Yacov Shacham

Background: Reduced estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI) are common in patients with ST-segment elevation myocardial infarction (STEMI) and adversely influence prognosis. This retrospective cohort study evaluated the association between admission eGFR and one-year mortality following STEMI, accounting for admission AKI and cardiovascular risk factors. Methods: Consecutive adults (n = 2903) admitted with STEMI undergoing primary percutaneous coronary intervention (PCI) at a tertiary center were analyzed, selected from 2949 initially screened patients after excluding those treated conservatively or with thrombolysis (n = 14), those with a final discharge diagnosis other than STEMI (n = 21), and early deaths within 24 h of presentation (n = 11). Admission eGFR was calculated using the 2021 CKD-EPI creatinine equation and categorized into quintiles. The primary outcome was all-cause one-year mortality, assessed using multivariable logistic regression and secondary Kaplan–Meier survival analysis. Results: Both one-year and 30-day crude mortality decreased markedly across increasing eGFR quintiles (p < 0.001), a pattern that was maintained among patients presenting without admission AKI (30-day mortality: Q5 4.4% vs. Q1 0.0%, p < 0.001). In crude analysis, 30-day mortality was 9.1% in the lowest eGFR quintile overall. Multivariable logistic regression identified advancing age (OR 1.05 per year, p < 0.001) and admission AKI (OR 7.07, p < 0.001) as the dominant independent predictors of one-year mortality, whereas individual eGFR quintiles were attenuated after adjustment (global Wald p = 0.047). Conclusions: Lower admission eGFR is significantly associated with one-year mortality after STEMI in crude and unadjusted analyses, but its predictive contribution is substantially attenuated following multivariable adjustment for advancing age and admission AKI, which serve as the dominant prognostic determinants. Rather than acting as a strong isolated independent predictor, admission renal function primarily serves as an indicator of baseline cardiorenal reserve and baseline patient vulnerability.

Mortality from acute ST elevation myocardial infarction (STEMI) was significantly reduced with the introduction of percutaneous catheterization intervention (PCI) but remains high in patients who develop acute kidney injury (AKI). Previous studies found overweight to be protective from mortality in patients suffering from STEMI and AKI separately but not as they occur concurrently. This study aimed to establish the relationship between AKI and mortality in STEMI patients after PCI and whether body mass index (BMI) has a protective impact. Between January 2008 and June 2016, two thousand one hundred and forty-one patients with STEMI underwent PCI and were admitted to the Tel Aviv Medical Center Cardiac Intensive Care Unit. Their demographic, laboratory, and clinical data were collected and analyzed. We compared all-cause mortality in patients who developed AKI after PCI for STEMI and those who did not. In total, 178 patients (10%) developed AKI and had higher mortality (p < 0.001). Logistic regression analysis was performed to determine the relationship between AKI, BMI, and mortality. AKI was significantly associated with both 30-day and overall mortality, while BMI had a significant protective effect. Survival analysis found a significant difference in 30-day and overall survival between patients with and without AKI with a significant protective effect of BMI on survival at 30 days. AKI presents a major risk for mortality and poor survival after PCI for STEMI, yet a beneficial effect of increased BMI modifies it.

Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment for patients with severe AS. Since the TAVR population and patients’ outcomes have dramatically changed over the last decade, updated data regarding contemporary practice and trends are pertinent to clinical use. We performed a retrospective observational analysis of consecutive patient who underwent TAVR for symptomatic severe AS between the years 2009 and 2021 in a single high-volume center. Patients were divided into four equal time groups based on the procedure date (2009–2012, 2013–2015, 2016–2018 and 2019–2021). A total of 1988 patients were included in this study and divided into four groups, with 321, 482, 565 and 620 patients in groups 1–4, respectively. Significant trends were seen in baseline characteristics of a few parameters, including lower age, lower procedural risk and reduced rates of comorbidity (p for trend < 0.0001 for all factors mentioned above). A shift was seen in the procedural technique with lower balloon pre-dilatation and higher device success rates (p for trend < 0.0001). The post-procedural period changed over the years with fewer pacemaker placements (p < 0.0001) and reduced rates of AKI and post-procedural bleed (p value 0.02 and p < 0.0001). Finally, patient follow up revealed reduced mortality rates at 30 days (p < 0.0001) and 1 year (p = 0.013). Multivariate regression revealed that a late implantation date was an independent protector from mortality (HR 0.84, p = 0.002). In conclusion, our study demonstrated that TAVR has become a safer practice over the years with reduced rates of morbidity and mortality.

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p < 0.01. Furthermore, patients with both high CRP and high troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p < 0.01. These patients also had the highest all-cause mortality rates after a median follow-up of 4.5 years compared to the rest of the cohort; 42.9% vs. 12.7%, p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents.

Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients treated with primary coronary intervention (PCI). Methods: We performed a prospective, observational, open-label trial. High NGAL was defined as values within the third tertile (>66 percentile). Results: A total of 267 patients were included (mean age 66 ± 14 years, 81% males). Short-term adverse outcomes were consistently increased in the high NGAL group with more acute kidney injury, lower mean left ventricular ejection fraction, higher 30-day mortality, and higher incidence for the composite outcome of major adverse cardiac events (MACE). In a multivariate logistic regression model, high NGAL emerged as a strong and independent predictor for MACE (OR 2.07, 95% CI 1.15–3.73, p = 0.014). Conclusions: Among STEMI patients undergoing primary PCI, elevated NGAL levels are associated with adverse renal and cardiovascular outcomes, independent of traditional inflammatory markers. Further studies are needed to assess the potentially unique role of NGAL in cardio–renal interactions.

