Joseph R. Carver

Bio: Joseph R. Carver is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Cardiotoxicity & Cancer. The author has an hindex of 30, co-authored 90 publications receiving 6769 citations. Previous affiliations of Joseph R. Carver include Brown University & Cardiovascular Institute of the South.

Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Abstract: Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncologic therapeutic armamentarium. Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction. Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ven- tricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and spe- cific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat ma- lignancies, the invasive nature of the procedure, and the remarkable progress made in noninvasive cardiac imaging. The noninvasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially car- diotoxic cancer treatment.

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Abstract: ### A. Definition, classification, and mechanisms of toxicity Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncological therapeutic armamentarium.1 Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction.2 Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ventricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and specific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat malignancies, the invasive nature of the procedure, and the remarkable progress made in non-invasive cardiac imaging. The non-invasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially cardiotoxic cancer treatment.3–5 The timing of LV dysfunction can vary among agents. In the case of anthracyclines, the damage occurs immediately after the exposure;6 for others, the time frame between drug administration and detectable cardiac dysfunction appears to be more variable. Nevertheless, the heart has significant cardiac reserve, and the expression of damage in the form of alterations in systolic or diastolic parameters may not be overt until a substantial amount of cardiac reserve has been exhausted. Thus, cardiac damage may not become apparent until years or even decades after receiving the cardiotoxic treatment. This is particularly applicable to …

Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American society of clinical oncology clinical practice guideline

Abstract: Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects

Abstract: Purpose To review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors. Methods An American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006. Results Few studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans. Conclusion An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.

Assessment of Echocardiography and Biomarkers for the Extended Prediction of Cardiotoxicity in Patients Treated With Anthracyclines, Taxanes, and Trastuzumab

Abstract: Background— Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Methods and Results— Eighty-one women with newly diagnosed human epidermal growth factor receptor 2–positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro–B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P <0.0001) over 15 months. Twenty-six patients (32%, [22%–43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%–14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro–B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. Conclusions— In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

General Cardiovascular Risk Profile for Use in Primary Care The Framingham Heart Study

Abstract: Background—Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. Methods and Results—We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions (“general CVD” algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non–laboratory-based predictors. Conclusions—A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care. (Circulation. 2008;117: 743-753.)

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

2016 European Guidelines on cardiovascular disease prevention in clinical practice

Abstract: ABI : ankle–brachial (blood pressure) index ABPM : ambulatory blood pressure monitoring ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE-I : angiotensin-converting enzyme inhibitor ACS : acute coronary syndromes ADVANCE : Action in Diabetes and Vascular disease: PreterAx

2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.

Abstract: 99mTc : technetium-99m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m. : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19*2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infarction DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infarctus DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration (USA) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicorandil in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical, Angioplasty, or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction MET : metabolic equivalents MI : myocardial infarction MICRO-HOPE : Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second Randomized Intervention Treatment of Angina ROOBY : Veterans Affairs Randomized On/Off Bypass SAPT : single antiplatelet therapy SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infarction TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing Guidelines summarize and evaluate all evidence available, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well …