Immune checkpoint inhibitor-induced cardiotoxicity in patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer may precipitate cardiotoxic events. We aimed to perform a meta-analysis to evaluate the cardiotoxicity associated with ICIs in patients with lung cancer. METHODS: A literature search was conducted across four electronic databases (Cochrane CENTRAL, MEDLINE, OVID EMBASE and Google Scholar) from inception through 31st May 2023. Randomized controlled trials (RCTs) assessing the impact of ICIs on cardiac outcomes in lung cancer patients were considered for inclusion. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled and analysis was performed using a random-effects model. The Grading of Recommendations Assessment, Development and Evaluation approach was followed to assess confidence in the estimates of effect (i.e., the quality of evidence). RESULTS: A total of 30 studies including 16,331 patients, were included in the analysis. Pooled results showed that single ICI (RR: 2.15; 95% CI: 1.13-4.12; p = 0.02; I2 = 0%) or a combination of single ICI plus chemotherapy (RR: 1.38 [1.05-1.82]; p = 0.02) significantly increased the risk of cardiac adverse events when compared with chemotherapy alone. No significant difference was noted when a dual ICI (RR: 0.48 [0.13-1.80]; p = 0.27) was compared with single ICI. In addition, there was no significant association between the use of ICIs and incidence of cardiac failure (RR: 1.11 [0.48-2.58]; p = 0.80), or arrhythmia (RR: 1.87; [0.69-5.08]; p = 0.22). CONCLUSION: Compared with chemotherapy alone, use of a single ICI or a combination of single ICI plus chemotherapy significantly increased the risk of cardiotoxicity. However, employing dual immunotherapy did not result in a significant increase in the risk of cardiotoxicity when compared to the use of a single ICI.

Effectiveness of exercise modalities on breast cancer patient outcomes: a systematic review and meta-analysis.

BACKGROUND: The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a meta-analysis to assess the benefits of varying types of exercises in patients with BC. METHODS: Literature search was conducted across five electronic databases (MEDLINE, Web of Science, Scopus, Google Scholar and Cochrane) from 1st January 2000 through 19th January 2024. Randomized controlled trials (RCTs) assessing the impact of different types of exercise on outcomes related to fitness and quality of life (QOL) in patients with BC were considered for inclusion. Outcomes of interest included cardiorespiratory fitness (CRF), health-related quality of life (HRQOL), muscle strength, fatigue and physical function. Evaluations were reported as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random effects model. A p value < 0.05 was considered significant. RESULTS: Thirty-one relevant articles were included in the final analysis. Exercise intervention did not significantly improved the CRF in patients with BC when compared with control according to treadmill ergometer scale (MD: 4.96; 95%Cl [-2.79, 12.70]; P = 0.21), however exercise significantly improved CRF according to cycle ergometer scales (MD 2.07; 95% Cl [1.03, 3.11]; P = 0.0001). Physical function was significantly improved as well in exercise group reported by 6-MWT scale (MD 80.72; 95% Cl [55.67, 105.77]; P < 0.00001). However, exercise did not significantly improve muscle strength assessed using the hand grip dynamometer (MD 0.55; 95% CI [-1.61, 2.71]; P = 0.62), and fatigue assessed using the MFI-20 (MD -0.09; 95% CI [-5.92, 5.74]; P = 0.98) and Revised Piper scales (MD -0.26; 95% CI [-1.06, 0.55] P = 0.53). Interestingly, exercise was found to improve HRQOL when assessed using the FACT-B scale (MD 8.57; 95% CI [4.53, 12.61]; P < 0.0001) but no significant improvements were noted with the EORTIC QLQ-C30 scale (MD 1.98; 95% CI [-1.43, 5.40]; P = 0.25). CONCLUSION: Overall exercise significantly improves the HRQOL, CRF and physical function in patients with BC. HRQOL was improved with all exercise types but the effects on CRF vary with cycle versus treadmill ergometer. Exercise failed to improve fatigue-related symptoms and muscle strength. Large RCTs are required to evaluate the effects of exercise in patients with BC in more detail.

A New Insight Into Nonbacterial Thrombotic Endocarditis: A Systematic Review of Cases.

