Publications by authors named "Robert Klempfner"

109 Publications

Ethnic Disparity in Mortality Among Ischemic Heart Disease Patients. A-20 Years Outcome Study From Israel.

Front Cardiovasc Med 2021 30;8:661390. Epub 2021 Jun 30.

Leviev Heart Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Long-term morbidity and mortality data among ischemic heart disease (IHD) patients of different ethnicities are conflicting. We sought to determine the independent association of ethnicity and all-cause mortality over two decades of follow-up of Israeli patients. Our study comprised 15,524 patients including 958 (6%) Arab patients who had been previously enrolled in the Bezafibrate Infarction Prevention (BIP) registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for long-term mortality. We compared clinical characteristics and outcomes of Israeli Arabs and Jews. Propensity score matching (PSM) (1:2 ratios) was used for validation. Arab patients were significantly younger (56 ± 7 years vs. 60 ± 7 years; < 0.001; respectively), and had more cardiovascular disease (CVD) risk factors. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among Arab patients (67 vs. 61%; log-rank < 0.001). Multivariate adjusted analysis showed that mortality risk was 49% greater (HR 1.49; 95% CI: 1.37-1.62; < 0.001) among Arabs. Arab ethnicity is independently associated with an increased 20-year all-cause mortality among patients with established IHD.
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http://dx.doi.org/10.3389/fcvm.2021.661390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277917PMC
June 2021

Apixaban in Patients with Atrial Fibrillation and Severe Renal Dysfunction: Findings from a National Registry.

Isr Med Assoc J 2021 Jun;23(6):353-358

Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, NY, USA.

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.
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June 2021

Acute myocardial infarction in the Covid-19 era: Incidence, clinical characteristics and in-hospital outcomes-A multicenter registry.

PLoS One 2021 18;16(6):e0253524. Epub 2021 Jun 18.

Lev Leviev Heart and Vascular Center, Sheba Medical Center, Tel Hashomer, Israel.

Background: We aimed to describe the characteristics and in-hospital outcomes of ST-segment elevation myocardial infarction (STEMI) patients during the Covid-19 era.

Methods: We conducted a prospective, multicenter study involving 13 intensive cardiac care units, to evaluate consecutive STEMI patients admitted throughout an 8-week period during the Covid-19 outbreak. These patients were compared with consecutive STEMI patients admitted during the corresponding period in 2018 who had been prospectively documented in the Israeli bi-annual National Acute Coronary Syndrome Survey. The primary end-point was defined as a composite of malignant arrhythmia, congestive heart failure, and/or in-hospital mortality. Secondary outcomes included individual components of primary outcome, cardiogenic shock, mechanical complications, electrical complications, re-infarction, stroke, and pericarditis.

Results: The study cohort comprised 1466 consecutive acute MI patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with STEMI: 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. Although STEMI patients admitted during the Covid-19 period had fewer co-morbidities, they presented with a higher Killip class (p value = .03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122-292) in 2018 to 290 minutes (IQR 161-1080, p < .001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint in the multivariable regression model (OR 1.65, 95% CI 1.03-2.68, p value = .04). Furthermore, the rate of mechanical complications was four times higher during the Covid-19 era (95% CI 1.42-14.8, p-value = .02). However, in-hospital mortality remained unchanged (OR 1.73, 95% CI 0.81-3.78, p-value = .16).

Conclusions: STEMI patients admitted during the first wave of Covid-19 outbreak, experienced longer total ischemic time, which was translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events, compared with parallel period.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253524PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213163PMC
July 2021

Safety of High-Dose Dabigatran in Elderly and Younger Patients with a Low Bleeding Risk: A Prospective Observational Study.

Cardiology 2021 Jun 11:1-5. Epub 2021 Jun 11.

Cardiology Department, Rabin Medical Center, Petah-Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.

Introduction: In patients with atrial fibrillation (AF) at risk for stroke, dabigatran 150 mg twice a day (DE150) is superior to warfarin for stroke prevention. However, there is paucity of data with respect to bleeding risk at this dose in elderly patients (≥75 years). We aimed to evaluate the safety of DE150 in comparison to warfarin in a real-world population with AF and low bleeding risk (HAS-BLED score ≤2).

Methods: In this prospective observational study, 754 consecutive patients with AF and HAS-BLED score ≤2 were included. We compared outcome of elderly patients (age ≥75 tears) to younger patients (age <75 years). The primary end point was the combined incidence of all-cause mortality, stroke, systemic emboli, and major bleeding event during a mean follow-up of 1 year.

Results: There were 230 (30%) elderly patients, 151 patients were treated with warfarin, and 79 were treated with DE150. Fifty-two patients experienced the primary endpoint during the 1-year follow-up. Among the elderly, at 1-year of follow-up, the cumulative event rate of the combined endpoint in the DE150 and warfarin was 8.9 and 15.9% respectively (p = 0.14). After adjustment for age and gender, patients who were treated with DE150 had a nonsignificant difference in the risk for the combined end point as patients treated with warfarin both among the elderly and among the younger population (HR 0.58, 95% C.I = 0.25-1.39 and HR = 1.12, 95% C.I 0.62-2.00, respectively [p for age-group-by-treatment interaction = 0.83).

Conclusions: Our results suggest that Dabigatran 150 mg twice a day can be safely used among elderly AF patients with low bleeding risk.
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http://dx.doi.org/10.1159/000516368DOI Listing
June 2021

Illness perceptions of Israeli hospitalized patients with acute coronary syndrome.

