Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

High neutrophil-to-lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline.

BACKGROUND: Cardiotoxicity, defined mainly as left ventricle (LV) dysfunction, is a significant side effect of anthracyclines (ANT) therapy. The need for an early simple marker to identify patients at risk is crucial. A high neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in cancer patients; however, its role as a predictor for cardiotoxicity development is unknown. OBJECTIVE: Evaluating whether elevated NLR, during ANT exposure, plays a predictive role in the development of cardiotoxicity as defined by LV global longitudinal strain (LV GLS) relative reduction (≥10%). METHODS AND RESULTS: Data were prospectively collected as part of the Israel Cardio-Oncology Registry. A total of 74 female patients with breast cancer, scheduled for ANT therapy were included. NLR levels were assessed at baseline (T1) and during ANT therapy (T2). All patients underwent serial echocardiography at baseline (T1) and after the completion of ANT therapy (T3). NLR ≥ 2.58 at T2 was found to be the optimal predictive cutoff for LV GLS deterioration. A relative LV GLS reduction ≥10% was significantly more common among patients with high NLR (50% vs. 20%, p = .009). NLR ≥ 2.58 at T2 increases the risk for LV GLS reduction by fourfold (odds ratio [OR]: 4.63, 95% confidence interval [CI]: 1.29-16.5, p = .02), with each increase of 1-point NLR adding an additional 15% risk (OR: 1.15, 95% CI: 1.01-1.32, p = .046). CONCLUSIONS: Our study provides novel data that high NLR levels, during ANT exposure, have an independent association with the development of LV dysfunction. Routine surveillance of NLR may be an effective means of risk-stratifying.

Immune Checkpoint Inhibitor-Induced Myocarditis vs. COVID-19 Vaccine-Induced Myocarditis-Same or Different?

Immune checkpoint inhibitor (ICI) and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis possibly share common mechanisms secondary to overactivation of the immune system. We aimed to compare the presenting characteristics of ICIs and COVID-19 vaccine-induced myocarditis. We performed a retrospective analysis of characteristics of patients diagnosed with either ICIs or COVID-19 vaccine-induced myocarditis and compared the results to a control group of patients diagnosed with acute viral myocarditis. Eighteen patients diagnosed with ICIs (ICI group) or COVID-19 vaccine (COVID-19 vaccine group)-induced myocarditis, and 20 patients with acute viral myocarditis (Viral group) were included. The ICI group presented mainly with dyspnea vs. chest pain and fever among the COVID-19 vaccine and Viral groups. Peak median high sensitivity Troponin I was markedly lower in the ICI group (median 619 vs. 15,527 and 7388 ng/L, p = 0.004). While the median left ventricular (LV) ejection fraction was 60% among all groups, the ICI group had a lower absolute mean LV global longitudinal strain (13%) and left atrial conduit strain (17%), compared to the COVID-19 vaccine (17% and 30%) and Viral groups (18% and 37%), p = 0.016 and p = 0.001, respectively. Despite a probable similar mechanism, ICI-induced myocarditis's presenting characteristics differed from COVID-19 vaccine-induced myocarditis.

Valvular Heart Disease following Anthracycline Therapy-Is It Time to Look beyond Ejection Fraction?

The association between anthracycline (ANT) and left ventricle (LV) dysfunction is well known; however, data regarding its direct effect on cardiac valve function is limited. We aimed to evaluate how ANT therapy affected valvular function in patients diagnosed with breast cancer. Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). Patients underwent echocardiography exams at baseline (T1), during ANT therapy (T2), and after completion within 3 months (T3) and 6 months (T4). A total of 141 female patients were included, with a mean age of 51 ± 12 years. From T1 to T4, we observed a significant deterioration in LV ejection fraction (60.2 ± 1.5 to 59.2 ± 2.7%, p = 0.0004) and LV global longitudinal strain (−21.6 (−20.0−−23.0) to −20.0 (−19.1−−21.1)%, p < 0.0001)), and an increase in LV end-systolic diameter (25 (22−27) to 27 (24−30) mm, p < 0.0001). We observed a significant increase in the incidence of new mitral regurgitation (MR) development (4 to 19%, p < 0.0001), worsening with concomitant trastuzumab therapy (6% to 31%, p = 0.003), and a trend for tricuspid regurgitation development (4% to 8%, p = 0.19). ANT therapy is associated with the development of a new valvular disease, mainly MR, which may imply the need for a valvular focus in the monitoring of cancer patients.

