Endothelial function predicts 5-year adverse outcome in patients hospitalized in an emergency department chest pain unit.

BACKGROUND: Although endothelial function is a marker for cardiovascular risk, endothelial dysfunction assessment is not routinely used in daily clinical practice. A growing challenge has emerged in identifying patients prone to cardiovascular events. We aim to investigate whether abnormal endothelial function may be associated with adverse 5-year outcomes in patients presenting to a chest pain unit (CPU). METHODS: Following endothelial function testing using EndoPAT 2000 in 300 consecutive patients without a history of coronary artery disease, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability. RESULTS: Mean 10-year Framingham risk score (FRS) was 6.6 ±â€Š5.9%; mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 7.1 ±â€Š7.2%; median reactive hyperemia index (RHI) as a measure of an endothelial function 2.0 and mean was 2.0 ±â€Š0.4. During a 5-year follow-up, the 30 patients who developed major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions, had higher 10-year FRS (9.6 ±â€Š7.8 vs. 6.3 ±â€Š5.6%; P  = 0.032), higher 10-year ASCVD risk (10.4 ±â€Š9.2 vs. 6.7 ±â€Š6.9%; P  = 0.042), lower baseline RHI (1.6 ±â€Š0.5 vs. 2.1 ±â€Š0.4; P  < 0.001) and a greater degree of coronary atherosclerotic lesions (53 vs. 3%, P  < 0.001) on CCTA compared with patients without MACE. Multivariate analysis demonstrated that RHI below the median was an independent predictor of 5-year MACE (odds ratio 5.567, 95% confidence interval 1.955-15.853; P  = 0.001). CONCLUSION: Our findings suggest that noninvasive endothelial function testing may contribute to clinical efficacy in triaging patients in the CPU and in predicting 5-year MACE. CLINICAL TRIALSGOV IDENTIFIER: NCT01618123.

Sex differences of patients with acute chest pain evaluated through a chest pain unit.

BACKGROUND: Although sex disparities between patients with acute myocardial infarction are well known, the data regarding sex differences among symptomatic patients with acute chest pain (ACP) are limited. METHODS: We retrospectively evaluated the records of 1000 consecutive patients with ACP and hospitalized in a tertiary medical center chest pain unit (CPU). Patients were divided according to sex. The primary outcome was defined as a composite end point of readmission because of chest pain, incidence of acute coronary syndrome, revascularization, and death at 90 days and 1 year. RESULTS: Overall, 673 men and 327 women were included in the current analysis. There was no difference in regard to sex for patients who underwent noninvasive evaluation, (87.8 vs. 87.3%, P  = 0.85, for female vs. male, respectively). Among patients who underwent coronary computed tomography angiography, women were less likely to have significant coronary artery disease (CAD) (4.2 vs. 11.3%, P  = 0.005). Similarly, women had fewer significant findings (4.4 vs. 7.6%, P  = 0.007) on myocardial perfusion imaging. Consequently, fewer women underwent angiography (8 vs. 14%, P  = 0.006) and revascularization (2.8 vs. 7.3%, P  = 0.004). During follow-up, sex was not associated with the development of the primary composite outcome [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.39-2.09, P -value = 0.82 and OR 1.16, 95% CI 0.65-2.06, P -value = 0.59 for 90-day and 1-year follow-up, respectively]. CONCLUSION: Evaluation of patients through a CPU enables comparable noninvasive evaluation, appropriate utilization of invasive assessment with similar outcomes during the short and intermediate follow-up period regardless of patients' sex.

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.

Poor outcome among patients undergoing myocardial perfusion imaging with intermediate-zone troponin.

