Diagnostic Performance of Diastolic Hyperemia-Free Ratio Compared With Invasive Fractional Flow Reserve for Evaluation of Coronary Artery Disease.

Hyperemic and nonhyperemic pressure ratios are frequently used to assess the hemodynamic significance of coronary artery disease and to guide the need for myocardial revascularization. However, there are limited data on the diagnostic performance of the diastolic hyperemia-free ratio (DFR). We evaluated the diagnostic performance of the DFR compared with invasive fractional flow reserve (FFR). We performed a prospective, single-center study of 308 patients (343 lesions) who underwent DFR and FFR for evaluation of visually estimated 40% to 90% stenoses. Diagnostic performance of the DFR compared with FFR was evaluated using linear regression, Bland-Altman analysis, and receiver operating characteristic curves. The overall diagnostic accuracy of the DFR was 83%; the accuracy rates were 86%, 40%, and 95% when the DFR was <0.86, 0.88 to 0.90, and >0.93, respectively. The sensitivity, specificity, positive predicative value, and negative predictive value were 60%, 91%, 71%, and 87%, respectively. The Pearson correlation coefficient was 0.75 (p <0.05). The Bland-Altman analysis showed a mean difference of 0.09, and the area under the receiver operating characteristic curve was 0.88 (95% confidence interval 0.84 to 0.92, p <0.05). In conclusion, the DFR has a good diagnostic performance compared with FFR but 17% of the measurements were discordant. The diagnostic accuracy of the DFR was only 40% when the DFR was 0.88 to 0.90, suggesting that FFR may be useful in these arteries.

Coronary Revascularization in Patients With Cancer.

Purpose of review: The treatment of coronary artery disease (CAD) in cancer patients is an evolving landscape. Recent data emphasizes the importance of aggressive management of cardiovascular risk factors and diseases in improving cardiovascular health in this unique group of patients regardless of cancer type or stage. Recent findings: Novel cancer therapeutics such as immune therapies and proteasome inhibitors have been associated with CAD. Recent stent technologies may safely allow for shorter duration (< 6 months) of dual antiplatelet therapy post-percutaneous coronary interventions. Intracoronary imaging may be useful in the decision making process in terms of stent positioning and healing. Summary: Large registry studies have partially filled a gap left by the lack of randomized controlled trials in the treatment of CAD in cancer patients. Cardio-oncology is gaining traction as a major sub-specialty in the cardiology field given the release of the first European Society of Cardiology - Cardio-oncology guidelines in 2022.

Bioprosthetic valve monitoring in patients with carcinoid heart disease.

Background: Carcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement surgery appears to decrease all-cause mortality in patients with advanced CnHD, few studies have investigated the outcomes of patients after valve replacement. Methods: We conducted a multi-institution retrospective registry of patients who received both tricuspid and pulmonic bioprosthetic valve (TV/PV) replacements for advanced CnHD from November 2005 to March 2021. Patients were followed post-operatively with echocardiographic studies every 3 months. Carcinoid valvular heart disease scores were used to monitor valve degeneration. Neuroendocrine tumor treatment, their administration times, and associations with echocardiographic findings were recorded. Results: Of 87 patients with CnHD, 22 patients underwent simultaneous surgical TV and PV replacement. In 6 patients (27.3%), increased PV Vmax was the first echocardiographic manifestation of valve degeneration in the setting of occult neurohormonal release. Post-operative telotristat ethyl and peptide receptor radionuclide therapy appeared to stabilize PV Vmax. The PV Vmax showed consistent elevation in the entire patient population when compared to baseline, while bioprosthetic TV echocardiographic parameters were relatively unchanged throughout. Post-operative warfarin therapy did not affect the rate of PV degeneration, and no major bleeding was recorded during or after post-operative anticoagulation therapy. Conclusion: Bioprosthetic valve degeneration is common in CnHD. Monitoring with echocardiographic studies every 3 months, focusing on PV velocities, could identify patients with occult disease that very likely promotes valve degeneration. Novel neuroendocrine tumor therapies may have a beneficial impact on valve degeneration.

Coronary Stent Healing in Cancer Patients-An Optical Coherence Tomography Perspective.

