Interventricular septal thickness on cardiac computed tomography as a novel risk factor for conduction disturbances in patients undergoing transcatheter aortic valve replacement.

AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10 mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52 mm vs. 3.38 ± 0.52 mm, 4.10 ± 1.02 mm vs. 4.65 ± 0.78 mm, 6.11 ± 1.12 mm vs. 6.88 ± 1.03 mm, and 9.72 ± 1.95 mm vs. 10.70 ± 1.55 mm for 1, 2, 5 and 10 mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4 mm at 2 mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.

Transcatheter Aortic Valve Replacement in Patients With Reduced Ejection Fraction and Nonsevere Aortic Stenosis.

BACKGROUND: The potential benefit of transcatheter aortic valve replacement (TAVR) in patients with nonsevere aortic stenosis (AS) and heart failure is controversial. This study aimed to assess outcomes of patients with nonsevere low-gradient AS (LGAS) and reduced left ventricular ejection fraction undergoing TAVR or medical management. METHODS: Patients undergoing TAVR for LGAS and reduced left ventricular ejection fraction (<50%) were included in a multinational registry. True-severe low-gradient AS (TS-LGAS) and pseudo-severe low-gradient AS (PS-LGAS) were classified according to computed tomography-derived aortic valve calcification thresholds. A medical control group with reduced left ventricular ejection fraction and moderate AS or PS-LGAS was used (Medical-Mod). Adjusted outcomes between all groups were compared. Among patients with nonsevere AS (moderate or PS-LGAS), outcomes after TAVR and medical therapy were compared using propensity score-matching. RESULTS: A total of 706 LGAS patients undergoing TAVR (TS-LGAS, N=527; PS-LGAS, N=179) and 470 Medical-Mod patients were included. After adjustment, both TAVR groups showed superior survival compared with Medical-Mod patients (all P<0.001), while no difference was found between TS-LGAS and PS-LGAS TAVR patients (P=0.96). After propensity score-matching among patients with nonsevere AS, PS-LGAS TAVR patients showed superior 2-year overall (65.4%) and cardiovascular survival (80.4%) compared with Medical-Mod patients (48.8% and 58.5%, both P≤0.004). In a multivariable analysis including all patients with nonsevere AS, TAVR was an independent predictor of survival (hazard ratio, 0.39 [95% CI, 0.27-0.55]; P<0.0001). CONCLUSIONS: Among patients with nonsevere AS and reduced left ventricular ejection fraction, TAVR represents a major predictor of superior survival. These results reinforce the need for randomized-controlled trials comparing TAVR versus medical management in heart failure patients with nonsevere AS. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04914481.

Noninvasive Hemodynamic Evaluation Following TAVI for Severe Aortic Stenosis.

Background Various hemodynamic changes occur following transcatheter aortic valve implantation (TAVI) that may impact therapeutic decisions. NICaS is a noninvasive bioimpedance monitoring system aimed at hemodynamic assessment. We used the NICaS system in patients with severe aortic stenosis (AS) to evaluate short-term hemodynamic changes after TAVI. Methods and Results We performed hemodynamic analysis using NICaS on 97 patients with severe AS who underwent TAVI using either self-expandable (68%) or balloon-expandable (32%) valves. Patients were more often women (54%) and had multiple comorbidities including hypertension (83%), coronary artery disease (46%), and diabetes (37%). NICaS was performed at several time points-before TAVI, soon after TAVI, at hospital discharge, and during follow-up. Compared with baseline NICaS measurements, we observed a significant increase in systolic blood pressure and total peripheral resistance (systolic blood pressure 132±21 mm Hg at baseline versus 147±23 mm Hg after TAVI, P<0.001; total peripheral resistance 1751±512 versus 2084±762 dynes*s/cm5, respectively, P<0.001) concurrent with a decrease in cardiac output and stroke volume (cardiac output 4.2±1.5 versus 3.9±1.3 L/min, P=0.037; stroke volume 61.4±14.8 versus 56.2±15.9 mL, P=0.001) in the immediate post-TAVI period. At follow-up (median 59 days [interquartile range, 40.5-91]) these measurements returned to values that were not different from the baseline. A significant improvement in echocardiography-based left ventricular ejection fraction was observed from baseline to follow-up (55.6%±11.6% to 59.4%±9.4%, P<0.001). Conclusions Unique short-term adaptive hemodynamic changes were observed using NICaS in patients with AS soon after TAVI. Noninvasive hemodynamic evaluation immediately following TAVI may contribute to the understanding of complex hemodynamic changes and merits favorable consideration.

