Cardiotoxicity of Anti-Cancer Radiation Therapy: a Focus on Heart Failure.

PURPOSE OF REVIEW: As the percentage of patients achieving long-term survival following treatment of their cancer grows, it is increasingly important to understand the long-term toxicities of cancer-directed treatment. In this review, we highlight the recent findings regarding radiation-induced cardiotoxicity across multiple disease sites, with a particular focus on heart failure. RECENT FINDINGS: Despite its relative lack of study historically, radiation-induced heart failure has now recently been implicated in several studies of breast cancer, lung cancer, esophageal cancer, and lymphoma as a non-trivial potential consequence of thoracic radiotherapy. Data regarding specific cardiac dosimetric endpoints relevant to cardiotoxicity continue to accumulate. Radiation-induced heart failure is a rare but significant toxicity of thoracic radiotherapy, that is likely underreported. Important areas for future focus include understanding the interplay between thoracic radiotherapy and concurrent cardiotoxic systemic therapy as well as development of potential mitigation strategies and novel therapeutics.

Clinical characteristics, evaluation and outcomes of chylopericardium: a systematic review.

OBJECTIVE: Chylopericardium (CPE) is a rare condition associated with accumulation of triglyceride-rich chylous fluid in the pericardial cavity. Due to minimal information on CPE within the literature, we conducted a systematic review of all published CPE cases to understand its clinical characteristics, management and outcomes. METHODS: We performed a literature search and identified cases of patients with CPE from 1946 until May 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified relevant articles for pooled analyses of clinical, diagnostic and outcome data. RESULTS: A total of 95 articles with 98 patients were identified. Patient demographics demonstrated male predominance (55%), with a mean age of 37±15 years. Time from symptom onset to diagnosis was 5 (Q1 4.5, Q3 14) days, with 74% of patients symptomatic on presentation. Idiopathic CPE (60%) was the most common aetiology. Cardiac tamponade secondary to CPE was seen in 38% of cases. Pericardial fluid analysis was required in 94% of cases. Lymphangiography identified the leakage site in 59% of patients. Medical therapy (total parenteral nutrition, medium-chain triglycerides or octreotide) was undertaken in 63% of cases. In our cohort, 32% progressed towards surgical intervention. During a median follow-up of 180 (Q1 180, Q3 377) days, CPE recurred in 16% of cases. Of the patients with recurrence, 10% were rehospitalised. CONCLUSION: CPE tends to develop in younger patients and may cause serious complications. Many patients fail medical therapy, thereby requiring surgical intervention. Although overall mortality is low, associated morbidities warrant close follow-up and possible reintervention and hospitalisations.

Disparities in the Prescription of Statins in the Primary Care Setting: A Retrospective Observational Study.

Despite the high disease burden of atherosclerosis, evidence exists for the disparity in the prescription of guideline-indicated medications between genders, racial groups, socioeconomic groups, and ages. We aim to perform a retrospective study looking at the disparity in statin prescription for primary and secondary prevention in these groups. Data were collected from a single center and included patients with an LDL level >190 mg/dL, diagnosis of diabetes mellitus with LDL level >70 mg/dL, and diagnosis of cardiovascular disease regardless of LDL level. Patients older than 75 or younger than 21 were excluded from the study. Complex samples multivariable logistic and linear regression models were used to calculate the adjusted odds ratio and 95% confidence interval. The total study population was n = 56,995. Of those, 57.89% (n = 32,992) were female. Only 59.56 % of these patients for whom statin therapy was indicated received it. Most patients were White (53.21%) followed by African Americans (35.98%), Asians (2.43%), American Indian/Native Alaskans (0.40%), and Native Hawaiian/Pacific Islander (0.18%). There is a clear disparity in statin prescription favoring males, the elderly, and people of white ethnicity. Interestingly, Asians were more likely to be prescribed statins as opposed to whites. Self-pay patients were more likely to receive statins than patients on Medicare.Despite being indicated, Statins are under prescribed. Disparities based on race, gender, and insurance type mirror previous trends in the literature. Some results have shown a reversal in trends such as the higher prescription for Asian-Americans. Multiple patient-specific, provider-related, institutional factors might explain these disparities and must be investigated.

Utilization of Non-Gated Chest Computed Tomography Scans in Predicting Acute Coronary Occlusion in Out-of-Hospital Cardiac Arrest.