Prevalence of Right Ventricle Strain Changes following Anthracycline Therapy.

BACKGROUND: Anthracycline (ANT) is the most recognized therapy known to cause cardiotoxicity, mainly left ventricle (LV) dysfunction. Global Longitudinal Strain (GLS) is the optimal tool for assessment of subclinical LV dysfunction. Right ventricle (RV) function has been recognized as an independent factor for cardiac outcomes; however, data evaluating RV GLS is limited. We aimed to evaluate the change in RV GLS following ANT therapy. METHODS: The study cohort is part of the Israel Cardio-Oncology Registry (ICOR). All patients performed echocardiography before (T1) and at the end (T3) of ANT therapy. A significant reduction was defined as a relative reduction of ≥10% in RV GLS values. RESULTS: The study included 40 female patients with breast cancer treated with ANT. During follow-up, both RV GLS and free wall longitudinal strain systolic peak (RV FWLS PK) decreased significantly (p < 0.001 and p = 0.002). Altogether, 30 (75%) and 23 (58%) patients showed RV GLS and RV FWLS PK ≥ 10% relative reduction. At T3, LV ejection fraction and LV GLS were within normal range. CONCLUSIONS: RV GLS and RV FWLS PK reduction following ANT exposure is extremely frequent, comparing to LV GLS reduction.

Assessment of Kidney Function After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. OBJECTIVE: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. DESIGN: This is a prospective single center study. SETTING: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. PATIENTS: The cohort included 1321 patients who underwent TAVR. MEASUREMENTS: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. METHODS: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. RESULTS: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). LIMITATIONS: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. CONCLUSIONS: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.

CONTEXTE: L'implantation transcathéter de valvule aortique (ITVA), bien qu'elle soit associée à un risque accru d'insuffisance rénale aiguë (IRA), est susceptible d'améliorer la fonction rénale. OBJECTIFS: Évaluer l'ampleur de l'amélioration de la fonction rénale (AFR) après une ITVA et évaluer son incidence sur le taux de mortalité à long terme. TYPE D'ÉTUDE: Étude prospective menée dans un seul centre hospitalier. CADRE: Le service de cardiologie, unité interventionnelle, d'un centre de soins tertiaires. SUJETS: La cohorte était constituée de 1 321 patients ayant subi une ITVA. MESURES: Le taux de créatinine sérique a été mesuré à l'inclusion, avant l'intervention et pour les 7 jours suivants, ou jusqu'au congé du patient. MÉTHODOLOGIE: L'AFR a été définie comme l'image miroir de l'IRA, soit une réduction de plus de 0,3 mg/dl du taux de créatinine après l'intervention par rapport au taux minimum de créatinine mesuré pré-ITVA, ou un rapport entre la créatinine minimale post-ITVA et la créatinine pré-ITVA inférieur à 0,66 jusqu'à 7 jours après l'intervention. Les patients ont été classés en trois groupes et comparés selon des critères cliniques en fonction de la modification de la fonction rénale après l'intervention : un groupe AFR, un groupe IRA et un groupe « fonction rénale préservée ¼ (FRP). Le critère principal était la mortalité toutes causes confondues. RÉSULTATS: L'incidence d'une AFR était de 5 % et elle s'est avérée mineure et d'importance clinique incertaine pour 55 des 66 patients concernés. La proportion de patients atteints d'IRA était de 19,1 %. Après l'analyse multivariée, un débit de filtration glomérulaire estimé (DFGe) inférieur à 60 ml/min/1,73 m2 s'est avéré un facteur prédictif de l'AFR [rapport de cotes pour une AFR : 0,93 (IC : 0,91-0,95; p < 0,001)]. Les patients du groupe AFR présentaient un score de la Society of Thoracic Surgery (STS) plus élevé que ceux des autres groupes. Le taux de mortalité était similaire pour les groupes AFR et FRP (respectivement 43,9 % et 33,8 %), mais s'est avéré significativement plus élevé dans le groupe IRA (60,7 %; p < 0,001). LIMITES: Manque de consensus autour de la définition d'une amélioration de la fonction rénale dans les différentes études.Étude menée dans un seul centre.Bien que les données aient été recueillies de façon prospective, le plan d'analyse n'a été défini qu'après la collecte des données. CONCLUSION: L'amélioration de la fonction rénale après l'ITVA n'était pas un phénomène courant dans notre cohorte et n'a pas permis de réduire le taux de mortalité global.

Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation.

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e' septal (P=0.026), higher E/e' septal (P=0.035), and a trend of E/e' average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.

COVID-19, a tale of two peaks: patients' characteristics, treatments, and clinical outcomes.

Coronavirus 2019 disease (COVID-19) continues to challenge healthcare systems globally as many countries are currently experiencing an increase in the morbidity and mortality. Compare baseline characteristics, clinical presentation, treatments, and clinical outcomes of patients admitted during the second peak to those admitted during the first peak. Retrospective analysis of 258 COVID-19 patients consecutively admitted to the Tel Aviv Medical Center, of which, 131 during the first peak (March 21-May 30, 2020) and 127 during the second peak (May 31-July 16, 2020). First and second peak patients did not differ in baseline characteristics and clinical presentation at admission. Treatment with dexamethasone, full-dose anticoagulation, tocilizumab, remdesivir, and convalescent plasma transfusion were significantly more frequent during the second peak, as well as regimens combining 3-4 COVID-19-directed drugs. Compared to the first peak, 30-day mortality and invasive mechanical ventilation rates as well as adjusted risk were significantly lower during the second peak (10.2%, vs 19.8% vs p = 0.028, adjusted HR 0.39, 95% CI 0.19-0.79, p = 0.009 and 8.8% vs 19.3%, p = 0.002, adjusted HR 0.29, 95% CI 0.13-0.64, p = 0.002; respectively). Rates of 30-day mortality and invasive mechanical ventilation, as well as adjusted risks, were lower in the second peak of the COVID-19 pandemic among hospitalized patients. The change in treatment strategy and the experienced gained during the first peak may have contributed to the improved outcomes.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

Long-term Implications of Post-Procedural Left Ventricular End-Diastolic Pressure in Patients Undergoing Transcatheter Aortic Valve Implantation.

Current risk models have only limited accuracy in predicting transcatheter aortic valve Implantation (TAVI) outcomes and there is a paucity of clinical variables to guide patient management after the procedure. The prognostic impact of elevated left ventricular end-diastolic pressure (LVEDP) in TAVI patients is unknown. The aim of the present study was to evaluate the prognostic value of after-procedural LVEDP in patients who undewent TAVI. Consecutive patients with severe symptomatic aortic stenosis who undewent TAVI were divided into 2 groups according to after-procedural LVEDP above and below or equal 12 mm Hg. Collected data included baseline clinical, laboratory and echocardiographic variables. We evaluated the impact of elevated vs. normal LVEDP on in-hospital outcomes, short- and long-term mortality. Eight hundred forty-five patients were included in the study with complete in-hospital and late mortality data available for all survivors (median follow-up 29.5 months [IQR 16.5 to 48.0]). The mean age (±SD) was 82.3±6.2 years and mean Society of Thoracic Surgery score was 4.0%±3.0%. Patients with LVEDP>12 mm Hg (n = 591, 70%) and LVEDP≤12 mm Hg (n = 254, 30%) had a 6-months mortality rate of 6.8% and 2%, respectively (P=0.004) and a 1-year mortality rate of 10.1% vs 4.9%, respectively (p = 0.017). By multivariable analysis, after-procedural LVEDP>12 mm Hg was independently associated with all-cause mortality (HR 2.45, 95% CI 1.58 to 3.76, p <0.001) during long-term follow-up. In conclusion, elevated after-procedural LVEDP in patients who undewent TAVI is an independent predictor of mortality following TAVI. Further research regarding the use of LVEDP as a tool for after-procedural medical management is warranted.

Left Atrial Strain changes in patients with breast cancer during anthracycline therapy.

BACKGROUND: Cardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for new imaging techniques for the early subclinical detection of cardiotoxic effect. We aimed to evaluate left atrial strain (LAS) changes during ANT therapy and to assess the correlation between LAS and the routine echocardiographic diastolic parameters. METHODS AND RESULTS: Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline LAS (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). LAS was assessed in 3 phases: Reservoir (LASr), Conduit (LASc) and Pump (LASp). Significant reduction in LASr was determined by either a relative reduction of >10% or an absolute value of <35%. From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 237±13.24mg/m2. At T3, significant reduction in LASr was observed among 50% of the patients with a mean LASr reduction from 40.15 ± 6.83% to 36.04 ± 7.73% (p < 0.001). LASc showed significant reduction as well (p < 0.004) as opposed to LASp (p=0.076). Both LASr and LASc showed significant correlation to the routine diastolic parameters. CONCLUSIONS: LASr and LASc reduction are frequent and occur early in the course of ANT therapy, showing significant correlation to the routine echocardiographic diastolic parameters, which may imply a role in the detection of early cardiotoxicity.