Nurs Crit Care 2021 Mar 29. Epub 2021 Mar 29.

Department of Community Cardiology, Tel-Aviv Jaffa District, Clalit Health Services, Tel Aviv, Israel.

Background: Illness perceptions (IPs) can affect cardiac health behaviours and outcomes.

Aims And Objectives: To investigate IPs among patients hospitalized with acute coronary syndrome (ACS).

Design: Longitudinal survey.

Methods: The ACS Israel Study is a national, biennial registry, enrolling all patients with ACS admitted to cardiac intensive care or cardiology wards in Israel within a 2-month period. Data includes demographics, medical history, and treatment for ACS using an electronic database. In 2018, a nursing component was added, including the Brief Illness Perception Questionnaire. Data were analysed using descriptive statistics and a two-stage cluster analysis.

Results: A total of 990 subjects were surveyed. Mean age was 62.8 (SD = 12.5) and most respondents were male and married. Mean IP scores ranged from 3.28 to 6.06. Three clusters were found; one only of women and two only of men (one cluster with lower IPs and little previous medical history and cardiac risk factors and the second with higher IPs, greater medical history, and cardiac risk factors. Those with higher education scored lower on several IPs.

Conclusions: Subjects were moderately cognitively and emotionally impacted by their illness. Men tended to perceive their illness as having either a relatively strong or a relatively weak emotional and cognitive impact on their lives, where women were somewhere in-between. Participants with an academic education perceived less of an impact of the illness while those with a previous history of chronic disease reported the opposite. It is recommended that educational interventions and in-depth qualitative studies be designed that investigate the development of IPs during hospitalization to potentially improve cardiac health behaviours, especially among those without a previous medical history and cardiac risk factors.

Relevance To Clinical Practice: Those without a history of chronic disease or a lower level of education are less likely to absorb the full impact of a cardiac event while hospitalized and should, therefore, be monitored more closely and coached with greater intensity than other groups while still in-hospital.
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http://dx.doi.org/10.1111/nicc.12616DOI Listing
March 2021

Non-interventional weight changes affect systolic blood pressure in normotensive individuals.

J Clin Hypertens (Greenwich) 2021 05 6;23(5):990-998. Epub 2021 Mar 6.

Department of Internal Medicine D and Hypertension Unit, Tel-Hashomer, Israel.

The association between obesity and hypertension is well established. Weight loss has been shown to reduce blood pressure (BP) among hypertensive patients. Nevertheless, the effect of weight changes on BP in normotensive individuals is less clear. The author explored the association between non-interventional weight alterations and BP changes in a large cohort of normotensive adults. This is a retrospective analysis of normotensive individuals, between 2010 and 2018. All weight changes were non-interventional. Body mass index (BMI) and BP were measured annually. Patients were divided according to the change in BMI between visits: reduction of more than 5% ("large reduction"), between 2.5% and 5% ("moderate reduction"), reduction of <2.5% or elevation of <2.5% ("unchanged"), elevation between 2.5% and 5% ("moderate increase"), and elevation of more than 5% ("large increase"). The primary outcome was the change in systolic BP (SBP) between the visits. The final analysis included 8723 individuals. 20% of the patients reduced their BMI by at least 2.5% and 24.5% increased their BMI by more than 2.5%. "High reduction" inferred an absolute decrease of 3.6 mmHg in SBP, while "large increase" resulted in an absolute increase of 1.9 mmHg in SBP. The proportion of individuals with at least 10 mmHg decrease in SBP progressively declined according to the relative decrease in BMI, and the proportion of patients with at least 10 mmHg increase in SBP progressively increased. This effect was more pronounced in individuals with higher baseline SBP. Among normotensive adults, modest non-interventional weight changes may have significant effects on SBP.
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http://dx.doi.org/10.1111/jch.14228DOI Listing
May 2021

The liver in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Eur J Gastroenterol Hepatol 2021 Feb 26. Epub 2021 Feb 26.

Liver Diseases Center, Sheba Medical Center Sackler Faculty of Medicine, Tel-Aviv University Infectious Diseases Unit, Sheba Medical Center Department of Internal Medicine, Sheba Medical Center Geriatrics Division, Sheba Medical Center Clinical Microbiology Laboratory, Sheba Medical Center Central Virology Laboratory, Ministry of Health, Sheba Medical Center The Leviev Heart Center, Sheba Medical Center, Tel Aviv, Israel.

Background: The ongoing outbreak of COVID-19 is associated with higher levels of morbidity and mortality among patients with comorbidities, including the metabolic syndrome. Liver impairment has been reported in up to 54% of hospitalized patients with COVID-19. The impact of COVID-19 on a preexisting chronic liver disease is an actively studied area of research. The contribution of our study is towards determining the predictors of severity and the outcome of liver injury among hospitalized patients with COVID-19 infection, including patients with a preexisting liver disease and COVID-19.

Methods: This single center retrospective cohort study included all patients ≥18 years, admitted in Sheba Medical Center with confirmed COVID-19 infection. Demographic, clinical and laboratory data were obtained using the MDClone platform and rechecked after data decryption using electronic health records.

Results: Of 382 patients with COVID-19, 66.4% had increased liver biochemistry. Mild increase was observed in 76.7%. The higher level of fibrosis-4 (FIB-4) at admission was independently associated with higher mortality rate. Preexisting liver disease was detected in 15.4% patients. Most common etiology was nonalcoholic fatty liver disease (78.7%). The mortality of hospitalized patients with preexisting liver disease was 16.7% compared to 6.8% in patients without preexisting liver disease (RR = 2.792, P = 0.01). In multivariate analysis, liver disease adjusted to age and BMI was associated with mortality with high statistical significance.

Conclusions: Patients with preexisting chronic liver disease were at a higher risk of mortality. The FIB-4 level at admission was associated with worse prognosis. These findings should be reevaluated in a larger cohort of patients.
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http://dx.doi.org/10.1097/MEG.0000000000002048DOI Listing
February 2021

Adherence to Remote Cardiac Rehabilitation During the Coronavirus Pandemic: A Retrospective Cohort Analysis.

J Cardiopulm Rehabil Prev 2021 03;41(2):127-129

Cardiac Prevention and Rehabilitation Institute, Leviev Heart Center, Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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http://dx.doi.org/10.1097/HCR.0000000000000593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927901PMC
March 2021

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

Intern Emerg Med 2021 Feb 26. Epub 2021 Feb 26.

Division of Cardiology, Leviev Heart and Vascular Center, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.

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.
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http://dx.doi.org/10.1007/s11739-021-02668-1DOI Listing
February 2021

Myocardial injury in hospitalized patients with COVID-19 infection-Risk factors and outcomes.

PLoS One 2021 26;16(2):e0247800. Epub 2021 Feb 26.

Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.

Myocardial injury in hospitalized patients is associated with poor prognosis. This study aimed to evaluate risk factors for myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) and its prognostic value. We retrieved all consecutive patients who were hospitalized in internal medicine departments in a tertiary medical center from February 9th, 2020 to August 28th with a diagnosis of COVID-19. A total of 559 adult patients were hospitalized in the Sheba Medical Center with a diagnosis of COVID-19, 320 (57.24%) of whom were tested for troponin levels within 24-hours of admission, and 91 (28.44%) had elevated levels. Predictors for elevated troponin levels were age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06), female sex (OR, 3.03; 95% CI 1.54-6.25), low systolic blood pressure (OR, 5.91; 95% CI 2.42-14.44) and increased creatinine level (OR, 2.88; 95% CI 1.44-5.73). The risk for death (hazard ratio [HR] 4.32, 95% CI 2.08-8.99) and a composite outcome of invasive ventilation support and death (HR 1.96, 95% CI 1.15-3.37) was significantly higher among patients who had elevated troponin levels. In conclusion, in hospitalized patients with COVID-19, elevated troponin levels are associated with poor prognosis. Hence, troponin levels may be used as an additional tool for risk stratification and a decision guide in patients hospitalized with COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247800PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909655PMC
March 2021

Heart Team/Guidelines Discordance Is Associated With Increased Mortality: Data From a National Survey of Revascularization in Patients With Complex Coronary Artery Disease.

Circ Cardiovasc Interv 2021 01 11;14(1):e009686. Epub 2021 Jan 11.

Sackler school of Medicine, Tel-Aviv University, Israel (G.W., A.S., Y.D.B., E.R., A.A., A.F., H.V.-A., R.K., I.G., R.K.).

Background: Practice guidelines emphasize the role of the SYNTAX score (SS; Synergy Between PCI With TAXUS and Cardiac Surgery) in choosing between percutaneous coronary intervention and coronary artery bypass graft surgery in cases of complex coronary artery disease. There is paucity of data on the implementation of these recommendations in daily practice, and on the consequences of guideline discordant revascularization.

Methods: This was a retrospective analysis of a prospective national survey of consecutive real world patients undergoing coronary revascularization for complex coronary artery disease according to decisions of local heart team at each center. SS was calculated at a dedicated CoreLab, and patients were classified as heart team/guidelines agreement/discordant.

Results: Nine hundred seventy-nine patients (571 percutaneous coronary intervention and 408 coronary artery bypass graft) were included. Mean age was 65 years and the mean SS was 22. Heart team/guidelines discordance occurred in 170 (17.3%) patients. Independent predictors of heart team/guidelines discordance were age, admission to a center with no cardiac surgery service, SS, and previous percutaneous coronary intervention/myocardial infarction. A multivariate model based on these characteristics had a C statistic of 0.83. Thirty-day outcomes were similar in the agreement/discordance groups, however, heart team/guidelines discordance was associated with a significant increase in 3 year mortality (17.6% versus 8.4%; hazard ratio, 2.05; =0.002) after multivariate adjustment.

Conclusions: Heart team/guidelines discordance is not infrequent in real world patients with complex coronary artery disease undergoing revascularization. This is more likely to occur in elderly patients, those with more complex coronary disease (as determined by the SS), and those treated at centers with no cardiac surgery service. These patients have a higher risk for mid-term mortality.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009686DOI Listing
January 2021

Comparison of Outcomes with or without Beta-Blocker Therapy After Acute Myocardial Infarction in Patients Without Heart Failure or Left Ventricular Systolic Dysfunction (from the Acute Coronary Syndromes Israeli Survey [ACSIS]).

Am J Cardiol 2021 03 12;143:1-6. Epub 2021 Jan 12.

Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.

The contemporary benefit of routine beta-blocker therapy following myocardial infraction in the absence of heart failure or left ventricular systolic dysfunction is unclear. We investigated the impact of beta-blockers on post myocardial infarction outcome in patients without heart failure or left ventricular systolic dysfunction among patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys. MACE rates at 30 days and overall mortality at one year were compared among patients discharged on beta-blockers versus not, after multivariate analysis to adjust for baseline differences. Between the years 2000 to 2016, data from 15.211consecutive ACS patients were collected. Of 7,392 patients who met the inclusion criteria, 6007 (79.9%) were discharged on beta-blocker therapy. Prescription of beta-blockers at discharge increased modestly from 32% to 38% over the 16-year period. The 30-day MACE rates were similar in patients on vs. not on beta-blockers at discharge (9.0% and 9.5%, respectively). One year survival did not differ significantly between those on vs. not on beta-blockers (HR 0.8, 95% CI 0.58 to 1.11, p = 0.18).In conclusion, beta-blocker therapy did not affect 30 days MACE or 1-year survival after myocardial infarction in patients without heart failure or reduced ejection fraction.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.044DOI Listing
March 2021

Weight gain post-heart transplantation is associated with an increased risk for allograft vasculopathy and rejection.

Clin Transplant 2021 03 19;35(3):e14187. Epub 2020 Dec 19.

Heart Transplantation Unit, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Tel Hashomer, Israel.

Objective: Obesity and overweight are associated with an increased risk for cardiovascular disease. Since fat mass (FM) and fat-free mass (FFM) both contribute to total body weight (TBW), we characterized the post-heart transplantation (HT) change in TBW and its implications for outcomes.

Methods: Post-HT changes in TBW, FM, and FFM were reviewed for 211 HT patients assessed during 1997-2017. Endpoints included cardiac allograft vasculopathy (CAV) and rejection.

Results: Median TBW increased by 7.3% at 1 year, with a significant rise in the obese category (28% vs. 13%, p < 0.001) and with FM versus FFM making the main contribution (23% vs. 3%, p < 0.001). When patients were divided according to median TBW change ("high" vs. "low"), Kaplan-Meier analysis showed that 10-year freedom from CAV (log-rank p < 0.005) and rejection (log-rank p < 0.01) was significantly higher for the "low" TBW change group. Consistently, multivariable analyses showed that the "high" group was independently associated with significant 3.5-fold and 4.2-fold increased risks for CAV (95% CI 1.4-8.7, p = 0.01) and rejection (95% CI 1.2-15.4, p = 0.03), respectively.

Conclusions: Weight gain, contributed mostly by FM, is independently associated with an increased risk for CAV and rejection. Follow-up emphasis should be placed on weight gain and preventative measures.
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http://dx.doi.org/10.1111/ctr.14187DOI Listing
March 2021

Risk factors and mortality in patients with pneumonia and elevated troponin levels.

Sci Rep 2020 12 10;10(1):21619. Epub 2020 Dec 10.

Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Pneumonia in hospitalized patients is associated with myocardial injury. In this study, we evaluated risk factors for myocardial injury in hospitalized patients with pneumonia and its prognostic value. We retrieved all patients who were hospitalized in internal medicine departments in a tertiary medical center between 2008 and 2019 with a diagnosis of pneumonia. From 2008 to 2019 a total of 20,683 adult patients were hospitalized in internal medicine wards in the Sheba Medical Center with a diagnosis of pneumonia, 8195 were tested for troponin levels, and 3207 had elevated levels. Risk factors for elevated troponin levels were age, prior diagnosis of ischemic heart disease, and elevated creatinine level upon admission. The in-hospital mortality and 1-year mortality rate were higher among patients who had elevated troponin levels when using a propensity score-based matched analysis. In conclusion, in hospitalized patients with pneumonia elevated troponin levels have a major impact on prognosis. Hence, troponin levels may be used as another tool of risk stratification for patients hospitalized with pneumonia.
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http://dx.doi.org/10.1038/s41598-020-78287-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729902PMC
December 2020

Female gender is associated with a worse prognosis amongst patients hospitalised for de-novo acute heart failure.

Int J Clin Pract 2021 Apr 26;75(4):e13902. Epub 2020 Dec 26.

The Leviev Heart Center, Sheba Medical Center, Tel-Hashomer and The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Recent evidence showed that new-onset (de-novo) acute heart failure (AHF) is a distinct type of AHF. However, the prognostic implication of gender on these patients remains unclear.

Aims: We aimed to investigate the impact of gender on both short and long-term mortality outcomes after hospitalisation for de-novo AHF.

Methods: We analysed the data of 721 patients with de-novo AHF, who were enrolled in the HF survey in Israel between March and April 2003 and were followed until December 2014.

Results: Fifty-four percent (N = 387) of the patients were men. In comparison to women, men patients were more likely to be younger, smokers, and with ischemic HF aetiology. At 30 days, mortality rates were higher in women (12% vs 7%, P = .013). Survival analysis showed that at 1 and 10 years the all-cause mortality rates were significantly higher in women (28% vs 17%, and 78% vs 67%, 1 and 10 years, P < .001, respectively). Consistently, multivariable analysis showed that women had an independently 82% and 24% higher mortality risk at 1 and 10 years, respectively, (1-year hazard ratio = 1.82; 95% confidence interval = 1.07 to 3.11, P = .03; 10-year hazard ratio = 1.24; 95% confidence interval = 1.03 to 1.48, P = .02).