BACKGROUND: Intermediate zone troponin elevation is defined as one to five times the upper limit of normal. Approximately half the patients presenting with chest pain to the emergency department have initial intermediate zone troponin. OBJECTIVES: We aimed to investigate the long-term outcome of patients hospitalized with chest pain and intermediate zone troponin elevation. METHODS: We investigated 8269 patients hospitalized in a tertiary center with chest pain. All patients had serial measurements of troponin during hospitalization. Patients were divided into three groups based on their initial troponin levels: negative troponin (N = 6112), intermediate zone troponin (N = 1329) and positive troponin (N = 828). All patients underwent myocardial perfusion imaging (MPI) as part of the initial evaluation. RESULTS: Mean age of the study population was 68 ± 11, of whom 36% were women. Patients with an intermediate zone troponin were older, more likely to be males, and with significantly more cardiovascular co-morbidities. Multivariate analysis adjusted for age, gender, cardiovascular risk factors, and abnormal MPI result found that patients with intermediate zone troponin had a 70% increased risk of re-hospitalization at 1 year (HR 1.70, 95%CI 1.48-1.96, p-value < 0.001) and 5.3 times higher risk of total mortality at 1-year (HR 5.33, 95%CI 3.65-7.78, p-value < 0.001). sub-group analysis found that among the intermediate zone troponin group, patients with double intermediate zone troponin had the poorest outcome. CONCLUSIONS: Intermediate zone troponin elevation is an independent risk factor associated with adverse outcomes and therefore patients with an initial value in this range should be closely monitored and aggressively managed.

CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome.

BACKGROUND: Platelet function testing (PFT) in patients treated with P2Y12 inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients. METHODS: Two hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0-1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2-6, 2-9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19-46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity. RESULTS: Low CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both]. CONCLUSION: In ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings' clinical implications.

Early post-stress decrease in cardiac performance by impedance cardiography and its relationship to the severity and extent of ischemia by myocardial perfusion imaging.

BACKGROUND: While single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia. METHODS: Prospectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia. RESULTS: In the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index (19.2, 29.1, 90.5 and 107%, respectively) compared with the second group (- 2.7, 3.8, 43.7 and 53.5%, respectively), as well as a significantly greater decrease in total peripheral resistance index (- 38.7% compared with - 16.3%), with corresponding p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively. CONCLUSIONS: Our data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia.

Trends in long-term prognosis according to left ventricular ejection fraction after acute coronary syndrome.

AIMS: Our aim was to investigate trends in prognosis among survivors of acute coronary syndrome according to left ventricular ejection fraction during a 16-year period. METHODS: Data were derived from the Acute Coronary Syndrome Israeli Survey during the years 2000-2016. Patients aged 18 years and older were included in the analysis (N=11,725). Patients were classified into two groups based on their left ventricular ejection fraction: preserved (≥50%) and reduced (<50%) and also according to their acute coronary syndrome onset (2000-2006 early period vs. 2008-2016 late period). Endpoints were all-cause mortality rates at one and three years after the index event. RESULTS: Preserved left ventricular ejection fraction was present in 5047/11,725 (43%) of patients. As expected, patients with preserved left ventricular ejection fraction had lower 1 and 3-year mortality rates as compared with reduced left ventricular ejection fraction regardless of the acute coronary syndrome period onset (6% vs. 19%, p<0.001). Nevertheless, in the late period the prevalence of reduced left ventricular ejection fraction decreased significantly, becoming equal to preserved left ventricular ejection fraction [2761 (50.5%) vs. 2713 (49.5%) respectively, p=0.3]. Moreover, prognosis during the late period as compared with the early period was improved only in patients with reduced left ventricular ejection fraction (HR 0.79; 95% CI 0.70-0.89, p=0.0001). CONCLUSION: The prevalence of reduced left ventricular ejection fraction has decreased and prognosis has improved during the past several years but is still much worse than the prognosis of preserved left ventricular ejection fraction.

The efficacy and safety of evaluating elderly patients using a comprehensive diagnostic protocol via a chest pain unit.