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

The impact of normal range estimated glomerular filtration rate on mortality in selected patients undergoing coronary angiography - a long-term follow-up.

BACKGROUND: Estimated glomerular filtration rate (eGFR) predicts mortality and adverse cardiovascular events in people with chronic kidney disease. The significance of eGFR within the normal range and its long-term effect on clinical adverse events is unknown. We examined the effect of normal range or mildly reduced eGFR on long-term mortality in a large prospective registry. METHODS: The study included consecutive patients undergoing clinically-driven coronary angiography who had an eGFR ≥60 ml/min/1.73 m2. Baseline clinical characteristics were assessed, and patients were followed-up for the occurrence of all-cause mortality. Cox regression analysis was used to evaluate the impact of eGFR. RESULTS: A total of 4186 patients were recruited. Median follow-up time was 2883 days (7.9 years). Mean age was 62.0 ± 11.3 years with 77.4% males. Clinical presentation included acute coronary syndrome and stable angina. In a multivariable model adjusted for possible confounding factors, decreasing eGFR within the normal and mildly reduced range was inversely associated with long-term all-cause mortality with a hazard ratio (HR) of 1.32 for every decrease of 10 ml/min/1.732 in eGFR. Compared to eGFR > 100 ml/min/1.732, there was a graded association between lower eGFR values and increased long term mortality with a HR of 1.16 (0.59-2.31) for eGFR 90-100 ml/min/1.732, HR 1.54 (0.81-2.91) for eGFR 80-90 ml/min/1.732, HR 2.62 (1.41-4.85) for eGFR 70-80 ml/min/1.732 and HR 2.93 (1.58-5.41) for eGFR 60-70 ml/min/1.732. CONCLUSION: eGFR within the normal and mildly reduced range is an independent predictor of long-term all-cause mortality in selected patients undergoing clinically driven coronary angiography.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Cancer Therapeutics-Related Cardiac Dysfunction among Patients with Active Breast Cancer: A Cardio-Oncology Registry.

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.

Diastolic strain time as predictor for systolic dysfunction among patients with active breast cancer.

BACKGROUND: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of diastolic strain time (Dst) with the routine echocardiography diastolic parameters and estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy, were included. Echocardiography, including global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity was determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. RESULTS: Among 69 patients, 67 (97.1%) were females with a mean age of 52 ± 13 years. Dst was significantly associated with the routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3. Both in a univariate and a multivariate analyses, the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (P < .04). CONCLUSIONS: Among breast cancer patients, Dst showed high correlation to the routine diastolic echocardiography parameters. Change in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Cardio-toxicity among patients with sarcoma: a cardio-oncology registry.

BACKGROUND: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group. RESULTS: Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group. CONCLUSIONS: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

Early cardio-renal interactions among apparently healthy individuals undergoing coronary CT.

BACKGROUND: Previously we found that cardiac chambers' volumes correlate with estimated glomerular filtration rate (eGFR) of hospitalized patients. Currently we aimed to demonstrate this relation among apparently healthy individuals. METHODS: Ambulatory participants who underwent electrocardiography-gated cardiac computed tomography angiography (CCTA) were included. Subjects with an eGFR<60 ml/min/1.73m2, cardiovascular risk factors, and co-morbidities or medications which may influence cardiac chambers' volumes were excluded. Chambers' sizes were obtained by automatic four chamber volumetric analysis of the CCTAs, and calcium score was assessed using the Agatston score. RESULTS: The cohort consisted of 89 apparently healthy individuals, mostly of male gender (70%), with a mean age of 51 years and a mean eGFR of 79.5 ml/min/1.73m2. A low calcium score (≤10HU) was found in 67.4%(n = 60) of the cohort. After adjustment for baseline characteristics, renal function was associated exclusively with the volume of the left atrium (LA; b-coefficient-0.15, 95%CI -0.3- -0.01, p = .041). A 15.9% (95%CI 0.3-33.9%, p = .045) increase in LA volume index (LAVI) was found among participants with eGFR of 80-90 when compared to those with eGFR>90 ml/min/1.73m2. Participants with a low calcium score showed an increase in LAVI only when eGFR was reduced from normal (>90 ml/min/1.73m2) to 70-80 ml/min/1.73m2 (and not to 80-90 ml/min/1.73m2), revealing a percentage increase of 24.7% (95%CI 5.5-47.4%, p = .011). CONCLUSIONS: Renal function is closely related to LA volume even in the absence of overt renal failure, demonstrating that minor changes in eGFR instigate an increase in volumes. Risk factors for this interaction should be identified and treated prior to the development of cardio-renal syndrome.