Objective: This study assessed stent healing patterns and cardiovascular outcomes by optical coherence tomography (OCT) in cancer patients after drug-eluting stent (DES) placement. Background: Cancer treatment, owing to its cytotoxic and antiproliferative effects, could delay stent healing and increase stent thrombosis risk, especially when dual antiplatelet therapy (DAPT) is discontinued early for oncological treatment. OCT can assess stent endothelialization and other healing parameters, which may provide clinical guidance in these challenging scenarios. Methods: This single-center retrospective study enrolled all cancer patients who underwent OCT for assessment of vascular healing patterns after prior DES placement from November 2009 to November 2018. Primary study endpoints were stent healing parameters, including stent coverage, apposition, degree of expansion, neointimal hyperplasia heterogeneity, in-stent restenosis, stent thrombosis, and overall survival (OS). Results: A total of 67 patients were included in this study. Mean time between DES placement and OCT evaluation was 154 ± 82 days. Stent healing matched published values for DES in non-cancer patients (P ≥ 0.063). At 1 year, the OS was 86% (95% confidence interval [CI]: 78-96%) with 0% incidence of acute coronary syndrome. Advanced cancers and active chemotherapies were associated with inferior OS (P = 0.024, hazard ratio [HR]: 3.50, 95% CI: 1.18-10.42 and P = 0.026, HR: 2.65, 95% CI: 1.13-6.22, respectively), while stent healing parameters were unassociated with OS. Forty-one patients (61%) had DAPT duration ≤6 months. Conclusions: Stent healing of contemporary DES appears similar in cancer and non-cancer patients. Cardiovascular risk of cancer patients after DES placement can be managed to facilitate timely cancer therapies, as the underlying malignancy and active chemotherapy ultimately determine survival.

Transcatheter and surgical aortic valve replacement impact on outcomes and cancer treatment schedule.

BACKGROUND: Recent data suggest that transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis (AS) is viable in cancer patients. TAVR may be preferred in cancer patients due to its minimally invasive nature and smaller impact on oncologic therapies compared to SAVR. Objectives We sought to determine if TAVR is an acceptable alternative to SAVR in cancer patients and whether TAVR allows for earlier initiation or resumption of anti-cancer therapies. METHODS: Cancer patients in a tertiary cancer center diagnosed with severe AS were retrospectively included. Patients accepted by the heart team underwent either TAVR or SAVR, while remaining patients received medical therapy alone. Time intervals to initiation of cancer treatment and the impact of cancer treatment on the replaced valves were recorded. Logistic regression was performed to determine the impact of treatment strategy on overall survival (OS) in all 3 subgroups. RESULTS: One hundred and eighty-seven cancer patients diagnosed with severe AS were identified. AVR was associated with better OS compared to medical therapy alone (p < 0.0001). TAVR was associated with better OS at 72 months (HR = 0.468, p < 0.001) compared to medical therapy alone, with no difference in OS observed between SAVR and TAVR. Time intervals to initiation of cancer treatments were shorter in the TAVR group, with no valve deterioration or infection observed in all groups. CONCLUSION: Cancer patients with severe AS benefit from AVR. TAVR is a viable alternative to SAVR in high-risk cancer patients to prolong survival and allow for earlier administration or resumption of anti-neoplastic therapies.

Cancer treatment resumption in patients with new-generation drug-eluting stents.

OBJECTIVE: Percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DESs) may provide survival benefits to the cancer population undergoing PCI by expediting cancer treatment due to improved safety profile. We aimed to assess the safety of starting or resuming cancer treatment within 6 months of DES placement. We also compared the impact of different DES types on the overall survival (OS) in cancer patients and to identify a safe threshold for dual antiplatelet therapy (DAPT) discontinuation. METHODS: Cancer patients at our institution undergoing PCI with DES from December 2014 to June 2017 were included. Baseline demographics, DAPT duration, malignancy type, stage, and treatment were retrospectively analyzed. Univariate Cox regression was used to pinpoint baseline characteristics that correlated with OS. Survivorship was determined by Kaplan-Meier analysis, and the log-rank test was used to compare OS among DES types. RESULTS: Seventy-five patients were included. Of these, 45 had biodegradable polymer DES (Synergy) and 30 patients had durable polymer DES (Resolute Integrity, Xience, Ion, or Promus). Mean duration of follow-up was 1367 ± 334 days. There were two minor bleeding complications. No statistically significant differences in OS were found among different stent brands. Discontinuation of aspirin, early P2Y12 inhibitor discontinuation, and advanced cancer were significantly associated with OS. DAPT discontinuation <6 months after PCI was not associated with stent thrombosis or in-stent restenosis. There were two major adverse cardiac events: one in-stent restenosis while on DAPT for >12 months (attributed to radiation-induced heart disease) and one myocardial infarction and death. Of patients who resumed or started cancer treatment (chemotherapy, radiation therapy, or surgery) after PCI, all but one did so within 6 months of PCI, and most of them as early as 2 weeks. CONCLUSION: Patients may resume cancer treatment <6 months after PCI. We suggest that DAPT may be safely interrupted as early as 6 months, but additional longitudinal studies are needed.