BACKGROUND: Nonbacterial thrombotic endocarditis is characterized by the presence of organized thrombi on cardiac valves, often associated with hypercoagulable states. There is a paucity of data regarding the predictors of mortality in patients with nonbacterial thrombotic endocarditis. Our primary aim was to identify predictors of in-hospital mortality in patients with nonbacterial thrombotic endocarditis. METHODS: A systematic literature review of all published cases and case series was performed until May 2018 according to Preferred Reporting Items for Systematic Review and Meta-analyses statement guidelines. We applied random forest machine learning model to identify predictors of in-patient mortality in patients with nonbacterial thrombotic endocarditis. RESULTS: Our search generated a total of 163 patients (mean age, 46 ± 17 years; women, 69%) with newly diagnosed nonbacterial thrombotic endocarditis. The in-hospital mortality rate in the study cohort was 30%. Among the patients who died in the hospital, initial presentation of pulmonary embolism (12.2 vs. 2.6%), splenic (38.7 vs. 10.5%), and renal (40.8 vs. 9.6%) infarcts were higher compared to patients alive at the time of discharge. Higher rates of malignancy (71.4 vs. 39.4%, P = .0003) and lower rates of antiphospholipid syndrome (8.1 vs. 48.2%, P = .0001) were noted in deceased patients. Random forest machine learning analysis showed that older age, presence of antiphospholipid syndrome, splenic infarct, renal infarct, peripheral thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality. CONCLUSION: Patients admitted with nonbacterial thrombotic endocarditis have a high rate of in-hospital mortality. Factors including older age, presence of antiphospholipid syndrome, splenic/renal infarct, lower limb thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality in patients with nonbacterial thrombotic endocarditis.

Blood Cancer and the Heart: Light Chain Cardiomyopathy in Refractory Multiple Myeloma.

We report a case of a 57-year-old woman with a history of multiple myeloma (MM) and light chain (AL) amyloidosis who presented due to worsening dyspnea on exertion. Her MM has been refractory to multiple chemotherapy regimens and two autologous bone marrow transplantation. Diagnostic evaluations including serum kappa and lambda chains, echocardiogram, pyrophosphate cardiac scan, and cardiac magnetic resonance were indicative of a progression to AL cardiomyopathy. Addition of daratumumab to her regimen appeared to ameliorate the progression of AL cardiomyopathy. However, it was stopped due to adverse effects of pancytopenia and allergic reactions including skin rash and hives. She was hospitalized for heart failure exacerbation and died approximately 2 months following the discontinuation of daratumumab. This case highlights the late presentation of AL cardiomyopathy in refractory MM.

Diagnosis, treatment, and management of pericardial effusion- review.

The hemodynamic stability of the heart and pericardium are maintained by the pericardial fluid of volume ∼10-50 ml. Pericardial effusion is associated with the abnormal accumulation of pericardial fluid in the pericardial cavity. Numerous imaging techniques are utilized to evaluate pericardial effusion including chest X-ray, electrocardiogram, transthoracic echocardiography, computed tomography scan, cardiac magnetic resonance imaging, and pericardiocentesis. Once diagnosed, there are numerous treatment options available for the management of patients with pericardial effusion. These include various invasive and non-invasive strategies such as pericardiocentesis, pericardial window, and sclerosing therapies. In recent times, few studies have been conducted to evaluate the safety and efficacy of each approach in routine clinical practice. In this review, we review the role of different modalities in the diagnosis of pericardial effusion while highlighting existing therapies aimed at the management and treatment of pericardial effusion.

Does individualized guided selection of antiplatelet therapy improve outcomes after percutaneous coronary intervention? A systematic review and meta-analysis.

Background: The potential benefits of individualized guided selection of antiplatelet therapy over standard antiplatelet therapy in improving outcomes in patients undergoing percutaneous coronary intervention (PCI) have not been established. Therefore, we pooled evidence from available clinical trials to assess the effectiveness by comparing the two regimens in patients undergoing PCI. Methods: We queried two electronic databases, MEDLINE and Cochrane CENTRAL, from their inception to April 20, 2021 for published randomized controlled trials in any language that compared guided antiplatelet therapy, using either genetic testing or platelet function testing, versus standard antiplatelet therapy in patients undergoing PCI. The results from trials were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results: Eleven eligible studies consisting of 18,465 patients undergoing PCI were included. Pooled results indicated that guided antiplatelet therapy, compared to standard therapy, was associated with a significant reduction in the incidence of MACE [RR 0·78, 95% CI (0·62-0·99), P = 0·04], MI [RR 0·73, 95% CI (0·56-0.96), P = 0·03], ST [RR 0·66, 95% CI (0·47-0.94), P = 0·02], stroke [RR 0·71, 95% CI (0·50-1.00), P = 0·05], and minor bleeding [RR 0·78, 95% CI (0·66-0.91), P = 0·003]. Conclusions: Individualized guided selection of antiplatelet therapy significantly reduced the incidence of MACE, MI, ST, stroke, and minor bleeding in adult patients when compared with standard antiplatelet therapy. Our findings support the implementation of genetic and platelet function testing to select the most beneficial antiplatelet agent.

DOACs or VKAs or LMWH - What is the optimal regimen for cancer-associated venous thromboembolism? A systematic review and meta-analysis.

Background: Clinical guidelines have supported the use of direct anticoagulants (DOACs) for the treatment of cancer-associated venous thromboembolism (Ca-VTE). However, recent trials have reported increased bleeding risks associated with DOACs usage, raising concerns regarding its efficacy. Objectives: The authors conducted a meta-analysis to study the efficacy and safety of DOACs for the treatment of VTE in cancer patients, compared with Low-weight molecular heparin (LMWH) and Vitamin-K antagonists (VKAs). Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to June 17th, 2021.The primary outcomes studied were VTE recurrence and major bleeding. Results: A total of 8 randomized controlled trials (RCTs) enrolling almost 7000 patients were included. Direct oral anticoagulants significantly reduced VTE Recurrence in cancer patients when compared to patients treated with LMWH or VKAs (Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.83; P = 0.002; I2 = 26%). There were no statistically significant differences for major bleeding (HR 0.86, 95% confidence interval [CI] 0.56-1.33; P = 0.50; I2 = 34%), clinically relevant non-major bleeding (HR 1.23, 95% confidence interval [CI] 0.79-1.91; P = 0.35; I2 = 66%), pulmonary embolism (HR 0.71, 95% confidence interval [CI] 0.47-1.06; P = 0.10; I2 = 7%), and all-cause mortality (HR 0.98, 95% confidence interval [CI] 0.86-1.12; P = 0.78; I2 = 1%), between DOACs and LMWH. Conclusion: This analysis shows that DOACs are the optimal regimen to treat Ca-VTE. They have a similar to slightly increased bleeding risk compared with LMWH and are a safer alternative to VKAs.

Mortality after transcatheter aortic valve replacement for aortic stenosis among patients with malignancy: a systematic review and meta-analysis.

BACKGROUND: With advancements in cancer treatment, the life expectancy of oncology patients has improved. Thus, transcatheter aortic valve replacement (TAVR) may be considered as a feasible option for oncology patients with severe symptomatic aortic stenosis (AS). We aim to evaluate the difference in short- and long-term all-cause mortality in cancer and non-cancer patients treated with TAVR for severe AS. METHODS: Medline, PubMed, and Cochrane Central Register of Controlled Trials were searched for relevant studies. Patients with cancer who underwent treatment with TAVR for severe AS were included and compared to an identical population without cancer. The primary endpoints were short- and long-term all-cause mortality. RESULTS: Of 899 studies included, 8 met inclusion criteria. Cancer patients had significantly higher long-term all-cause mortality after TAVR when compared to patients without cancer (risk ratio [RR] 1.43; 95% confidence interval (CI) 1.26-1.62; P < 0.01). Four studies evaluated short-term mortality after TAVR and demonstrated no difference in it in patients with and without cancer (RR 0.72; 95% CI 0.47-1.08; P = 0.11). CONCLUSION: Patients with cancer and severe AS have higher long-term all-cause mortality after TAVR. However, we found no difference in short-term all-cause mortality when comparing patients with and without cancer. The decision to perform TAVR in cancer patients should be individualized based on life expectancy and existing co-morbidities.

Global and Regional Variations in Transthyretin Cardiac Amyloidosis: A Comparison of Longitudinal Strain and 99mTc-Pyrophosphate Imaging.

There are limited data on the head-to-head comparison of 99mTc-pyrophosphate (99mTc-PYP) and echocardiographic strain imaging in the assessment of transthyretin (TTR) cardiac amyloidosis. Methods: At Mayo Clinic Arizona, patients who had undergone both a 99mTc-PYP scan and a transthoracic echocardiogram within a 90-d period were retrospectively identified for chart review and strain imaging analysis. Patients were divided into 2 groups according to their 99mTc-PYP results (PYP-positive [PYP+] or PYP-negative [PYP-]) for the comparison. A standard 17-segment model was used for segmental, regional, and global longitudinal strain comparison. A P value of less than 0.05 was deemed significant. Results: In total, 64 patients were included, the mean age was 75.1 ± 13.0 y, and 57 (89.1%) were male. Comparing the PYP+ to the PYP- group, the left ventricular global longitudinal strain was significantly worse in the former (PYP+ vs. PYP-, -10.5 ± 2.6 vs. -13.1 ± 4.1; P = 0.003). PYP+ patients also had worse regional basal strain (-4.6 ± 2.6 vs. -8.8 ± 4.0, P < 0.001) and a trend toward worse midventricular strain (-9.6 ± 4.0 vs. -11.7 ± 4.4, P = 0.07), but there was no statistical difference in the apical region (-17.6 ± 4.73 vs. -19.0 ± 6.46, P = 0.35). This is consistent with an apex-sparing pattern shown by the relative apical longitudinal strain index (1.3 ± 0.5 vs. 1.0 ± 0.3, P = 0.008). Segment-to-segment analysis demonstrated a significant difference in strain between PYP+ and PYP- segments in 4 segments: basal inferior (P = 0.006), basal anterolateral (P = 0.01), apical septal (P = 0.002), and apical inferior (P = 0.001). Left ventricular diastolic dysfunction was significantly different, with 17 (77.3%) patients in the PYP+ group versus 15 (36.6%) in PYP- participants (P = 0.002). Conclusion: Our study suggested that 99mTc-PYP uptake is related to overall worse LV segmental, regional, and global longitudinal strain function, as well as diastolic function, compared with patients without 99mTc-PYP uptake. These data are important for helping clinicians learn about the echocardiographic function features related to 99mTc-PYP uptake and can help generate hypotheses for future studies.

Efficacy of Sodium-Glucose Cotransporter-2 inhibitors in heart failure patients treated with dual angiotensin receptor blocker-neprilysin inhibitor: An updated meta-analysis.

BACKGROUND: Recent data suggest that the prevalence of heart failure has increased to approximately 23 million people globally. With increasing advancement in pharmacotherapeutics, Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) have garnered attention among clinicians to treat Heart failure with reduced ejection fraction (HFrEF) in diabetic as well as non-diabetic patients. METHODS: MEDLINE, Scopus, Embase and Cochrane CENTRAL database were searched using relevant keywords and MeSH terms. Studies were considered only if they were randomized in nature and had a sample size >1000 HF patients. RESULTS: Our comprehensive search strategy yielded 864 articles, of which three RCTs met the inclusion criteria with a total population of 9696. Pooled analysis revealed an association between the use of SGLT2i and decreased frequency of primary outcome irrespective of background ARNI use (HR 0.73, 95% CI [0.58-0.93], p = 0.0106; HR 0.73, 95% CI [0.66-0.81], p < 0.0001). CONCLUSION: This meta-analysis provides substantial evidence, to safely use SGLT2i atop ARNI therapy in select HF patients to further improve outcomes.

Successful Treatment of Steroid-Refractory Checkpoint Inhibitor Myocarditis with Globulin Derived-Therapy: A Case Report and Literature Review.

Immune checkpoint inhibitor (ICI) monoclonal antibody drugs are an important interface of immunology and cancer biology with the intended goal to create cancer specific treatments with less systemic toxicity. Recognition of immune-related adverse events is critical and these include significant cardiovascular toxicity and myocarditis. Compared with other immune-related events, ICI associated myocarditis is rare but is associated with high mortality. The majority of cases present early in the course of therapy and patients can rapidly progress to fulminant myocarditis. Initially, the mainstay of treatment in patients with ICI-associated myocarditis is immunosuppressive therapy with glucocorticoids. For those who do not respond to steroids, the optimal treatment is unclear. This review summarizes the potential adjunctive treatment options for patients with steroid-refractory myocarditis by illustrating a case of myocarditis that was treated with Thymoglobulin and immunoglobulin.

Management of adults with coarctation of aorta.

Coarctation of the aorta (CoA) is a relatively common congenital cardiac defect often causing few symptoms and therefore can be challenging to diagnose. The hallmark finding on physical examination is upper extremity hypertension, and for this reason, CoA should be considered in any young hypertensive patient, justifying measurement of lower extremity blood pressure at least once in these individuals. The presence of a significant pressure gradient between the arms and legs is highly suggestive of the diagnosis. Early diagnosis and treatment are important as long-term data consistently demonstrate that patients with CoA have a reduced life expectancy and increased risk of cardiovascular complications. Surgical repair has traditionally been the mainstay of therapy for correction, although advances in endovascular technology with covered stents or stent grafts permit nonsurgical approaches for the management of older children and adults with native CoA and complications. Persistent hypertension and vascular dysfunction can lead to an increased risk of coronary disease, which, remains the greatest cause of long-term mortality. Thus, blood pressure control and periodic reassessment with transthoracic echocardiography and three-dimensional imaging (computed tomography or cardiac magnetic resonance) for should be performed regularly as cardiovascular complications may occur decades after the intervention.

Machine learning helps predict long-term mortality and graft failure in patients undergoing heart transplant.

OBJECTIVE: We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT). METHODS: Using the International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model's external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT. RESULTS: The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (n = 4161) and 28.1% (n = 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696-0.737) and 0.716 (95% CI 0.696-0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure. CONCLUSION: The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.

A Coronary Conundrum: Papillary Muscle Rupture and Ischemic Mitral Regurgitation Secondary to Coronary Thromboembolism in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that has a strong propensity for a hypercoagulable state and is known to be associated with venous and arterial thromboembolism. We describe an uncommon case of APS in the setting of non-Hodgkin's lymphoma, with thromboembolism, and a rare complication after an uncommon etiology of myocardial infarction. This case highlights the importance of early and appropriate type of anticoagulation to reduce the morbidity and mortality in patients with APS.

Decitabine Induced Delayed Cardiomyopathy in Hematologic Malignancy.

Decitabine is a pyrimidine analogue of nucleoside cytidine, used for the treatment of myelodysplastic syndromes, chronic myelogenous leukemia, and acute myelogenous leukemia. We present a case of cardiomyopathy associated with decitabine used for secondary acute myelogenous leukemia. The patient presented with new heart failure symptoms and an ejection fraction decline.

Radiation and the heart: systematic review of dosimetry and cardiac endpoints.

INTRODUCTION: Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects.  Authors aimed to review the recent literature on cardiac dosimetry and survival/cardiac endpoints. Areas covered: Systematic review of the literature in the past 10 years (2008-2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints.  Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma. Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause.  In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death.  For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors.  For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines.  Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival.  Symptomatic pericardial effusion typically occurs with doses >40 Gy.  Close follow-up and mitigation of cardiovascular risk factors are necessary after thoracic radiotherapy.

Reversal of coronary atherosclerosis: Role of life style and medical management.

Atherosclerotic coronary artery disease continues to be a major global health burden in developing and developed nations. Newer imaging techniques afford an accurate assessment of plaque burden and characteristics as well as the effects of treatment. Lifestyle interventions and pharmacotherapy remain the mainstay of non-interventional treatment of coronary atherosclerosis, with reversal seen in many studies. In addition, control of modifiable risk factors can be beneficial. As a better understanding of atherosclerosis pathophysiology is achieved, new therapeutic targets and combination therapies may join the armamentarium that promotes regression of atherosclerotic plaque. We present a review of the literature regarding lifestyle and medical therapies that can promote the reversal of coronary atherosclerosis.