The association of reduced global longitudinal strain with cancer therapy-related cardiac dysfunction among patients receiving cancer therapy.

BACKGROUND: Cardiotoxicity is a leading cause of morbidity and mortality among patients receiving cancer therapy. The most commonly used definition is cancer therapy-related cardiac dysfunction (CTRCD) defined by a left ventricular ejection fraction reduction. Global longitudinal strain (GLS) has been implied to be superior in detecting early subclinical dysfunction. OBJECTIVES: Evaluate the prevalence of reduced GLS and whether it is associated with CTRCD development among patients receiving cancer therapy. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients receiving different types of cancer therapy, who were referred to the cardio-oncology clinic. Patients were divided into two groups-reduced GLS (> - 17%) vs. preserved GLS (≤ - 17%). Multivariable analyses were adjusted for a propensity score for baseline characteristics. RESULTS: Among 291 consecutive patients, 48 (16%) patients were included in the reduced GLS group. Overall, 11 (5%) patients developed CTRCD at following echocardiogram evaluation. Patients with preserved GLS had a significantly lower risk for CTRCD development [odds ratio (OR) 0.11, 95% confidence interval (CI) 0.03-0.41, p = 0.001], with every 1-unit improvement of GLS the risk of CTRCD decreased by 16% (OR 0.84, 95%CI 0.73-0.95, p = 0.007). After adjustment for baseline characteristics, including cardiovascular risk factors and systolic function, preserved GLS remained significantly associated with a lower risk for CTRCD development (OR 0.11, 95%CI 0.02-0.64, p = 0.014), with every 1-unit improvement lowering the risk by 19% (OR 0.81, 95%CI 0.67-0.98, p = 0.032). CONCLUSIONS: Reduced GLS is common among patients receiving cancer therapy and may identify patients at increased risk for CTRCD development.

Incidence, determinants and impact of acute kidney injury in patients with diabetes mellitus and multivessel disease undergoing coronary revascularization: Results from the FREEDOM trial.

BACKGROUND: The incidence and prognostic significance of acute kidney injury (AKI) in patients with diabetes mellitus and multivessel coronary artery disease undergoing coronary revascularization is not well known. The current analysis included patients randomized to PCI vs. CABG as part of the FREEDOM trial. We sought to examine the impact of AKI and its predictors in diabetic patients with multivessel coronary artery disease undergoing PCI vs. CABG. METHODS: We conducted a pre-specified subgroup analysis of the FREEDOM trial to examine the incidence, correlates and impact of AKI according to revascularization strategy. AKI predictors were identified using multivariable logistic regression and associations between AKI and outcomes were examined using Cox regression. The primary endpoint was the composite occurrence of all-cause death, stroke or myocardial infarction at 5 years of follow-up. RESULTS: KI occurred more frequently in patients following CABG (15.6%) compared with PCI (9.1%) (p < 0.001). AKI was associated with a higher risk for major cardiovascular events (MACE) at 5 years (34.6% vs. 20.5%, p < 0.001), an effect that remained large and significant irrespective of CABG (HR = 2.18 95% CI 1.44-3.31, p ≤0.001) or PCI (HR = 2.08 95% CI 1.35-3.21, p < 0.0001). There was a non-significant interaction (p-value = 0.89) between the revascularization method and AKI, supporting that AKI is a significant risk factor in both revascularization methods. CONCLUSIONS: Although risk for AKI was higher in patients undergoing CABG, the impact of AKI on MACE was substantial irrespective of revascularization strategy. Preventive strategies to identify patients at risk for AKI are warranted to mitigate the long-term effects of this complication.