The short and long-term characteristics and outcomes of patients with grade 1 myocardial uptake on cardiac scintigraphy.

AIMS: This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) requiring further invasive investigation with tissue biopsy. METHODS AND RESULTS: We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR-CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re-evaluation for ATTR-CA at long term. Of the 132 ATTR-CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light-chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR-CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow-up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re-evaluated at a median follow-up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long-term scintigraphy. CONCLUSIONS: Patients with suspected ATTR-CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long-term follow-up. Larger studies should define the optimal evaluation strategy in this population.

Thrombogenicity and endothelial progenitor cells function during Acute myocardial infarction - comparison of Prasugrel versus Ticagrelor.

BACKGROUND: Thrombin generation (TG), platelet function and circulating endothelial progenitor cells (EPCs) have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y12 inhibitors on these aspects has mostly been studied in the sub-acute phase following myocardial infarction. OBJECTIVES: Comparing the effects of prasugrel and ticagrelor on TG and EPCs in the acute phase of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPCs were evaluated prior to P2Y12 inhibitor loading dose (T0), and one day following (T1). RESULTS: Between December 2018 - July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N = 42) or prasugrel (N = 41) treatment. No differences were observed at T0 for all measurements. P2Y12 reactivity units (PRU) at T1 did not differ as well (prasugrel 13.2 [5.5-20.8] vs. ticagrelor 15.8 [4.0-26.3], p = 0.40). At T1, prasugrel was a significantly more potent TG inhibitor, with longer lag time to TG initiation (7.7 ± 7.5 vs. 3.9 ± 2.1 min, p < 0.01), longer time to peak (14.1 ± 12.6 vs. 8.3 ± 9.7 min, p = 0.03) and a lower endogenous thrombin potential (AUC 2186.1 ± 1123.1 vs. 3362.5 ± 2108.5 nM, p < 0.01). Furthermore, EPCs measured by percentage of cells expressing CD34 (2.6 ± 4.1 vs. 1.1 ± 1.1, p = 0.01) and CD133 (2.3 ± 1.8 vs. 1.4 ± 1.5, p = 0.01) and number of colony forming units (CFU, 2.1 ± 1.5 vs. 1.1 ± 1.0, p < 0.01) were significantly higher in the prasugrel group. CONCLUSION: Among STEMI patients, prasugrel as compared to ticagrelor was associated with more potent TG inhibition and improved EPCs count and function.

Reticulated Platelets and Their Relationship with Endothelial Progenitor Cells during the Acute Phase of ST-Elevation Myocardial Infarction.

Introduction: Endothelial progenitor cells (EPC) and reticulated platelets (RP) have central roles in the thrombotic and angiogenetic interactions during ST-elevation myocardial infarction (STEMI). The EPC and RP response in patients with STEMI treated by primary percutaneous intervention (PPCI) has not yet been investigated. Methods: We assessed EPC quantification by the expression of CD133+ and CD34+, and EPC function by the capacity of the cells to form colony-forming units (CFU) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) during the acute phase of STEMI. These measurements were correlated with RP at baseline and after 24 h following PPCI. Results: Our cohort included 89 consecutive STEMI-diagnosed patients enrolled between December 2018 and July 2021. At baseline, there was a strong positive correlation between reticulated platelet quantity and MTT levels (R = 0.766 and R2 = 0.586, p < 0.001), CD34+ levels (R = 0.602, and R2 = 0.362, p < 0.001); CD133+ levels (R = 0.666 and R2 = 0.443, p < 0.001) and CFU levels (R = 0.437, R2 = 0.191, p < 0.001). The multiple linear regression showed that levels of MTT (adjusted R2 = 0.793; p < 0.001), CD34+ and CD133+ (adjusted R2 = 0.654; p < 0.001 and adjusted R2 = 0.627; p < 0.001, respectively) had strong independent correlations with RP response. At 24 h after PPCI, the correlation between RP quantity and EPC markers was not significant, except for MTT levels (R = 0.465, R2 = 0.216, p < 0.001). Conclusions: In patients with STEMI, higher levels of RP at baseline are significantly correlated with a more potent EPC response. The translational significance of these findings needs further investigation.

Myocarditis following COVID-19 vaccination in adolescents: Cardiac magnetic resonance imaging study.

