides novel data that high NLR levels, during ANT exposure, have an independent association with the development of LV dysfunction. Routine surveillance of NLR may be an effective means of risk-stratifying.

The Mechanism of Effort Intolerance in Patients with Peripheral Arterial Disease: A Combined Stress Echocardiography and Cardiopulmonary Exercise Test.

AIM: We used a combined stress echocardiography and cardiopulmonary exercise test (CPET) to explore effort intolerance in peripheral arterial disease (PAD) patients. METHODS: Twenty-three patients who had both PAD and coronary artery disease (CAD) were compared with twenty-four sex- and age-matched CAD patients and fifteen normal controls using a symptom-limited ramp bicycle CPET on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. RESULTS: Along the stages of exercise (unloaded; anaerobic threshold; peak), in PAD + CAD patients compared with CAD or controls, diastolic function worsened (p = 0.051 and p = 0.013, respectively), and oxygen consumption (p < 0.001 and p < 0.001, respectively) and oxygen pulse (p = 0.0024 and p = 0.0027, respectively) were reduced. Notably, oxygen pulse was blunted due to an insufficient increase in both stroke volume (p = 0.025 and p = 0.028, respectively) and peripheral oxygen extraction (p = 0.031 and p = 0.038, respectively). Chronotropic incompetence was more prevalent in PAD patients and persisted after correction for beta-blocker use (62% vs. 42% and 11%, respectively). CONCLUSIONS: In PAD patients, exercise limitation is associated with diastolic dysfunction, chronotropic incompetence and peripheral factors.

Vascular Complications in Transcatheter Aortic Valve Replacement With Plug-Based vs Suture-Based Closure Devices.

BACKGROUND: There are conflicting data regarding the efficacy and safety of suture vs plug-based vascular closure devices (VCDs) for large-bore catheter management in patients undergoing transcatheter aortic valve replacement (TAVR). We compared the rates of vascular complications (VCs) associated with 2 commonly used VCDs in a large cohort of patients undergoing TAVR. METHODS: We conducted a single-centre, all-comer, prospective registry study, enrolling patients undergoing TAVR for symptomatic severe aortic stenosis (AS) between the years 2009 and 2022. Clinical outcomes were compared between patients undergoing closure of the femoral access point using the MANTA VCD (M-VCD) (Teleflex, Wayne, PA) vs the ProGlide VCD (P-VCD) (Abbott Vascular, Abbott Park, IL). The main outcome measures were researcher adjudicated events of VARC-2 defined major and minor VCs. RESULTS: Overall, 2368 patients were enrolled in the registry; 1315 (51.0% male, 81.0 ± 7.0 years) patients were included in the current analysis. P-VCD was used in 813 patients, whereas M-VCD was used in 502 patients. In-hospital VCs were more frequent in the M-VCD vs the P-VCD group (17.3% vs 9.8%; P < 0.001). This outcome was mainly driven by elevated rates of minor VCs in the M-VCD group, whereas no significant difference was observed for major VCs (15.1% vs 8.4%; P < 0.001 and 2.2% vs 1.5%; P = 0.33, respectively). CONCLUSIONS: In patients undergoing TAVR for severe AS, M-VCD was associated with higher rates of VCs. This outcome was mainly driven by minor VCs. The rate of major VCs was low in both groups.

Cardiologic Manifestations in Omicron-Type Versus Wild-Type COVID-19: A Systematic Echocardiographic Study.

Background Information about the cardiac manifestations of the Omicron variant of COVID-19 is limited. We performed a systematic prospective echocardiographic evaluation of consecutive patients hospitalized with the Omicron variant of COVID-19 infection and compared them with similarly recruited patients were propensity matched with the wild-type variant. Methods and Results A total of 162 consecutive patients hospitalized with Omicron COVID-19 underwent complete echocardiographic evaluation within 24 hours of admission and were compared with propensity-matched patients with the wild-type variant (148 pairs). Echocardiography included left ventricular (LV) systolic and diastolic, right ventricular (RV), strain, and hemodynamic assessment. Echocardiographic parameters during acute infection were compared with historic exams in 62 patients with the Omicron variant and 19 patients with the wild-type variant who had a previous exam within 1 year. Of the patients, 85 (53%) had a normal echocardiogram. The most common cardiac pathology was RV dilatation and dysfunction (33%), followed by elevated LV filling pressure (E/e' ≥14, 29%) and LV systolic dysfunction (ejection fraction <50%, 10%). Compared with the matched wild-type cohort, patients with Omicron had smaller RV end-systolic areas (9.3±4 versus 12.3±4 cm2; P=0.0003), improved RV function (RV fractional-area change, 53.2%±10% versus 39.7%±13% [P<0.0001]; RV S', 12.0±3 versus 10.7±3 cm/s [P=0.001]), and higher stroke volume index (35.6 versus 32.5 mL/m2; P=0.004), all possibly related to lower mean pulmonary pressure (34.6±12 versus 41.1±14 mm Hg; P=0.0001) and the pulmonary vascular resistance index (P=0.0003). LV systolic or diastolic parameters were mostly similar to the wild-type variant-matched cohort apart from larger LV size. However, in patients who had a previous echocardiographic exam, these LV abnormalities were recorded before acute Omicron infection, but not in the wild-type cohort. Numerous echocardiographic parameters were associated with higher in-hospital mortality (LV ejection fraction, stroke volume index, E/e', RV S'). Conclusions In patients with Omicron, RV function is impaired to a lower extent compared with the wild-type variant, possibly related to the attenuated pulmonary parenchymal and/or vascular disease. LV systolic and diastolic abnormalities are as common as in the wild-type variant but were usually recorded before acute infection and probably reflect background cardiac morbidity. Numerous LV and RV abnormalities are associated with adverse outcome in patients with Omicron.

Acute Kidney Injury Recovery Patterns in ST-Segment Elevation Myocardial Infarction Patients.

Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p < 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p < 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933−4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker.