Calcium score of the entire thoracic aorta is an independent predictor of all-cause mortality in patients referred to chest computed tomography.

BACKGROUND: Thoracic arterial calcifications (TAC) are not routinely reported or quantified in chest CT scans. We aimed to evaluate the association between TAC of the entire thoracic aorta and all-cause mortality (ACM) in patients referred to standard chest CT. METHODS: A retrospective analysis of consecutive standard chest CT scans (non-gated, non-contrast) for the quantification of TAC, CAC and aortic valve calcification. TAC was divided into 4 sample-derived categories (TAC 1 = 0, TAC 2 = 1-65, TAC 3 = 66-439 and TAC 4 ≥ 440). Data regarding ACM was retrieved from the health care provider database. Multivariate Cox proportional regression models were used to assess associations between the TAC categories and ACM. RESULTS: The study cohort included 415 patients (mean age 67 years, 52% male); 107 ACM events were recorded during a median follow-up of 9 years (inter-quartile range: 7.4-10.4). The rate of ACM was 13%, 25%, 32%, 41% according to TAC category (p < 0.001). The highest TAC category (≥ 440) was a strong and independent predictor of ACM [HR = 1.69 (1.13-2.52; 0.01)] in multivariate analysis. Other independent predictors of ACM included age [HR = 1.07 (1.04-1.10; p < 0.001)], male sex [HR = 2.27 (1.49-3.46; 0.001)] and malignancy [HR = 2.21 (1.49-3.23; < 0.001)]. CONCLUSIONS: Severe TAC (≥ 440) was found to be an independent predictor of ACM. Thus, we suggest that documenting and quantifying TAC should be routinely incorporated into standard chest CT reports.

Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Significance of Anteroseptal Late Gadolinium Enhancement Among Patients With Acute Myocarditis.

Anteroseptal location of late gadolinium enhancement (LGE) in patients with acute myocarditis (AM) detected by cardiovascular magnetic resonance may indicate an independent marker of unfavorable outcomes according to recent data. We aimed to evaluate the clinical characteristics, management, and inhospital outcomes in patients with AM with positive LGE based on its presence in the anteroseptal location. We analyzed data from 262 consecutive patients hospitalized with a diagnosis of AM with positive LGE within 5 days of hospitalization (n = 425). Patients were divided into 2 groups: those with anteroseptal LGE (n = 25, 9.5%) and those with non-anteroseptal LGE (n = 237, 90.5%). Except for age that was higher in patients with anteroseptal LGE, the demographic and clinical characteristics did not differ significantly between both groups including past medical history, clinical presentation, electrocardiogram parameters, and lab values. Moreover, patients with anteroseptal LGE were more likely to present with reduced left ventricular ejection fraction and to receive congestive heart failure treatments. Although univariate analysis showed that patients with anteroseptal LGE were more likely to have inhospital major adverse cardiac events (28% vs 9%, p = 0.003), there was no difference inhospital outcomes on multivariable analysis between both groups (hazard ratio, 1.17 [95% confidence interval, 0.32 to 4.22], p = 0.81). A higher left ventricular ejection fraction in either echocardiography or cardiovascular magnetic resonance corresponded to better inhospital outcomes regardless of the presence or absence of anteroseptal LGE. In conclusion, the presence of anteroseptal LGE did not confer additional prognostic value for inhospital outcomes.

Clinical predictors of left ventricular thrombus after myocardial infarction as detected by magnetic resonance imaging.

Background: The diagnosis of a left ventricular (LV) thrombus in patients with ST-segment elevation myocardial infarction (STEMI) remains challenging. The aim of the current study is to characterize clinical predictors for LV thrombus formation, as detected by cardiac magnetic resonance imaging (CMRI). Methods: We retrospectively evaluated 337 consecutive STEMI patients. All patients underwent transthoracic echocardiography (TTE) and CMRI during their index hospitalization. We developed a novel risk stratification model (ThrombScore) to identify patients at risk of developing an LV thrombus. Results: CMRI revealed the presence of LV thrombus in 34 patients (10%), of whom 33 (97%) had experienced an anterior wall myocardial infarction (MI), and the majority (77%) had at least mildly reduced left ventricular ejection fraction (LVEF < 45%). The sensitivity for thrombus formation of the first and second TTE was 5.9% and 59%, respectively. Multivariate logistic regression model revealed that elevated C-reactive protein levels, lack of ST-segment elevation (STe) resolution, elevated creatine phosphokinase levels, and STe in anterior ECG leads are robust independent predictors for developing an LV thrombus. These variables were incorporated to construct the ThrombScore: a simple six-point risk model. The odds ratio for developing thrombus per one-point increase in the score was 3.2 (95% CI 2.1-5.01; p < 0.001). The discrimination analysis of the model revealed a c-statistic of 0.86 for thrombus development. The model identified three distinct categories (I, II, and III) with corresponding thrombus incidences of 0%, 1.6%, and 27.6%, respectively. Conclusion: ThrombScore is a simple and practical clinical model for risk stratification of thrombus formation in patients with STEMI.

Early Invasive Strategy and Outcome of Non-ST-Segment Elevation Myocardial Infarction Patients With Chronic Kidney Disease.

BACKGROUND: Current guidelines suggest that an early invasive strategy should be considered for the treatment of non-ST-segment elevation myocardial infarction (NSTEMI). Although chronic kidney disease (CKD) is common among NSTEMI patients, these patients are under-represented in clinical trials, and data regarding their management are limited. OBJECTIVES: The authors sought to evaluate the association between early invasive strategy and long-term survival among patients with NSTEMI and CKD. METHODS: This was a retrospective analysis of 7,107 consecutive NSTEMI patients between 2008 and 2021. Patients were dichotomized into early (≤24 hours) and delayed invasive groups and stratified by kidney function. Inverse probability treatment weighting was used to adjust for differences in baseline characteristics. The primary outcome was all-cause mortality. RESULTS: The final study population comprised 3,529 invasively treated patients with a median age of 66 years (IQR: 58-74 years), 1,837 (52%) of whom were treated early. There were 483 (14%) patients with at least moderate CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2). During a median follow-up of 4 years (IQR: 2-6 years), 527 (15%) patients died. After inverse probability treatment weighting, an early invasive strategy was associated with a significant 30% lower mortality compared with a delayed strategy (HR: 0.7; 95% CI: 0.56-0.85). The association between early invasive strategy and mortality was modified by eGFR (Pinteraction < 0.001) and declined with lower renal function, with no difference in mortality among patients with eGFR <45 mL/min/1.73 m2 (HR: 0.89; 95% CI: 0.64-1.24). CONCLUSIONS: Among NSTEMI patients, the association of early invasive strategy with long-term survival is modified by CKD and was not observed in patients with eGFR <45 mL/min/1.73 m2.

Management and outcome of patients with non-ST elevation myocardial infarction and intercurrent non-coronary precipitating events.

AIMS: To evaluate the effect of an intercurrent non-coronary illness on the management and outcome of patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: Consecutive hospitalized patients with a primary diagnosis of NSTEMI between August 2008 and December 2019 at Sheba Medical Center. All patients' records were reviewed for the presence of a non-coronary precipitating event (NCPE): a major intercurrent acute non-coronary illness or condition, either cardiac or non-cardiac. The primary outcome was all-cause mortality. Cox regression with interaction analysis was applied. Final study population comprised 6491 patients, of whom 2621 (40%) had NCPEs. Patients with NCPEs were older (77 vs. 69 years) and more likely to have comorbidities. The most prevalent event was infection (35%, n = 922). During a median follow-up of 30 months, 2529 patients died. Patients with NCPEs were 43% more likely to die during follow-up in a multivariable model (95% CI: 1.31-1.55). Invasive strategy was associated with a 55% lower mortality among patients without NCPE and only 44% among patients with NCPE (P for interaction < 0.001). Dual antiplatelet therapy (DAPT) was associated with a 20% lower mortality in patients without NCEP and a non-significant mortality difference among patients with NCPE (P for interaction = 0.014). Sub-analysis by the specific NCPE showed the highest mortality risk among patients with infectious precipitant. The lower mortality associated with invasive strategy was not observed in this subgroup. CONCLUSION: Among NSTEMI patients, the presence of an NCPE is associated with poor survival and modifies the effect of management strategies.

Occluded vein as a predictor for complications in non-infectious transvenous lead extraction.

Background: The use of cardiovascular implantable electronic device (CIED) is steadily increasing, and complications include venous occlusion and fractured leads. Transvenous lead extraction (TLE) can facilitate the re-implantation of new leads. Aims: This study aims to explore predictors and complications of non-infectious TLE. Methods: This study involves a retrospective analysis and comparison of characteristics, complications, and outcomes of patients with and without occluded veins (OVs) undergoing TLE at our center. Results: In total, eighty-eight patients underwent TLE for non-infectious reasons. Indications for TLE were lead malfunction (62; 70.5%) and need for CIED upgrade (22; 25%). Fourteen patients referred due to lead malfunction had an OV observed during venography. The OV group (36 patients) were significantly older (65.7 ± 14.1 vs. 53.8 ± 15.9, p = 0.001) and had more comorbidities. Ejection fraction (EF) was significantly lower for the OV group (27.5 vs. 57.5%, p = 0.001) and had a longer lead dwelling time (3,226 ± 2,324 vs. 2,191 ± 1,355 days, p = 0.012). Major complications were exclusive for the OV group (5.5% vs. none, p = 0.17), and most minor complications occurred in the OV group as well (33.3 vs. 4.1%, p < 0.001). Laser sheath and mechanical tools for TLE were frequently used for OV as compared to the non-occluded group (94.4 vs. 73.5%, respectively, p = 0.012). Procedure success was higher in the non-occluded group compared to the OV group (98 vs. 83.3%, respectively, p = 0.047). Despite these results, periprocedural mortality was similar between groups. Conclusion: Among the TLE for non-infectious reasons, vein occlusion appears as a major predictor of complex TLE tool use, complications, and procedural success. Venography should be considered prior to non-infectious TLE to identify high-risk patients.

Pericardial Involvement in ST-Segment Elevation Myocardial Infarction as Detected by Cardiac MRI.

Background: Post myocardial infarction pericarditis is considered relatively rare in the current reperfusion era. The true incidence of pericardial involvement may be underestimated since the diagnosis is usually based on clinical and echocardiographic parameters. Objectives: This study aims to document the incidence, extent, and prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction (PISTEMI) using cardiac MRI (CMR). Methods: One hundred and eighty-seven consecutive ST-segment elevation myocardial infarction patients underwent CMR on day 5 ± 1 following admission, including steady-state free precession (SSFP) and late Gadolinium enhancement (LGE) sequences. Late Gadolinium enhancement and microvascular obstruction (MVO) were quantified as a percentage of left ventricular (LV) mass. Late Gadolinium enhancement was graded for transmurality according to the 17 AHA left ventricle (LV) segment model (LGE score). Late pericardial enhancement (LPE), the CMR evidence of pericardial involvement, was defined as enhanced pericardium in the LGE series and was retrospectively recorded as present or absent according to the 17 AHA segments. Late pericardial enhancement was evaluated adjacent to the LV, the right ventricle, and both atria. Clinical, laboratory, angiographic, and echocardiographic data were collected. Clinical follow-up for major adverse cardiac events (MACE) was documented and correlated with CMR indices, including LGE, MVO, and LPE. Results: Late pericardial enhancement (LPE+) was documented in 77.5% of the study cohort. A strong association was found between LPE and the degree and extent of myocardial injury (LGE, MVO). Both LGE and MVO were significantly correlated with increased MACE on follow-up. On the contrary, LPE presence, either adjacent to the LV or the other cardiac chambers, was associated with a lower MACE rate in a median of 3 years of follow-up HR 0.39, 95% CI (0.21-0.7), p = 0.002, and HR 0.48, 95% CI (0.26-0.9), p = 0.02, respectively. Conclusions: Prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction was documented by CMR in 77.5% of our STEMI cohort. Late pericardial enhancement presence correlated significantly with the extent and severity of the myocardial damage. Unexpectedly, it was associated with a considerably lower MACE rate in the follow-up period.

Post-ST-Segment-Elevation Myocardial Infarction Platelet Reactivity Is Associated With the Extent of Microvascular Obstruction and Infarct Size as Determined by Cardiac Magnetic Resonance Imaging.

Background Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST-segment-elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO. Methods and Results We prospectively evaluated 105 patients in 2 distinct periods (2012-2013 and 2016-2018) who presented with first ST-segment-elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO (P<0.01 for each). Adjusted multivariable logistic regression model revealed that suboptimal response to DAPT is significantly associated with both greater late gadolinium enhancement (P<0.01) and MVO extent (odds ratio, 3.7 [95% CI, 1.3-10.5]; P=0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1-year follow-up (37% versus 11%; P<0.01). Conclusions In patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.

Increased Rate of New-onset Left Bundle Branch Block in Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation (From a National Registry).

There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

Transcatheter Aortic Valve Implantation During the COVID-19 Pandemic.

Transcatheter aortic valve implantation (TAVI) outcomes during the coronavirus disease 2019 (COVID-19) pandemic have not been fully evaluated and some structural programs in the world have been suspended during this period. We sought to evaluate and compare clinical outcomes in patients undergoing TAVI in pandemic versus nonpandemic era. In a single center, we compared 198 TAVI patients performed during 2019 to 59 patients performed during the COVID-19 pandemic period (March 1st to June 30th, 2020). Primary outcome was procedural success according to VARC criteria and 30-day mortality rates. VARC-defined procedural success was high in both groups (93.3% vs 96.6%; p = 0.53). There were no differences in any vascular complications (26% vs 19%; p = 0.3), permanent pacemaker implantation (11.8% vs 15.3%; p = 0.63), and length of hospital stay (5.2 vs 4.2 days; p = 0.29). Thirty-day mortality was similar (3% vs 3.4%; p = 1.0). We had no documented COVID-19 disease in our patients during follow up. In conclusion, TAVI procedures can be performed effectively and safely during the COVID-9 pandemic, using a minimalist approach, early discharge, and by maintaining proper use of personal protective equipment.