Introduction: Vaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12-15. Objectives: To describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12-15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine. Methods: CMR of adolescents (age 12-15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed. Results: A total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13-15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192-229, range 179-233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27-149). The median left ventricular ejection fraction was within normal range 65% (range 62-69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0-6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3-5 mm) at end-systole. Conclusions: CMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

Management and outcomes over time of acute coronary syndrome patients at particularly high cardiovascular risk : the ACSIS registry-based retrospective study.

OBJECTIVE: Some patients following acute coronary syndrome (ACS) are at particularly increased risk for recurrent cardiovascular events. We aimed to examine temporal trends in the management and outcomes across the spectrum of these particularly high-risk patients. DESIGN AND SETTING: A retrospective study based on the ACS Israeli survey (ACSIS) registry, a multicentre prospective national registry, taking place biennially in 25 cardiology departments in Israel. Temporal trends were examined in the early (2002-2008) and late (2010-2018) time periods. PARTICIPANTS: Consecutive patients with ACS enrolled in the ACSIS registry were stratified according to the Thrombolysis in Myocardial Infarction Risk Score for secondary prevention (TRS2°P) to high (TRS2°p=3), very high (TRS2°p=4) or extremely high risk (TRS2°p=5-9). Patients with TRS2°p<3 were excluded. From the initial 15 196 patients enrolled, 5359 patients were eventually included.Clinical outcome measures included 30-day major adverse cardiovascular events (MACE) and 1-year mortality. RESULTS: Among 5359 patients (50% high risk, 30% very high risk and 20% extremely high risk), those with a higher risk were older, had more comorbidities, presented more with non-ST elevation myocardial infarction, and were treated less often with guideline-recommended pharmacotherapy and percutaneous coronary intervention. Over time, treatment has improved in all risk strata, and the rate of 30-day MACE has significantly decreased in all risk groups (from 21% to 10%, from 22% to 15%, and from 26% to 16%, in high, very high and extremely high-risk groups, respectively, p<0.001 for each). However, 1-year mortality decreased only among high and very high-risk patients, and not among extremely high-risk patients in whom 1-year mortality rates remained very high (28.7% vs 28.9%, p=1). CONCLUSION: Within a particularly high-risk cohort of patients with ACS, treatment has significantly progressed over almost 2 decades. While short-term outcomes have improved in all risk groups, 1-year mortality has remained unchanged in extremely high-risk patients with ACS.

Relation of Serum Albumin Levels to Myocardial Extracellular Volume in Patients With Severe Aortic Stenosis.

Severe aortic stenosis (AS) is often characterized by myocardial interstitial fibrosis. Myocardial interstitial fibrosis, classically measured by magnetic resonance imaging, was also shown to be accurately measured by computed tomography (CT)-derived extracellular volume fraction (ECVF). Serum albumin (SA) level (g/dl) has been shown to correlate with ECVF among patients with heart failure and preserved ejection fraction. Our objective was to evaluate the association between SA and ECVF among patients with severe symptomatic AS. Patients with symptomatic severe AS who were evaluated as candidates for intervention between 2016 and 2018 were enrolled prospectively. All patients underwent precontrast and postcontrast CT for estimating myocardial ECVF. Valid ambulatory SA within 6 weeks of the cardiac CT were obtained and classified as (tertiles) <3.8, 3.8 to 4.19, and ≥4.2 g/dl. Patients with acute systemic illness at the time of the albumin test were excluded. The study included 68 patients, mean age 81 ± 6 years, 53% women. Patients with lower SA were more likely to have chronic renal failure, previous percutaneous coronary interventions, and a reduced functional class. The mean ECVF (%) in the study cohort was 41 ± 12%, significantly higher among the patients in the lower SA level groups (50 ± 12% vs 38 ± 7% vs 33 ± 9% in the <3.8 g/dl, 3.8 to 4.19 g/dl and ≥4.2 g/dl groups respectively, p for trend <0.001). A statistically significant inverse correlation was found between SA levels and ECVF (r -0.7, p <0.001). Multivariable analysis showed significant independent association between low SA and ECVF. In conclusion, the SA level is inversely associated with CT-derived ECVF in patients with severe AS.

Myocarditis following COVID-19 vaccination: magnetic resonance imaging study.