Elderly patients are often excluded from a chest pain unit (CPU)-based evaluation of chest pain due to concern about adverse events and poorer outcomes. The aim of this study was to assess the feasibility and safety of thoroughly evaluating elderly patients ≥ 65 years of age presented with acute chest pain via a CPU. We evaluated 1220 consecutive patients admitted to our CPU, and stratified them according to age: those over and those under 65 years. Patients were evaluated for outcomes during hospitalization and for a composite endpoint at 60 days post discharge which included: recurrent hospitalization due to chest pain, need for coronary revascularization, acute coronary syndrome, and death. Overall, 241 (20%) patients were in the ≥ 65-year-old group and 979 (80%) patients in the group < 65 years of age. Older patients were more likely to be female, have more co-morbidities, and a history of prior coronary artery disease. There was no difference between the two groups regarding in-hospital course, including hospitalization in the CPU (9.5% vs. 11.6%, p = 0.37), coronary angiography (7.9% vs. 9.8%, p = 0.37), and revascularization performed during the evaluation period (4.5% vs. 3.3%, p = 0.42). Of those discharged, the primary endpoint at 60 days was observed in 11 (1.5%) and 7 (3.9%) patients in those under and over 65 years, respectively, (p = 0.13). No mortalities were recorded. Comprehensive evaluation via a CPU of patients who are ≥ 65 years of age is feasible and safe with in-hospital and short-term outcomes compared to their younger counterparts.

Heart Rate Variability for Risk Assessment of Myocardial Ischemia in Patients Without Known Coronary Artery Disease: The HRV-DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) Study.

Background Detecting significant coronary artery disease (CAD) in the general population is complex and relies on combined assessment of traditional CAD risk factors and noninvasive testing. We hypothesized that a CAD-specific heart rate variability (HRV) algorithm can be used to improve detection of subclinical or early ischemia in patients without known CAD. Methods and Results Between 2014 and 2018 we prospectively enrolled 1043 patients with low to intermediate pretest probability for CAD who were screened for myocardial ischemia in tertiary medical centers in the United States and Israel. Patients underwent 1-hour Holter testing, with immediate HRV analysis using the HeartTrends DyDx algorithm, followed by exercise stress echocardiography (n=612) or exercise myocardial perfusion imaging (n=431). The threshold for low HRV was identified using receiver operating characteristic analysis based on sensitivity and specificity. The primary end point was the presence of myocardial ischemia detected by exercise stress echocardiography or exercise myocardial perfusion imaging. The mean age of patients was 61 years and 38% were women. Myocardial ischemia was detected in 66 (6.3%) patients. After adjustment for CAD risk factors and exercise stress testing results, low HRV was independently associated with a significant 2-fold increased likelihood for myocardial ischemia (odds ratio, 2.00; 95% CI, 1.41-2.89 [P=0.01]). Adding HRV to traditional CAD risk factors significantly improved the pretest probability for myocardial ischemia. Conclusions Our data from a large prospective international clinical study show that short-term HRV testing can be used as a novel digital-health modality for enhanced risk assessment in low- to intermediate-risk individuals without known CAD. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT01657006, NCT02201017).

Differences in Mortality of New-Onset (De-Novo) Acute Heart Failure Versus Acute Decompensated Chronic Heart Failure.

Minimal attention has been paid to understanding the implications of the chronicity of heart failure (HF) diagnosis on prognosis of hospitalized patients with acute HF (AHF). We aimed to assess the differences in outcomes between hospitalized patients with AHF that are new-onset (de-novo) AHF and acutely decompensated chronic HF (ADCHF). We analyzed data of 2,328 patients with AHF, who were enrolled in the HF survey in Israel. Patients were classified into de-novo AHF and ADCHF. A total of 721 (31%) patients were classified as de-novo AHF and 1,607 (69%) patients were classified as ADCHF. Patients with de-novo AHF were more likely to be younger, with fewer co-morbidities represented by lower Charlson index, and less likely to have past myocardial infarction as well as coronary revascularization. At 30 days mortality rates were similar in both groups (9% vs 8% in de-novo AHF and ADCHF, respectively). Survival analysis showed that at 1 and 10 years the all-cause mortality rates were significantly higher in patients with ADCHF (33% vs 22% and 90% vs 72%, 1 and 10 years, log-rank p < 0.001, respectively). Consistently, multivariable analysis showed that patients with ADCHF had an independently 58% and 48%, higher mortality risk at 1 and 10 years, respectively, (1-year hazard ratio = 1.58; 95% confidence interval 1.05 to 2.38, p = 0.03; 10-year hazard ratio = 1.48; 95% confidence interval = 1.23 to 2.77; p < 0.001). In conclusion, previous history of HF is an independent predictor of 1-year and 10-year mortality after hospitalization for AHF. Distinction between de-novo AHF and ADCHF may improve our understanding and risk stratification of patients with AHF.