Background: Among patients with rhabdomyolysis, the leakage of intracellular skeletal muscle content such as creatine phosphokinase (CPK) into the bloodstream has been associated with an increased risk of acute kidney injury (AKI). We evaluated the possible relationship between serum CPK levels and AKI occurrence among patients with myocyte injury secondary to ST-elevation myocardial infarction (STEMI). Methods: We retrospectively included 2794 patients with STEMI. Patients were stratified according to peak serum CPK levels into mild (5000 U/L, n = 80) categories. The occurrence of AKI was defined by the KDIGO criteria as an increase in serum creatinine (sCR) ≥0.3 mg/dL within 48 h following PCI. The predictive value of CPK for the risk of AKI occurrence was assessed using multivariate logistic regression models. Results: The overall occurrence of AKI was 10.4%. Incidence of AKI showed a gradual increase between patients with mild, moderate, and severe serum CPK level elevations (7.8% vs. 11% vs. 26% respectively; p < 0.001). In multivariate logistic regression models, both moderate or higher (OR 1.6, 95% CI 1.1–2.2; p = 0.01) and severe (OR 2.8 95% CI 1.4–5.6; p = 0.004) serum CPK level elevations were independently associated with AKI. Conclusions: Among STEMI patients, elevated CPK levels were associated with AKI. This association is presumably independent; however, it remains unclear whether it is due to direct toxic (myoglobin-related) or hemodynamic effects (poor left ventricular function). Further studies are required to reveal the underlying mechanism.

C-reactive protein velocity (CRPv), defined as the change in wide-range CRP concentration divided by time, is an inflammatory biomarker associated with increased morbidity and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). However, data regarding CRPv association with echocardiographic parameters assessing left ventricular systolic and diastolic function is lacking. Echocardiographic parameters and CRPv values were analyzed using a cohort of 1059 patients admitted with STEMI and treated with primary PCI. Patients were stratified into tertiles according to their CRPv. A receiver operating characteristic (ROC) curve was used to evaluate CRPv optimal cut-off values for the prediction of severe systolic and diastolic dysfunction. Patients with high CRPv tertiles had lower left ventricular ejection fraction (LVEF) (49% vs. 46% vs. 41%, respectively; p < 0.001). CRPv was found to independently predict LVEF ≤ 35% (HR 1.3 CI 95% 1.21–1.4; p < 0.001) and grade III diastolic dysfunction (HR 1.16 CI 95% 11.02–1.31; p = 0.02). CRPv exhibited a better diagnostic profile for severe systolic dysfunction as compared to CRP (area under the curve 0.734 ± 0.02 vs. 0.608 ± 0.02). In conclusion, For STEMI patients treated with primary PCI, CRPv is a marker of both systolic and diastolic dysfunction. Further larger studies are needed to support this finding.

Background: Hepatic injury secondary to congestive heart failure is well described, however, only limited data exist about the possible impact of acute cardiac dysfunction on the liver. We aimed to explore the possible cardio-hepatic interaction in patients with myocardial infarction. Material and methods: A single-center retrospective cohort study of 1339 ST elevation myocardial infarction (STEMI) patients who underwent primary coronary intervention between June 2012 to June 2019. Echocardiographic examinations were performed to assess left ventricular ejection fraction (LVEF) and central venous pressure (CVP). Patients were stratified into four groups by their LVEF and CVP levels: LVEF ≥ 45%, and CVP ≤ 10 mm/Hg (n = 853), LVEF < 45% with CVP ≤ 10 mm/Hg (n = 364), EF ≥ 45%, with CVP > 10 mm/Hg (n = 61), and LVEF < 45% with CVP > 10 mm/Hg (n = 61). Patients were evaluated for baseline and peak liver enzymes including alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin. Results: Greater severity of cardiac dysfunction was associated with worse elevation of liver enzymes. We found a graded increase in mean levels of maximal ALT, first and maximal ALP, and first and maximal GGT values. Using propensity score matching to estimate the impact of cardiac dysfunction on liver injury, we chose patients with the worst cardiac function parameters: (LVEF < 45% and CVP >10 mm/Hg; n = 61) and compared them to matched patients with better cardiac function (n = 45). We found a significantly higher level of maximal ALT, first and maximal ALP, and GGT values in the group with the worst cardiac function parameters (p < 0.05). Conclusions: Among patients with STEMI, the combination of decreased LVEF and venous congestion was associated with liver enzymes elevation suggesting a possible cardio-hepatic syndrome.

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.

Background. High-grade AV block (HGAVB) is a life-threatening condition. Acute kidney injury (AKI) which is usually caused by renal hypo-perfusion is associated with adverse outcomes. We aimed to investigate the association between AKI and HGAVB. Methods. This is a retrospective cohort comparing the incidence of AKI among patients with HGAVB requiring pacemaker implantation compared with propensity score matched controls. Primary outcome was the incidence of AKI at admission. Secondary outcomes were change in creatinine levels, AKI during stay, recovery from AKI, mortality and major adverse kidney events (MAKE). Results. In total, 80 HGAVB patients were compared to 400 controls. HGAVB patients had a higher proportion of admission AKI compared to controls (36.2% versus 21.1%, RR = 1.71 [1.21–2.41], p = 0.004). Creatinine changes from baseline to admission and to maximum during hospitalization, were also higher in HGAVB (p = 0.042 and p = 0.033). Recovery from AKI was more frequent among HGAVB patients (55.2% vs. 25.9%, RR = 2.13 [1.31–3.47], p = 0.004) with hospitalization time, MAKE and crude mortality similar (p > 0.158). Conclusions. AKI occurs in about one third of patients admitted with HGAVB, more frequent compared to controls. Patients with AKI accompanying HGAVB were likelier to recover from AKI. Further studies to explore this relationship could aid in clinical decision making for HGAVB patients.