Conclusions: Amongst patients with de-novo AHF, women had higher mortality rates compared with men. The observed gender-related differences in de-novo AHF patients highlight the need for further and deeper research in this field.
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http://dx.doi.org/10.1111/ijcp.13902DOI Listing
April 2021

Congestive heart failure treated with peritoneal dialysis or hemodialysis: Typical patient profile and outcomes in real-world setting.

Int J Clin Pract 2021 Mar 1;75(3):e13727. Epub 2020 Nov 1.

Institute of Nephrology and Hypertension, Sheba Medical Center and Sackler Faculty of Medicine, Tel-Hashomer, Israel.

Background: Peritoneal dialysis (PD) is increasingly used for the long-term management of hypervolemic refractory congestive heart failure (CHF) patients, in particular when complicated by renal insufficiency. While PD has many advantages over hemodialysis (HD) in those patients, there is a controversy concerning survival superiority of PD compared with HD in this population. The aim of the study was to define typical patient profile and to compare outcomes of patients with CHF and renal failure treated with HD or PD.

Methods: This retrospective cohort study enrolled CHF patients treated with chronic PD or HD between the years 2009-2018. Information at dialysis initiation included age, gender, body weight, blood pressure, cause of renal disease, comorbidities, hospitalisations, echocardiographic and laboratory parameters. Survival was compared between PD and HD patients using a Kaplan-Meier model and Cox regression analysis.

Results: CHF patients treated with PD had significantly higher eGFR and lower systolic blood pressure compared with HD treated patients. Median survival time was 13.32 (7.08, 23.28) months in the PD group and 19.68 (9.48, 39.24) months in the HD group, P = .013. After adjustment for confounders the mortality risk amongst PD and HD patients was not significantly different: adjusted HR for death in PD vs HD patients was 1.44, P = .35 for 1- year and 1.69, P = .10 for 2-year mortality. Number of hospitalisations was similar in both groups.

Conclusions: CHF patient profile was different in PD and HD. Two modalities were equally effective in the treatment of patients with CHF and renal failure considering different patient characteristics.
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http://dx.doi.org/10.1111/ijcp.13727DOI Listing
March 2021

Donor thyroid hormone therapy and heart transplantation outcomes: ISHLT transplant registry analysis.

J Heart Lung Transplant 2020 10 21;39(10):1070-1078. Epub 2020 Jun 21.

Division of Cardiovascular Medicine, University of Utah, Salt Lake City, Utah.

Background: Donor thyroid hormone (TH) supplementation therapy is widely used. Recent reports suggested an increased risk of graft dysfunction in heart transplant (HTx) recipients not receiving TH supplementation. Our aim was to determine the effect of a donor TH supplementation in a large contemporary HTx cohort.

Methods: We analyzed data reported to the International Society for Heart and Lung Transplantation Registry on adult HTx recipients transplanted from 2006 to 2016. Early graft loss (EGL) was defined as death or retransplant because of graft failure within 48 hours of transplant. Logistic regression and propensity score analyses were performed.

Results: There were 23,002 adult HTx recipients transplanted during the study period for whom data on the use of donor TH supplementation were provided to the Registry. There were 15,821 recipients whose donors had received TH supplementation, and 7,181 who had not. Multivariable analysis showed donor TH therapy to be associated with an increased risk for EGL (odds ratio, 1.51; 95% CI, 1.13-2.06; p < 0.001). Long-term survival was similar, irrespective of donor TH supplementation. Recipients whose donors had received TH supplementation exhibited a lower 8-year incidence of vasculopathy (hazard ratio, 0.90; 95% CI, 0.85-0.97; p = 0.003). These results remained consistent in a propensity-matched analysis.

Conclusions: Donor TH therapy is independently associated with an increased risk of EGL. Whether this is a result of the donor allograft intrinsic characteristics related to the reasons why TH was used or whether this is a result of a TH withdrawal effect, which could be mitigated by administration of TH to the recipient, should be further studied.
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http://dx.doi.org/10.1016/j.healun.2020.06.005DOI Listing
October 2020

High fitness might be associated with the development of new-onset atrial fibrillation in obese non-athletic adults.

Int J Clin Pract 2020 Dec 17;74(12):e13638. Epub 2020 Aug 17.

Chaim Sheba Medical Center, affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Hashomer, Israel.

Background: Data on the association between AF and fitness are conflicting.

Objectives: The aim of this analysis was to investigate the association between fitness, obesity and incidence of atrial fibrillation (AF) among apparently healthy non-athlete adults.

Methods: We investigated 20 410 self-referred subjects who were annually screened in a tertiary medical centre. All subjects were free of AF and completed maximal exercise stress test according to the Bruce protocol at baseline. Fitness was categorised into age- and sex-specific quintiles (Q) according to the treadmill time. Subjects were categorised to low (Q1-Q2) and high fitness (Q3-5) groups. The primary end point was new-onset AF during follow-up.

Results: Mean age was 48 ± 10 years and 72% were men. A total of 463 (2.3%) events occurred during an average follow-up of 8 ± 5 years corresponding to an AF event rate of 0.3% per person year. Univariate and multivariate models showed that AF risk was similar in both fitness groups. However, AF event rate was 0.55% per person year among high fitness obese subjects, compared with 0.31% for low fitness obese subjects (P < .01). Subgroup interaction analysis showed that AF risk is obesity-dependent, such that in the obese group (≥30 kg/m ) high fitness was independently associated with a significant 79% increased AF risk (95% CI 1.15-2.78; P = .01), whereas among non-obese subjects the rate of events was similar between both fitness groups (P for interaction = (.02)).

Conclusions: Our findings suggest that high fitness might be associated with increased AF risk among obese subjects.
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http://dx.doi.org/10.1111/ijcp.13638DOI Listing
December 2020

Midterm outcomes of patients with multivessel disease treated at centers with and without on-site cardiac surgery services.

J Thorac Cardiovasc Surg 2020 May 30. Epub 2020 May 30.

Department of Cardiology, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: The last decade has witnessed an increased number of stand-alone interventional cardiology units due to the consolidation of cardiac surgery services. We aimed to explore the impact of a heart team on the midterm outcomes of patients with multivessel coronary artery disease.

Methods: This prospective registry included 1063 consecutive patients with multivessel disease enrolled between January and April 2013 from all 22 hospitals in Israel that perform coronary angiography and percutaneous coronary intervention, with or without on-site cardiac surgery services.

Results: Of the 1063 patients, 576 (54%) and 487 (46%) were admitted to centers with or without on-site cardiac surgery services, respectively. Centers with cardiac surgery services compared with those without had more male patients (82% vs 77%, P = .026) and more patients who were taking aspirin (75% vs 67%, P = .008) before admission. Other characteristics were similar between the groups, including mean SYNTAX score (22.5 ± 9.6 vs 22.2 ± 10, P = .680). Late outcomes revealed a higher 6-year survival probability in centers with on-site cardiac surgery services (85.1% vs 81.3%, P = .047). Although coronary artery bypass grafting (vs percutaneous coronary intervention) was associated with a survival advantage among patients from hospitals with cardiac surgery services (89.9% vs 81.5%, P = .004), in the absence of on-site cardiac surgery services there were no differences between the 2 revascularization approaches (81.8% vs 81.1%, P = .9).

Conclusions: Patients with multivessel coronary artery disease treated in centers without on-site cardiac surgery services receive a lower rate of appropriate guideline-based intervention with coronary artery bypass grafting, which is associated with less favorable outcomes. These findings suggest that a heart-team approach should be mandatory even in centers with stand-alone interventional cardiology units.
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http://dx.doi.org/10.1016/j.jtcvs.2020.04.170DOI Listing
May 2020

Cardiorespiratory fitness and survival following cancer diagnosis.

Eur J Prev Cardiol 2020 Jul 19:2047487320930873. Epub 2020 Jul 19.

Sackler School of Medicine, Tel-Aviv University, Israel.

Aims: Data on the association of cardiorespiratory fitness with survival of cancer patients are limited. This study aimed to evaluate the association between midlife cardiorespiratory fitness and survival after a subsequent cancer diagnosis.

Methods: We evaluated 19,134 asymptomatic self-referred adults who were screened in preventive healthcare settings. All subjects were free of cardiovascular disease and cancer at baseline and completed a maximal exercise stress test. Fitness was categorised into age-specific and sex-specific quintiles according to the treadmill time and dichotomised to low (quintiles 1-2) and high fitness groups.

Results: The mean age was 50 ± 8 years and 72% were men. During a median follow-up of 13 years (interquartile range 7-16) 517 (3%) died. Overall, 1455 (7.6%) subjects developed cancer with a median time to cancer diagnosis of 6.4 years (interquartile range 3-10). Death from the time of cancer diagnosis was significantly lower among the high fitness group ( = 0.03). Time-dependent analysis showed that subjects who developed cancer during follow-up were more likely to die ( < 0.001). The association of cancer with survival was fitness dependent such that in the lower fitness group cancer was associated with a higher risk of death, whereas among the high fitness group the risk of death was lower (hazard ratio 20 vs. 15;  = 0.047). The effect modification persisted after applying a 4-year blanking period between fitness assessment and cancer diagnosis ( = 0.003).

Conclusion: Higher midlife cardiorespiratory fitness is associated with better survival among cancer patients. Our findings support fitness assessment in preventive healthcare settings.
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http://dx.doi.org/10.1177/2047487320930873DOI Listing
July 2020

Sex Differences in Clinical Characteristics and 1- and 10-Year Mortality Among Patients Hospitalized With Acute Heart Failure.

Am J Med Sci 2020 10 27;360(4):392-401. Epub 2020 May 27.

The Leviev Heart Center, Sheba Medical Center, Tel Hashomer and Sakler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: The impact of sex on mortality in patients with acute heart failure (AHF) is unresolved. We aimed to investigate the impact of sex on both short- and long-term mortality outcomes after hospitalization for AHF.

Methods: We analyzed data of 2,328 patients with AHF who were enrolled in the multicenter national survey in Israel between March and April 2003 and followed up until December 2014.

Results: Women comprised 45% of the study population. In comparison with men, women were older, had higher rates of heart failure with preserved ejection fraction as well as hypertensive heart disease and had a lower rate of coronary artery disease (all P < 0.001). Survival analysis showed that at 1 year the rate of all-cause mortality was 31% among women compared to 28% among men (P = 0.19). At 10-year follow-up mortality rates were significantly higher among women compared to men (87% vs. 83%, P = 0.048). However, this sex association disappeared once multivariable analysis was carried out, (hazard ratio [HR] = 0.93; CI = 0.79-1.09, P = 0.36). Renal dysfunction, older age and severe heart failure were consistent independent predictors of mortality among men and women. Hyponatremia was a prognostic predictor only among men, whereas digoxin use predicted mortality only among women.

Conclusions: There are important differences in the clinical characteristics between women and men hospitalized with AHF. There were no significant differences in both short- and long-term mortality following multivariable analysis. Although, most independent predictors of mortality were consistent among both sexes, few sex-based differences in prognostic predictors were identified.
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http://dx.doi.org/10.1016/j.amjms.2020.05.028DOI Listing
October 2020

[FROM 'REMOTE CARDIAC REHABILITATION' TO CHRONIC DISEASE MANAGEMENT PROGRAMS BY DIGITAL MEANS - REVIEW OF THE NATIONAL PROGRAM AS A MODEL FOR MULTI-DISCIPLINARY DISEASE MANAGEMENT].

Harefuah 2020 Jun;159(6):398-405

The Department of Health Systems Management, Faculty of Health Sciences, Ariel University, Ariel, Israel.

Introduction: Cardiovascular diseases, often accompanied by many background diseases, are the main cause of morbidity and mortality globally. Cardiac rehabilitation programs are a key component of secondary prevention and lack of participation or adherence lead to significantly higher adverse event rates including hospitalization and mortality. Technological means have great potential for improving health care outcomes. Home-cardiac rehabilitation (H-CR) using technology implements the 'patient-centered' approach within the health services. Last year, the Israeli Ministry of Health approved the H-CR program for a low-risk patient and included it into medical coverage of the state. In accordance with the Ministry of Health circular, the H-CR program is implemented at the Sheba Medical Center since November 2018. The program incorporates innovative technology alongside multi-professional care. Implementation of the program enables studies about the methods to put into effect the therapeutic model in other chronic disease management, including home rehabilitation or hospitalization programs, while maintaining patient safety and securing medical information. The purpose of this article is to review the first H-CR program in Israel, its components, benefits, and challenges, as well as, to present the therapeutic model, its competence in multidisciplinary disease management and increased responsiveness to the treatment.
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June 2020

Feasibility, Safety, and Effectiveness of a Mobile Application in Cardiac Rehabilitation.

Isr Med Assoc J 2020 06;22(6):357-363

Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Tel Hashomer, Israel.

Background: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community.

Objectives: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention.

Methods: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients.

Results: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week.

Conclusions: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.
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June 2020

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

J Cardiol 2020 10 10;76(4):335-341. Epub 2020 Jun 10.

Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel and Tel Aviv University, Israel.

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.
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http://dx.doi.org/10.1016/j.jjcc.2020.05.016DOI Listing
October 2020

Type 2 diabetes mellitus increases the mortality risk after acute coronary syndrome treated with coronary artery bypass surgery.

Cardiovasc Diabetol 2020 06 13;19(1):86. Epub 2020 Jun 13.

Department of Cardiac Surgery, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, 52621, Tel Hashomer, Israel.

Background: Type 2 diabetes mellitus (DM) is a risk factor for cardiovascular diseases and is common among patients undergoing coronary artery bypass grafting (CABG) surgery. The main objective of our study was to investigate the impact of DM type 2, and its treatment subgroups, on short- and long-term mortality in patients with acute coronary syndrome (ACS) who undergo CABG.

Methods: The study included 1307 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 527 (40%) patients were with and 780 (60%) were without DM.

Results: Compared with the non-diabetic group, the diabetic group of patients comprised more women and had more comorbidities such as hypertension, dyslipidemia, renal impairment, peripheral vascular disease and prior ischemic heart disease. Overall 30-day mortality rate was similar between DM and non-DM patients (4.2% vs. 4%, p = 0.976). Ten-year mortality rate was higher in DM compared with non-diabetic patients (26.6% vs. 17.7%, log-rank p < 0.001), and higher in the subgroup of insulin-treated patients compared to non-insulin treated patients (31.5% vs. 25.6%, log-rank p = 0.019). Multivariable analysis showed that DM increased the mortality hazard by 1.61-fold, and insulin treatment among the diabetic patients increased the mortality hazard by 1.57-fold.

Conclusions: While type 2 DM did not influence the in-hospital mortality hazard, we showed that the presence of DM among patients with ACS referred to CABG, is a powerful risk factor for long-term mortality, especially when insulin was included in the diabetic treatment strategy.
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http://dx.doi.org/10.1186/s12933-020-01069-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293781PMC
June 2020

Ethnic Differences Among Acute Coronary Syndrome Patients in Israel.

Cardiovasc Revasc Med 2020 11 23;21(11):1431-1435. Epub 2020 Apr 23.

Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

Aims: Life expectancy has increased in Israel during recent decades. However, compared to the majority, mostly Jewish population, life expectancy remains low among Israeli Arabs minority, and cardiovascular diseases are the leading cause of death. We compared baseline characteristics and outcomes between Israeli Arab and non-Arab patients hospitalized with acute coronary syndrome (ACS).