Publisher Correction: Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Norton score and clinical outcomes following acute decompensated heart failure hospitalization.

BACKGROUND: Norton scoring system is used to assess frailty of hospitalized patients with various medical conditions. We aimed to evaluate whether admission Norton scoring system predicts adverse outcomes among heart failure patients. METHODS: The study population comprised 4388 acute heart failure patients between the years 2008 and 2017. Patients were allocated to 3 groups according to their admission Norton score [(≤15-low, 16-18-intermediate, and ≥19-high)]. Primary outcome included all-cause mortality at 30, 90 days, and 1 year. Multivariate Cox proportional hazards regression modeling was used to assess the independent association between Norton score and mortality. Net reclassification improvement (NRI) analysis was used to asses Norton's additive predictive ability upon known prognostic factors. RESULTS: Among 4388 study patients, 32% (n=1611) had low Norton score, 28% (n=1384) intermediate score, and 40% (n=1900) high score. Kaplan-Meier analysis demonstrated significantly higher 30-day mortality among patients with a low Norton score as compared with those with intermediate or high score (2.6%, 6.3%, and 16.1%; log rank p<0.001). A similar trend was noted at 90 days and 1 year. Multivariate analysis found Norton score to be an independent predictor of mortality with each one-point decrement associated with a significant 15% increased risk for 30-day mortality [HR=1.15 (95%CI, 1.12-1.17) p<0.001]. NRI analysis showed an improvement of 21.5% (95%CI 18.3-25.1%) predicting 1-year mortality. CONCLUSION: Our findings show that the admission Norton score is a powerful marker of short- and long-term mortality. These data suggest that the scale should be added as a risk stratification tool in this high-risk population.

Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study.

5-oxoprolinemia (pyroglutamic acid, PGA) in the absence of acetaminophen use has been rarely reported as a cause for high anion gap metabolic acidosis. We investigated the prevalence and risk factors for elevated PGA concentrations among hospitalized patients with high anion gap metabolic acidosis: We prospectively enrolled patients with high anion gap metabolic acidosis hospitalized in the department of medicine. For each patient we collected the main diagnosis, concurrent medications and laboratory parameters. Spot urine samples were tested for PGA concentration. Levels ≥63 µmol/mmol creatinine were considered elevated. Overall, forty patients were prospectively followed. Mean age was 66.9 (17.9) years. Four (6.3%) patients had a high urine PGA level and demonstrated also lower blood pH (7.2 vs 7.3, p = 0.05) and lower serum lactate concentration (17.5 mg/dl vs 23.0 mg/dl, p = 0.04). Additionally, the high PGA level group consisted of more patients with septic shock [2/4 (50%) vs 3/36 (8.3%)] with a trend towards significance (p = 0.07). In conclusion, PGA might have a role in patients with septic shock and acidosis. Being a treatable condition, PGA should be taken into consideration particularly when no other cause for high anion gap is identified.

Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family with a New Recessive Mutation (S553L) Compared to a Family with a Dominant Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter.

BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described. METHODS: Clinical and genetic investigation of members of 2 families was performed, one with recessive FHHt, and the other, an expansion of a family with Q309R KLHL3 dominant mutation, previously reported by us. Urinary exosomal sodium chloride cotransporter (NCC) was measured. RESULTS: A family with recessive FHHt caused by a new KLHL3 mutation, S553L, is described. This consanguineous Jewish family of Yemenite extraction, included 2 homozygous and 7 heterozygous affected subjects. Increased urinary NCC was found in the affected members of the family with dominant Q309R KLHL3 mutation. In the recessive S553L family, homozygotes appeared to have increased urinary NCC abundance. Surprisingly, heterozygotes seemed to have also increased urinary NCC, though at an apparently lower degree. This was not accompanied by a clinical phenotype. CONCLUSIONS: A new recessive mutation in KLHL3 (S553L) was identified in FHHt. Increased urinary NCC was found in affected members (heterozygous) with dominant KLHL3 Q309R, and in affected members (homozygous) of the recessive form. Unexpectedly, in the recessive disease, heterozygotes seemed to have increased urinary NCC as well, apparently not sufficient quantitatively to produce a clinical phenotype.