AIMS: To describe the cardiac magnetic resonance (CMR) imaging findings of patients who developed myocarditis following messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination. METHODS AND RESULTS: The present study retrospectively evaluated patients with clinically adjudicated myocarditis within 42 days of the first Pfizer-BNT162b2 mRNA COVID-19 vaccination, between 20 December 2020 and 24 May 2021 who underwent CMR. A total of 15 out 54 patients (28%) with myocarditis underwent a CMR and were included, 100% males, median age of 32 years (interquartile range = 22.5-40). Most patients presented with chest pain (87%) and had an abnormal electrocardiogram (79%). The severity of the disease was mild in 67% and intermediate in 33%. All patients survived and one patient was readmitted during the study period. CMR was performed at a median of 65 days (range 3-130 days) following diagnosis. Median ejection fraction was 58% (range 51-74%) global- and regional wall motion abnormalities were present in one and three patients, respectively. Native T1 was available in 13/15 patients (2/3 in 3 T and 11/12 in the 1.5 T), with increased values among 6/13. Late gadolinium enhancement (LGE) was found among 13/15 patients with a median of 2% (range 0-15%) with inferolateral wall being the most common location (8/13). The patterns of the LGE were: mid-wall in six patients; epicardial in five patients; and mid-wall and epicardial in two patients. CONCLUSIONS: Among patients who were diagnosed with post-vaccination clinical myocarditis, CMR imaging findings are mild and consistent with 'classical myocarditis'. The short-term clinical course and outcomes were favourable.

Albumin as a Prognostic Marker for Atrial Fibrillation Recurrence following Cryoballoon Ablation of Pulmonary Venous.

Introduction: Atrial fibrillation (AF) recurrence following pulmonary vein isolation (PVI) ablation has clinical significance. Identifying risk factors for AF recurrence is important. We investigated serum albumin (SA) levels (g/dL) as a prognostic factor for the recurrence of AF following cryoballoon PVI ablation. Methods: We included patients who underwent cryoballoon PVI ablation at our institution between the years 2013 and 2018. The primary outcome was recurrence of AF during follow up. Results: Our cohort consisted of 126 patients (67% males, mean age 61.8 ± 10.0 years). The pattern of AF amongst the cohort was paroxysmal in 62.5%, persistent in 25.4%, and longstanding persistent in 6.3%. Those with lower SA levels had a mean AF duration significantly less than those with higher SA levels (2.81 years, 7.34 years, and 6.37 years for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p = 0.003). Patients with lower SA levels were significantly more likely to have had more previous cardioversions and a larger left atrial area and volume. The mean follow-up was 380 days, in which the AF recurrence rate was 20.6%. Patients with lower SA level had significantly more AF recurrences (47.4%, 16.7%, and 2.2% for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p < 0.001). Upon multivariate analysis, an SA level < 3.8 was associated with a higher risk of AF recurrence (OR = 5.422 95% CI 1.134; 25.910; p < 0.001). Conclusion: SA levels were found to be a strong independent marker for AF recurrence following PVI ablation.

Severe aortic stenosis echocardiographic thresholds revisited.

BACKGROUND: In view of inconsistencies in threshold values of severe aortic stenosis (AS) hemodynamic indices, it is unclear what is the relative contribution of each variable in a binary classification of AS based on aortic valve replacement (AVR) indication. We aimed to assess relative discriminative value and optimal threshold of each constituent hemodynamic parameter for this classification and confirm additional prognostic value. METHODS: Echocardiography studies of 168 patients with ≥ moderate AS were included. AS types were dichotomized into Group-A, comprising moderate and Normal-Flow Low-Gradient (NFLG), and Group-B, comprising High-Gradient(HG), Low Ejection Fraction Low-Flow Low-Gradient(Low EF-LFLG), and Paradoxical Low-Flow Low-Gradient(PLFLG) AS. Aortic valve area (AVA), Doppler velocity index (DVI), peak aortic velocity, mean gradient, stroke volume index and transaortic flow rate(TFR) were assessed for A/B Group discrimination value and optimal thresholds were determined. Dichotomized values were assessed for predictive value for AVR or death. RESULTS: C-statistic values for binary AS classification was .74-.9 for the tested variables. AVA and DVI featured the highest score, and SVI the lowest one. AVA≤.81 cm2 and DVI≤.249 had 87.6% and 86% respective sensitivity for Group B patients, and a similar specificity of 80.9%. During a mean follow-up of 9.1±10.1 months, each of the tested dichotomized variables except for SVI predicted AVR or death on multivariate analysis. CONCLUSION: An AVA value ≤.81 cm2 or a DVI ≤ .249 threshold carry the highest discriminative value for severe AS in patients with aortic stenosis, translating into an independent prognostic value, and can be helpful in making clinical decisions.

Myocarditis after Covid-19 Vaccination in a Large Health Care Organization.

BACKGROUND: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored. METHODS: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose. RESULTS: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function. CONCLUSIONS: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Management and outcome across the spectrum of high-risk patients with myocardial infarction according to the thrmobolysis in myocardial infarction (TIMI) risk-score for secondary prevention.

BACKGROUND: Patients with myocardial infarction (MI) are at increased risk for recurrent cardiovascular events, yet some patients, such as the elderly and those with prior comorbidities, are particularly at the highest risk. Whether these patients benefit from contemporary management is not fully elucidated. METHODS: Included were consecutive patients with MI who underwent percutaneous coronary intervention (PCI) in a large tertiary medical center. Patients were stratified according to the thrombolysis in myocardial infarction (TIMI) risk score for secondary prevention (TRS2°P) to high (TRS2°P = 3), very high (TRS2°P = 4), or extremely high-risk (TRS2°P = 5-9). Excluded were low and intermediate-risk patients (TRS2°P < 3). Outcomes included 30-day/1-year major adverse cardiac events (MACE) and 1-year mortality. Temporal trends were examined in the early (2004-2010) and late (2011-2016) time-periods. RESULTS: Among 2053 patients, 50% were high-risk, 30% very high-risk and 20% extremely high-risk. Extremely high-risk patients were older (age 74 ± 10 year) and had significant comorbidities (chronic kidney disease 68%, prior CABG 40%, heart failure 78%, peripheral artery disease 29%). Drug-eluting stents and potent antiplatelets were more commonly used over time in all risk-strata. Over time, 30-day MACE rates have decreased, mainly attributed to the very high (11.3% to 5.1%, p = .006) and extremely high-risk groups (15.9% to 8.0%, p = .016), but not the high-risk group, with similar quantitative results for 1-year MACE. The rates of 1-year mortality remained unchanged in either group. CONCLUSION: Within a particularly high-risk cohort of MI patients who underwent PCI, the implementation of guideline-recommended therapies has improved over time, with the highest-risk groups demonstrating the greatest benefit in outcomes.

Dysfunctional endothelial progenitor cells in patients with Hodgkin's lymphoma in complete remission.

BACKGROUND: Patients with a history of Hodgkin's lymphoma (HL) are at increased long-term risk of cardiovascular morbidity and mortality. Studies report an association between the pathophysiology of coronary artery disease (CAD) and levels of circulating endothelial progenitor cells (EPC), which play an essential role in vascular injury repair. The aim of the present study was to investigate the potential involvement of abnormal EPC level or function in the CAD risk of survivors of HL in remission. METHODS: EPCs were isolated from peripheral blood samples drawn from 4 groups of patients aged 20-50 years with no history of CAD: 17 patients with HL who had been in complete remission for at least 2 years, four newly diagnosed patients with HL before treatment, 28 patients with diabetes all attending a tertiary medical center, and 16 healthy individuals. Levels of EPC surface markers were measured by flow cytometry, and EPC function was evaluated by the number of colony-forming units (CFUs) and MTT assay. RESULTS: Levels of circulating CD34(+)/VEGFR2(+) and CD133(+)/VEGFR2(+) were significantly higher in the newly diagnosed untreated patients with HL compared to the patients with HL in remission (P = 0.03 and P = 0.005, respectively), in the patients in remission compared to the patients with diabetes (P = 0.011 and P < 0.001, respectively), and in the patients in remission compared to the healthy individuals (P = 0.08 and P = 0.003, respectively). The analysis of cell viability and the number of colony-forming units in the patients with HL in remission yielded significant differences from the healthy group (P = 0.005 and P < 0.001, respectively) but not from either the newly diagnosed patients with HL or the diabetic patients. CONCLUSIONS: These results suggest that patients in complete remission of HL for at least 2 years have an abnormal EPC profile characterized by high circulating levels but attenuated function.

Clinical characteristics and survival of patients with diabetes mellitus following non-traumatic lower extremity amputation.

BACKGROUND: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life. OBJECTIVES: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients. METHODS: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009. RESULTS: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs. 45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04-1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01-1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26-2.24, P < 0.001) significantly increased one year mortality risk. CONCLUSIONS: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.