Methods And Results: A national survey accessed data of 7055 patients (1251, 18% Arabs) hospitalized with ACS. Compared to non-Arab, Arab patients were younger at ACS presentation (59 ± 11 vs. 65 ± 12 years, p < 0.01), more likely male (81% vs. 77%, p = 0.01), and with higher prevalence of diabetes mellitus (47% vs. 34%, p < 0.01) and smoking history (57% vs. 34%, p < 0.001). Among patients with ST-elevation myocardial infarction (STEMI) ACS, the mean time from first medical contact to the hospital was similar for Arab and non-Arab patients (133 and 137 min, respectively). After adjustment for age, gender, time from first medical contact to hospital arrival, diabetes, hypertension and renal failure, 1-year survival was lower among Arab patients (93.4% vs. 95.1%, p = 0.027), and 5-year survival was not statistically different (84.0% vs. 86.8%, p = 0.059). The survival differences were mostly derived from reduced survival at 1 and 5 years of STEMI Arab patients.

Conclusions: Israeli Arabs present with ACS at a younger age than non-Arabs and have higher prevalence of smoking and diabetes at presentation. Adjusted 1-year survival was lower among Arab patients. Access to medical care and in-hospital practices during ACS were similar for Arabs and non-Arabs. The findings highlight the impact of risk factors on the early presentation of ACS and the need for a robust risk reduction program for Israeli Arabs.
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http://dx.doi.org/10.1016/j.carrev.2020.04.023DOI Listing
November 2020

Cardiorespiratory Fitness Is an Independent Predictor of Cardiovascular Morbidity and Mortality and Improves Accuracy of Prediction Models.

Can J Cardiol 2021 02 16;37(2):241-250. Epub 2020 May 16.

Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address:

Background: Although cardiorespiratory fitness (CRF) is a strong independent predictor of adverse cardiovascular outcomes, it is not considered as a risk enhancer by current guidelines.

Methods: We evaluated asymptomatic self-referred adults aged 40 to 79 years of age, free of cardiovascular disease at baseline, who were screened annually and completed baseline exercise stress test. Baseline CRF was dichotomized into 2 groups: low (metabolic equivalents < 8) and high. The primary endpoint was the composite of death, nonfatal acute coronary syndrome, and stroke after excluding subjects diagnosed with metastatic cancer during follow-up.

Results: Study population included 15,445 subjects with median age of 49 years (interquartile range: 44-55). During median follow-up of 8 years 1362 (9%) subjects developed the study endpoint. Kaplan-Meier survival analysis showed that both fitness and atherosclerotic cardiovascular disease (ASCVD) were associated with developing of the study endpoint (P < 0.001 for both). Cox regression model with adjustment for ASCVD risk consistently showed that lower fitness was associated with a significant 23% higher risk to develop the study endpoint (P = 0.001). Continuous net reclassification improvement analysis showed an overall improvement of 11.4% (95% confidence interval, 8%-14.6%; P value < 0.001) in the accuracy of classification when fitness was added to the ASCVD model.

Conclusions: Low CRF is a strong independent predictor of the cardiovascular morbidity and mortality in asymptomatic adults. Addition of fitness to the pooled cohort ASCVD risk significantly improves the accuracy of the model.
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http://dx.doi.org/10.1016/j.cjca.2020.05.017DOI Listing
February 2021

Relation of Low Serum Magnesium to Mortality and Cardiac Allograft Vasculopathy Following Heart Transplantation.

Am J Cardiol 2020 05 5;125(10):1517-1523. Epub 2020 Mar 5.

Heart Transplantation Unit, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler School of Medicine, Tel Aviv University, Israel. Electronic address:

Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.
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http://dx.doi.org/10.1016/j.amjcard.2020.02.030DOI Listing
May 2020

Preoperative Statin Therapy and Heart Transplantation Outcomes.

Ann Thorac Surg 2020 10 7;110(4):1280-1285. Epub 2020 Mar 7.

Heart Transplantation Unit, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality after heart transplantation (HT). Statins are known to have immunomodulatory and antiinflammatory effects, and perioperative statin therapy has been associated with reduced cardiovascular complications and improved outcomes after cardiac and noncardiac surgery. Thus, we investigated the influence on PGD of statin therapy administered to recipients before HT.

Methods: A retrospective cohort study was conducted on 275 HT recipients assessed from 1997 to 2017; 167 (61%) had received statins during the month prior to and at time of transplantation, whereas 108 (39%) had not. Endpoints included PGD (defined according to the International Society of Heart and Lung Transplantation consensus statement), in-hospital mortality, and 1-year and 5-year survival.

Results: PGD incidence was significantly lower for statin-treated patients (21 vs 60%, P < .001). Multivariable analysis demonstrated that pre-HT statin therapy was independently associated with a significant 65% reduced risk for PGD and a 73% reduced risk for in-hospital mortality. One- and five-year mortality, adjusted for age, sex, and amiodarone therapy, were significantly lower for recipients treated with statins (hazard ratio 0.33 and 0.39, 95% confidence interval 0.17-0.63 and 0.22-0.68, respectively; P = .001).

Conclusions: Pre-HT statin therapy was independently associated with a reduced risk for PGD and mortality. Our results also suggested that statins have a beneficial prognostic impact on heart failure patients awaiting HT.
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http://dx.doi.org/10.1016/j.athoracsur.2020.02.005DOI Listing
October 2020

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.

J Am Heart Assoc 2019 12 16;8(24):e014540. Epub 2019 Dec 16.

Cardiac Rehabilitation Center Mayo Clinic Rochester MN.

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 [=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).
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http://dx.doi.org/10.1161/JAHA.119.014540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951049PMC
December 2019
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