The Association of Body Mass Index and 20-Year All-Cause Mortality Among Patients With Stable Coronary Artery Disease.

BACKGROUND: Limited data exist regarding the long-term association of body mass index (BMI) and all-cause mortality among patients with stable coronary artery disease (CAD). Accordingly, the aim of this study is to explore the association between BMI and long-term all-cause mortality among patients with stable CAD. METHODS: Our study included 15,357 patients with stable CAD who were enrolled in the Bezafibrate Infarction Prevention (BIP) registry between February, 1990 and October1992, and subsequently followed-up through December 2014. RESULTS: 5,051 (33%) patients were classified as normal weight (BMI 18.5-24.99kg/m2), while 7,841 (51%) patients were classified as overweight (BMI 25-29.99kg/m2), and 2,465 (16%) as obese (BMI≥30). Kaplan-Meier survival analysis showed that at 20 years of follow-up the rate of all-cause mortality was significantly higher among obese patients (67%) compared to overweight (61%) and normal weight (61%); log rank p-value for the overall difference <0.001. Multivariable analysis showed that obese patients had an independently 12% greater mortality risk compared to normal weight patients (HR=1.12; 95% CI 1.02-1.23; p=0.02), whereas, overweight patients experienced a similar mortality risk as normal weight patients (HR=0.99; 95% CI 0.92-1.06; p=0.76). The mortality risk associated with obesity was pronounced among patients younger than 65 years (p-value for interaction<0.05). CONCLUSIONS: Our findings indicate that obesity is independently associated with increased risk for long-term mortality among patients with stable coronary artery disease, whereas overweight does not appear to confer an additional risk in this population.

Feasibility study of a novel general purpose CZT-based digital SPECT camera: initial clinical results.

BACKGROUND: The performance of a prototype novel digital single-photon emission computed tomography (SPECT) camera with multiple pixelated CZT detectors and high sensitivity collimators (Digital SPECT; Valiance X12 prototype, Molecular Dynamics) was evaluated in various clinical settings. Images obtained in the prototype system were compared to images from an analog camera fitted with high-resolution collimators. Clinical feasibility, image quality, and diagnostic performance of the prototype were evaluated in 36 SPECT studies in 35 patients including bone (n = 21), brain (n = 5), lung perfusion (n = 3), and parathyroid (n = 3) and one study each of sentinel node and labeled white blood cells. Images were graded on a scale of 1-4 for sharpness, contrast, overall quality, and diagnostic confidence. RESULTS: Digital CZT SPECT provided a statistically significant improvement in sharpness and contrast in clinical cases (mean score of 3.79 ± 0.61 vs. 3.26 ± 0.50 and 3.92 ± 0.29 vs. 3.34 ± 0.47 respectively, p < 0.001 for both). Overall image quality was slightly higher for the digital SPECT but not statistically significant (3.74 vs. 3.66). CONCLUSION: CZT SPECT provided significantly improved image sharpness and contrast compared to the analog system in the clinical settings evaluated. Further studies will evaluate the diagnostic performance of the system in large patient cohorts in additional clinical settings.

The prognostic significance of improvement in exercise capacity in heart failure patients who participate in cardiac rehabilitation programme.

Introduction There are limited contemporary data regarding the association between improvement in cardiovascular fitness in heart failure patients who participate in a cardiac rehabilitation programme and the risk of subsequent hospitalisations. Methods The study population comprised 421 patients with heart failure who participated in our cardiac rehabilitation programme between the years 2009 and 2016. All were evaluated by a standard exercise stress test before initiation, and underwent a second exercise stress test on completion of 3 ± 1 months of training. Participants were dichotomised by fitness level at baseline, according to the percentage of predicted age and sex norms achieved. Each group was further divided according to its degree of functional improvement, between the baseline and the follow-up exercise stress test. Major improvement was defined as improvement above the median value in each group. The combined primary endpoint was cardiac hospitalisation or all-cause mortality. Results A total of 211 (50%) patients had low baseline fitness (<73% (median)) for age and sex-predicted metabolic equivalents of task value. Compared to patients with higher fitness, those with a low baseline fitness were more commonly smokers, had diabetes and were obese ( P < 0.05 for all). Multivariable Cox proportional hazard regression analysis showed that, independent of baseline capacity, an improvement of 5% of predicted fitness was associated with a corresponding 10% reduced risk of cardiac hospitalisation or all-cause mortality ( P < 0.001). Conclusion In heart failure patients participating in a cardiac rehabilitation programme, improved cardiovascular fitness is associated with reduced mortality or cardiac hospitalisation risk during long-term follow-up, independent of baseline fitness.

Impaired Fasting Glucose Is the Major Determinant of the 20-Year Mortality Risk Associated With Metabolic Syndrome in Nondiabetic Patients With Stable Coronary Artery Disease.

BACKGROUND: We wanted to explore the association of metabolic syndrome (MetS) versus its individual components with 20-year all-cause mortality among patients with stable coronary artery disease. METHODS AND RESULTS: The cohort comprised 12 403 nondiabetic patients with stable coronary artery disease who were enrolled in the Bezafibrate Infarction Prevention Registry between February 1990 and October 1992 and followed up through December 2014. The study cohort was divided into 4 groups: patients without MetS or impaired fasting glucose (IFG), patients with IFG but without MetS, patients with MetS but without IFG, and patients with both MetS and IFG. Kaplan-Meier survival analysis showed that at 20 years of follow-up, the rates of all-cause mortality were the highest among patients with both MetS and IFG (66%). Patients with IFG without MetS experienced a significantly higher mortality rate compared with those with MetS without IFG (61% versus 56%; log-rank P<0.001). Multivariable Cox proportional hazard analysis showed that the final Cox model demonstrated that the additive effect of MetS (hazard ratio, 1.13; 95% confidence interval, 1.1-1.16; P=0.02) and IFG (hazard ratio, 1.54; 95% confidence interval, 1.46-1.62; P<0.001) on 20 years mortality was nonsignificant (hazard ratio, 1.01; 95% confidence interval, 0.93-1.11; P=0.69). IFG was associated with the most pronounced increase in mortality risk among the individual components (hazard ratio, 1.22; 95% confidence interval, 1.14-1.3; P<0.001). CONCLUSIONS: Our findings suggest that IFG alone is a major independent predictor of long-term mortality among patients with stable coronary artery disease versus other components of the MetS.

Elevated Admission Potassium Levels and 1-Year and 10-Year Mortality Among Patients With Heart Failure.

BACKGROUND: Limited, contradictory data exist regarding the effect of hyperkalemia on both short- and long-term all-cause mortality among hospitalized patients with heart failure (HF). METHODS: We analyzed 4,031 patients who were enrolled in the Heart Failure Survey in Israel. The study patients were grouped into 3 different potassium (K) categories. Multivariate analysis was used to determine the association of potassium levels as well as 1- and 10-year all-cause mortality. RESULTS: A total of 3,349 patients (83%) had K < 5mEq/L, whereas 461 patients (11%) had serum K ≥ 5mEq/L but≤ 5.5mEq/L and 221 patients (6%) had K > 5.5mEq/L. Survival analysis showed that 1-year mortality rates were significantly higher among patients with K > 5.5mEq/L (40%) and those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L (34%) compared to those with K < 5mEq/L (27%); (all log rank P < 0.01). Similarly, 10-year mortality rates among those with K > 5.5mEq/L were 92%, whereas among those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L rates were 88%, and in those with K < 5mEq/L rates were 82%; (all log rank P < 0.001). Consistently, multivariate analysis showed that compared to patients with K < 5mEq/L, patients with K > 5.5mEq/L had an independently 51% and 31% higher mortality risk at 1 year and 10 years, respectively (1-year hazard ratio = 1.51, 95% CI: 1.04-2.2; 10-years hazard ratio = 1.31, 95% CI: 1.035-1.66), whereas patients with serum K ≥ 5mEq/L but ≤ 5.5mEq/L had comparable adjusted mortality risk to patients with K < 5mEq/L at 1 and 10 years. CONCLUSIONS: Among hospitalized patients with HF, admission K > 5.5mEq/L was independently associated with increased short- and long-term mortality, whereas serum K ≥ 5mEq/L but ≤ 5.5mEq/L was not independently associated with worse outcomes.

Evaluation of Patients with Acute Chest Pain Using SPECT Myocardial Perfusion Imaging: Prognostic Implications of Mildly Abnormal Scans.

BACKGROUND: While patients presenting to emergency departments (ER) with chest pain are increasingly managed in chest pain units (CPU) that utilize accelerated diagnostic protocols for risk stratification, such as single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), data are lacking regarding the prognostic implications of mildly abnormal scans in this population. OBJECTIVES: To evaluate the prognostic implications of mildly abnormal SPECT MPI results in patients with acute chest pain. METHODS: Of the 3753 chest pain patients admitted to the CPU at the Leviev Heart Center, Sheba Medical Center 1593 were further evaluated by SPECT MPI. Scans were scored by extent and severity of stress-induced perfusion defects, with 1221 patients classified as normal, 82 with myocardial infarction without ischemia, 236 with mild ischemia, and 54 with more than mild ischemia. Mild ischemia patients were further classified to those who did and did not undergo coronary angiography within 7 days. RESULTS: Mild ischemia patients who underwent coronary angiography were more likely to be male (92% vs. 81%, P = 0.01) and to have left anterior descending ischemia (67% vs. 42%, P = 0.004). After 50 months, these patients returned less often to the ER with chest pain (53% vs. 87%, P < 0.001) and had a lower combined endpoint of acute coronary syndrome and death (8% vs. 16%, P < 0.001). CONCLUSIONS: Compared to patients with chronic stable angina, patients presenting with acute chest pain exhibiting mildly abnormal SPECT MPI findings should perhaps undergo a more aggressive diagnostic and therapeutic approach.

Endothelial function predicts 1-year adverse clinical outcome in patients hospitalized in the emergency department chest pain unit.

BACKGROUND: Endothelial function is a marker for cardiovascular risk. Thus, abnormal endothelial function may be associated with adverse 1-year outcome in patients presenting to the emergency department chest pain unit (CPU). METHODS: Following endothelial function testing, using EndoPAT 2000 in 300 consecutive subjects with chest pain and no history of coronary artery disease (CAD) presenting to CPU, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability. RESULTS: Mean 10-year Framingham risk score (FRS) was 6.6±5.9%, median reactive hyperemia index (RHI) as a measure of endothelial function 2.08 and mean was 2.0±0.4. During a 1-year follow-up, the 20 (6.6%) patients who developed major adverse cardiovascular end-points (MACE), including all-cause mortality, non-fatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions, had higher 10-year FRS (10.5±8.2% vs 6.3±5.7%; p<0.001), lower baseline RHI (1.43±0.41 vs 2.10±0.44; p<0.001) and a greater extent of coronary atherosclerosis lesions (70% vs 3.9%, p<0.001) in the CPU CCTA, compared to those without MACE. RHI≤the median was associated with higher 1-year MACE (13% vs 0.7%, p<0.001) compared to RHI>the median. Multivariate analysis demonstrated that RHI≤the median is an independent predictor of coronary atherosclerosis lesions in the CPU CCTA (OR 5.98, 95% CI 03.29-10.88; p<0.001) and 1-year MACE (OR 15.207, 95% CI 2.00-115.33; p<0.01). CONCLUSIONS: Our findings suggest that non-invasive endothelial function testing may have clinical utility in triaging patients in the CPU and in predicting 1-year MACE.

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study.