Coronary artery disease is thought to be responsible for up to 60%-80% of out-of-hospital cardiac arrests. The utility of Computed Tomography (CT) chest when it comes to identifying acute coronary occlusion in patients following an arrest has not been studied. We evaluated whether myocardial perfusion on a contrast-enhanced chest CT performed for a non-cardiac cause can predict culprit coronary occlusion as the cause of cardiac arrest and if the absence of a perfusion defect can exclude an ischemic etiology. A retrospective cohort of 53 consecutive patients presenting with VT or VF arrest and successful resuscitation who had contrast chest CT before angiography were identified. CT scans were reviewed for myocardial perfusion defects by a cardiologist and radiologist blinded to angiogram findings. CT results were then compared with angiograms. On coronary angiography, 22 (42%) of the patients presenting with out-of-hospital arrest had critical stenosis. Sensitivity and specificity of perfusion defect on CT in identifying critical stenosis on catheterization was 0.45, 95% CI [0.24, 0.68] and 0.77, 95% CI [59%, 90%], respectively. The positive likelihood ratio was 2.01 (0.91, 4.46) and the negative likelihood ratio was 0.70 (0.46, 1.08). The diagnostic accuracy was 64.2%. Our study did not show much utility for the use of myocardial perfusion defect on an incidental pre-angiography contrast chest CT to predict acute thrombotic occlusion in out-of-hospital cardiac arrest patients. However, this shouldn't discourage further studies evaluating the utility of contrast-enhanced CT images in predicting acute coronary occlusion.

Postdischarge-to-30-Day Mortality Among Patients Receiving MitraClip: A Systematic Review and Meta-Analysis.

Background: MitraClip (MC) implantation is the recommended treatment for severe symptomatic mitral regurgitation in patients not responding to medical therapy and at prohibitive surgical risk. It is important to quantify immediate mortality during postdischarge-to-30-day period so as to improve the procedural outcomes. Hence, we aim to identify the incidence of postdischarge-to-30-day mortality and its associated predictors using the technique of meta-analysis. Methods: We searched Medline, Embase, and Cochrane CENTRAL databases from inception until July 3, 2019 for studies reporting mortality prior to discharge, at 30 days and 1 year after MC implantation. The primary outcome was postdischarge-to-30-day all-cause mortality. Results: Of 2394 references, 15 studies enrolling 7498 patients were included. Random effects analysis showed that all-cause cumulative inpatient, 30-day, and 1-year mortality was 2.40% (2.08, 2.77; I2 = 0%), 4.31% (3.64, 5.09, I2 = 41.9%), and 20.71% (18.32; 23.33, I2 = 81.5%), respectively. The postdischarge-to-30-day mortality was 1.70% (95% confidence interval: 1.0, 2.70; I2 = 84%). A total of 71.50% of deaths (95% confidence interval: 36.80-91.50, I2 = 63%) in the postdischarge-to-30-day period were due to cardiac etiology. On meta-regression, pre-MC left ventricular ejection fraction (p = 0.003), Log.Euroscore (p = 0.047), Society of Thoracic Surgeons Predicted Risk of Mortality (p < 0.001), and prolonged ventilation >48 ​hours (p < 0.001) were found to be its significant predictors. Conclusions: Our meta-analysis reports an additional mortality of ∼2% immediately after MC implantation during the postdischarge-to-30-day period. Majority of deaths occurred due to cardiac causes. Pre-MC left ventricular ejection fraction, Log.Euroscore, Society of Thoracic Surgeons Predicted Risk of Mortality score, and prolonged ventilation were found to be its significant predictors. Further studies are needed to better understand the causes of this early mortality to maximize benefits of this important therapy.

Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Preserved Systolic Function.