BACKGROUND: Patients with type 2 diabetes present with an accelerated atherosclerotic process. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors (gliptins) have anti-inflammatory and anti-atherosclerotic effects, yet clinical data are scarcely available. DESIGN AND METHODS: A prospective, randomized, open-label study was performed in 60 patients with coronary artery disease (CAD) and type 2 diabetes, who participated in a cardiac rehabilitation program. After a washout period of 3 weeks, patients were randomized in a 2:1 ratio to receive combined vildagliptin/metformin therapy (intervention group: n = 40) vs. metformin alone (control group: n = 20) for a total of 12 weeks. Blinded assessment of interleukin-1ß (IL-1ß, the primary endpoint), hemoglobin A1c (HbA1c), and high sensitivity C reactive protein (hsCRP), were performed at baseline and after 12 weeks. RESULTS: Mean age of study patients was 67 ± 9 years, 75% were males, and baseline HbA1c and inflammatory markers levels were similar between the two groups. At 12 weeks of follow up, levels of IL-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß among the control group, which was not observed in the intervention group (49 vs. 4%, respectively; p < 0.001). The hsCRP was lowered by 60% in the vildagliptin/metformin group vs. 23% in the metformin group (p < 0.01). Moreover, a significant relative reduction of the HbA1c was seen in the intervention group (7% reduction, p < 0.03). CONCLUSION: The addition of vildagliptin to metformin treatment in patients with type 2 diabetes and CAD led to a significant suppression of the IL-1ß elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213.

Cardiac rehabilitation following an acute coronary syndrome: Trends in referral, predictors and mortality outcome in a multicenter national registry between years 2006-2013: Report from the Working Group on Cardiac Rehabilitation, the Israeli Heart Society.

Background Utilization of cardiac rehabilitation is suboptimal. The aim of the study was to assess referral trends over the past decade, to identify predictors for referral to a cardiac rehabilitation program, and to evaluate the association with one-year mortality in a large national registry of acute coronary syndrome patients. Design and methods Data were extracted from the Acute Coronary Syndrome Israeli Survey national surveys between 2006-2013. A total of 6551 patients discharged with a diagnosis of acute coronary syndrome were included. Results Referral to cardiac rehabilitation following an acute coronary syndrome increased from 38% in 2006 to 57% in 2013 ( p for trend < 0.001). Multivariate modeling identified the following independent predictors for non-referral: 2006 survey, older age, female sex, past stroke, heart or renal failure, prior myocardial infarction, minority group, and lack of in-hospital cardiac rehabilitation center (all p < 0.01). Kaplan-Meier survival analyses showed one-year survival rates of 97% vs 92% in patients referred for cardiac rehabilitation as compared to those not referred (log-rank p < 0.01). Multivariate analysis showed that referral for cardiac rehabilitation was associated with a 27% mortality risk reduction at one-year follow-up ( p = 0.03). Consistently, a 32% lower one-year mortality risk was evident in a propensity score matched group of 3340 patients (95% confidence interval 0.48-0.95, p = 0.02). Conclusions Over the past decade there was a significant increase in cardiac rehabilitation referral following an acute coronary syndrome. However, cardiac rehabilitation is still under-utilized in important high-risk subsets of this population. Patients referred to cardiac rehabilitation have a lower adjusted mortality risk.

Feasibility and Safety of Evaluating Patients with Prior Coronary Artery Disease Using an Accelerated Diagnostic Algorithm in a Chest Pain Unit.

An accelerated diagnostic protocol for evaluating low-risk patients with acute chest pain in a cardiologist-based chest pain unit (CPU) is widely employed today. However, limited data exist regarding the feasibility of such an algorithm for patients with a history of prior coronary artery disease (CAD). The aim of the current study was to assess the feasibility and safety of evaluating patients with a history of prior CAD using an accelerated diagnostic protocol. We evaluated 1,220 consecutive patients presenting with acute chest pain and hospitalized in our CPU. Patients were stratified according to whether they had a history of prior CAD or not. The primary composite outcome was defined as a composite of readmission due to chest pain, acute coronary syndrome, coronary revascularization, or death during a 60-day follow-up period. Overall, 268 (22%) patients had a history of prior CAD. Non-invasive evaluation was performed in 1,112 (91%) patients. While patients with a history of prior CAD had more comorbidities, the two study groups were similar regarding hospitalization rates (9% vs. 13%, p = 0.08), coronary angiography (13% vs. 11%, p = 0.41), and revascularization (6.5% vs. 5.7%, p = 0.8) performed during CPU evaluation. At 60-days the primary endpoint was observed in 12 (1.6%) and 6 (3.2%) patients without and with a history of prior CAD, respectively (p = 0.836). No mortalities were recorded. To conclude, Patients with a history of prior CAD can be expeditiously and safely evaluated using an accelerated diagnostic protocol in a CPU with outcomes not differing from patients without such a history.