BACKGROUND: A high proportion of patients with hypertrophic cardiomyopathy (HCM) have evidence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). OBJECTIVES: This study sought to assess the incremental prognostic utility of LGE in patients with HCM. METHODS: We studied 1,423 consecutive low-/intermediate-risk patients with HCM (age ≥18 years) with preserved left ventricular (LV) ejection fraction (mean age 66 ± 14 years, 60% men) who underwent transthoracic echocardiography (TTE) (including dimensions and LV outflow tract gradients) and CMR (including LGE as a % of LV mass) at our center between January 2008 and December 2015. The primary composite endpoint was sudden cardiac death (SCD) and appropriate implantable cardioverter-defibrillator discharge. The percent 5-year SCD risk score was calculated. RESULTS: The mean 5-year SCD risk score was 2.3 ± 2.0. Mean maximal LV outflow tract gradient (TTE) was 70 ± 55 mm Hg (median 74 mm Hg [interquartile range (IQR): 10 to 67 mm Hg]); indexed LV mass and LGE (both on CMR) were 91 ± 10 g/m2 and 8.4 ± 12% (IQR: 0% to 19%); 50% had LGE on CMR. Of these, 458 were nonobstructive and 965 were obstructive (of which 686 were underwent myectomy). At 4.7 ± 2.0 years of follow-up, 60 (4%) met the composite endpoint. On quadratic spline analysis, LGE ≥15% was associated with increased risk of composite events. In the obstructive subgroup, on competing risk regression analysis, ≥15% LGE (subhazard ratio: 3.04 [95% confidence interval: 1.48 to 6.10]) was associated with a higher rate and myectomy (subhazard ratio: 0.44 [95% confidence interval: 0.20 to 0.76]) was associated with a lower rate of composite endpoints (both p < 0.01). Similarly, sequential addition of LGE ≥15% and myectomy to % 5-year SCD risk score improved the log likelihood ratios from -227.85 to -219.14 (chi-square 17) and to -215.14 (chi-square 8; both p < 0.01). Association of %LGE with composite events was similar even in myectomy and nonobstructive subgroups. CONCLUSIONS: In low-/intermediate-risk adult patients with HCM (obstructive, myectomy, and nonobstructive subgroups) with preserved systolic function, %LGE was significantly associated with a higher rate of composite endpoint, providing incremental prognostic utility.

Outcomes and Management of Patients With Severe Pulmonary Vein Stenosis From Prior Atrial Fibrillation Ablation.

BACKGROUND: Pulmonary vein (PV) stenosis remains a feared complication of atrial fibrillation ablation. Little is known about outcomes in patients with severe PV stenosis, especially about repeat ablations. METHODS: In 10 368 patients undergoing atrial fibrillation ablation (2000-2015), computed tomography scans were obtained 3 to 6 months after ablation. The clinical outcomes in severe PV stenosis were determined. RESULTS: Severe PV stenosis was diagnosed in 52 patients (0.5%). This involved mostly the left superior PV (51% of severely stenosed veins). Percutaneous interventions were performed in 43 patients, and complications occurred in 5: 3 PV ruptures, 1 stroke, and 1 phrenic injury. Over a median follow-up of 25 months, 41 (79%) patients remained arrhythmia free. Repeat ablation was performed in 15 patients (7 from the main series and 8 from prior ablation at other institutions); of whom 10 had PV stents in place. Conduction recovery was noted in all but 2 of the stenosed or stented PVs, and areas with recovery were targeted with antral ablation. Lasso entrapment within stents occurred in 2 patients but eventually freed without complications. After redo ablation, preplanned stenting was performed in 3 patients and computed tomographic scans showed progression of concomitant stenoses in 1 patient (moderate to severe). No procedure-related deaths occurred. CONCLUSIONS: The incidence of severe PV stenosis is low but remains associated with significant morbidity. In patients with recurrent arrhythmia, conduction recovery at the stenosed or stented veins is common. Care must be taken to ablate antrally to avoid stenosis progression. In patients with prior PV stents, we suggest to avoid using Lasso.

Advances in Cardiovascular Health in Women over the Past Decade: Guideline Recommendations for Practice.

Cardiovascular disease (CVD) remains the number one cause of death in women. It is estimated that 44 million women in the United States are either living with or at risk for heart disease. This article highlights the recent significant progress made in improving care, clinical decision-making, and policy implications for women with CVD. We provide our perspective supported by evidence-based advances in cardiovascular research and clinical care guidelines in seven areas: (1) primary CVD prevention and community heart care, (2) secondary prevention of CVD, (3) stroke, (4) heart failure and cardiomyopathies, (5) ischemia with nonobstructive coronary artery disease, (6) spontaneous coronary artery dissection, and (7) arrhythmias and device therapies. Advances in these fields have improved the lives of women living with and at risk for heart disease. With increase awareness, partnership with national organizations, sex-specific research, and changes in policy, the morbidity and mortality of CVD in women can be further reduced.

Verification of Heart Disease: Implications for a New Heart Transplantation Allocation System.

OBJECTIVES: This study sought to determine the accuracy of the pre-transplantation clinical diagnosis of heart disease in the United Network for Organ Sharing (UNOS) database. BACKGROUND: Because survival on the heart transplantation waitlist depends on underlying heart disease, a new allocation system will include the type of heart disease. Accuracy of the pre-transplantation clinical diagnosis and the effect of misclassification are unknown. METHODS: We included all adults who received transplants at our center between January 2009 to December 2015. We compared the pre-transplantation clinical diagnosis at listing with pathology of the explanted heart and determined the potential effect of misclassification with the proposed allocation system. RESULTS: A total of 334 patients had the following clinical cardiac diagnoses at listing: 148 had dilated cardiomyopathy, 19 had restrictive cardiomyopathy, 103 had ischemic cardiomyopathy, 24 had hypertrophic cardiomyopathy, 11 had valvular disease, 16 had congenital heart disease (CHD), and 13 patients had a diagnosis of "other." Pathology of the explanted hearts revealed 82% concordance and 18% discordance (10% coding errors and 8% incorrect diagnosis). The most common incorrect diagnoses were sarcoidosis (66%), arrhythmogenic right ventricular dysplasia (60%), and other causes of predominately right-sided heart failure (33%). Among the misclassified diagnoses, 40% were listed as UNOS status 2, 8% remained at status 2 at transplantation, and only sarcoidosis and CHD were potentially at a disadvantage with the new allocation. CONCLUSIONS: There is high concordance between clinical and pathologic diagnosis, except for sarcoidosis and genetic diseases. Few misclassifications result in disadvantages to patients based on the new allocation system, but rare diseases like sarcoidosis remain problematic. To improve the UNOS database and enhance outcome research, pathology of the explanted hearts should be required post-transplantation.

Evaluation of left ventricular diastolic function profile in patients with pulmonary hypertension due to heart failure with preserved ejection fraction.

BACKGROUND: Echocardiography plays an important role in the diagnostic work up of heart failure with preserved ejection fraction (HFpEF). We sought to determine the left ventricular (LV) diastolic profile by echocardiography in patients diagnosed with pulmonary hypertension (PH) due to PH-HFpEF. HYPOTHESIS: The study of LV diastolic function by echocardiography has limitations in patients with HFpEF and PH, and certain LV diastolic determinations convey a worse prognosis. METHODS: We included patients with postcapillary PH and diagnosis of PH-HFpEF. Investigators reviewed Doppler echocardiograms completed within 3 months of the diagnostic right heart catheterization. RESULTS: We included 149 patients with a mean ± standard deviation age of 63 ± 14 years; 58% were women. LV diastolic function profile was determined as normal (41%), grade I (34%), and grade II and grade III (25%). Pulmonary artery pressure and pulmonary vascular resistance were higher and cardiac output lower in patients with LV diastolic dysfunction profile; however, pulmonary artery wedge pressure was not significantly different among grades of LV diastolic function. Although there was an association between the presence of LV diastolic dysfunction profile and long-term survival (P = 0.03), it disappeared when adjusting for age and gender. Right ventricular (RV) dysfunction, paradoxical septal motion, and higher RV systolic pressure remained the only variables significantly associated with poor survival. CONCLUSIONS: The profile of LV diastolic dysfunction by conventional echocardiography is highly variable in patients with PH-HFpEF and has no significant impact on long-term survival. A more severe RV function and higher right ventricle systolic pressure were associated with worse survival.

Hospital Readmissions Following Endovascular Therapy for Critical Limb Ischemia: Associations With Wound Healing, Major Adverse Limb Events, and Mortality.

BACKGROUND: The significance of hospital readmission after endovascular therapy for critical limb ischemia (CLI) is not well established. We sought to investigate the incidence, timing, and causes of readmissions after endovascular therapy for CLI and whether readmission is associated with major adverse limb events (MALE) or mortality. METHODS AND RESULTS: This was a retrospective study of 252 patients treated with endovascular therapy for CLI. During median follow-up of 381 days (interquartile range [IQR], 115-718), 140 (56%) were readmitted, with median time to readmission of 83 days (IQR, 33-190). Readmission within 30 days occurred in 14% of patients (n=35; 25% of readmissions). Most readmissions occurred between 30 and 180 days (n=67; 48% of readmissions). The most frequent reason for readmission was unhealed wounds (n=63; 45% of readmissions). Independent predictors of readmission by Cox proportional hazards analysis were unhealed wounds, presence of multiple wounds, age ≥70, female sex, hemodialysis, and history of heart failure (P<0.05 for each). By Kaplan-Meier analysis, readmission was greatest in patients with unhealed wounds, followed by patients who never had a wound, and lowest in patients whose wounds completely healed (P<0.0001 overall, and P<0.01 between groups). After multivariable adjustment, readmission remained an independent predictor of composite MALE (major amputation, bypass, or endarterectomy) or mortality (adjusted hazard ratio, 3.1; 95% CI, 1.5-6.5; P=0.002). CONCLUSIONS: Most readmissions occur 30 and 180 days after endovascular therapy for nonprocedural reasons. Unhealed wounds are an independent risk factor for readmission. Readmission is associated with increased MALE and mortality after endovascular therapy for CLI.