Acute myocardial infarction in a high-risk cancer population: Outcomes following conservative versus invasive management.

BACKGROUND: The benefits of invasive versus noninvasive management in oncology patients with acute myocardial infarction (AMI) are unclear. We aimed to retrospectively determine outcome differences between conservative and invasive management of AMI in cancer patients. METHODS: Patients from our institution between March 2016 and December 2018 with type 1 and type 2 AMI (excluding STEMI) were classified into 2 groups: medical therapy only and invasive strategies. Analyzed outcomes were overall survival (OS), procedural complications, subsequent events, and hospice referral. Kaplan-Meier method and log-rank test were used to compare OS between subgroups. Cox proportional hazards regression analyses were conducted to find factors associated with OS. RESULTS: We included 201 patients. Type 1 MI was seen in 152 patients (76%) and type 2 MI in 49 (24%). Median OS was 13 months. Most presented with symptoms other than dyspnea or chest pain (49%) and with ECG revealing changes other than ST-segment depression and T-wave inversion (62%). Patients with type 2 MI had worse OS than patients with type 1 MI (HR = 2.3, p = 0.0002). Early coronary angiography (≤72 h; HR = 0.327, p < 0.0001), late coronary angiography (>72 h; HR = 0.496, p = 0.0426), and percutaneous coronary intervention (HR = 0.481, p = 0.0116) were associated with better OS than noninvasive approaches. Single and dual agent antiplatelet therapy, beta blockers, and statins were each associated with better OS. CONCLUSIONS: Cancer patients without STEMI who underwent invasive treatment for AMI had better OS compared with those treated only medically, with the highest benefit when coronary angiography was performed within 72 h of admission for AMI.

Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy.

Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.

Identifying Hemostatic Thresholds in Cancer Patients Undergoing Coronary Angiography Based on Platelet Count and Thromboelastography.

Objectives: To evaluate the role of platelet count and thromboelastogram (TEG) in the treatment of thrombocytopenic cancer patients with suspected coronary artery disease (CAD). Background: Cancer patients with CAD and thrombocytopenia are often treated non-invasively (i.e., without coronary angiography when clinically indicated) due to perceived high risk of bleeding. We sought to evaluate coagulability based on TEG and determine if platelet count and TEG could predict bleeding risk/mortality among cancer patients undergoing coronary angiography (CA). Methods: Baseline demographics, platelet count, and TEG parameters were recorded among cancer patients that underwent CA and had a concomitant TEG. Logistic regression and univariate proportional hazards regression analysis were performed to determine the impact of platelet count and coagulability on 24-month overall survival (OS). Results: All patients with platelet count <20,000/mm3 and nearly all patients with platelet count 20,000-49,000/mm3 were hypocoagulable based on TEG results. In contrast, nearly all patients with platelet counts of 50,000-99,999/mm3 had normal TEG results and OS similar to those with platelet counts of ≥100,000/mm3. Coagulability based on TEG was not associated with OS. However, a platelet count of <50,000/mm3 was associated with worse 24-month OS (hazard ratio = 2.76; p = 0.0072) when compared with a platelet count of ≥100,000/mm3. No major bleeding complications were observed in all groups. Conclusion: The majority of cancer patients with platelet counts of <50,000/mm3 were hypocoagulable based on TEG and had worse OS at 24 months. The relatively normal TEGs in the >50,000/mm3 groups, as well as the improved survival, suggest that with appropriate clinical indication and risk/benefit assessment, a cut-off of 50,000/mm3 platelets can be considered for CA in cancer patients.

Cardiac Interventional Procedures in Cardio-Oncology Patients.

Comorbidities specific to the cardio-oncology population contribute to the challenges in the interventional management of patients with cancer and cardiovascular disease (CVD). Patients with cancer have generally been excluded from cardiovascular randomized clinical trials. Endovascular procedures may represent a valid option in patients with cancer with a range of CVDs because of their minimally invasive nature. Patients with cancer are less likely to be treated according to societal guidelines because of perceived high risk. This article presents the specific challenges that interventional cardiologists face when caring for patients with cancer and the modern tools to optimize care.

Percutaneous closure of a large atrial septal defect in a child with severe dextroscoliosis: A case report.

In this study, we present the case of an 11-year-old child with cachexia, severe dextroscoliosis, pectus carinatum, secondary restrictive pulmonary disease, and an incidental finding of a large ostium secundum atrial septal defect (ASD) that was identified on preoperative assessment for surgical correction of the spinal deformity. Transthoracic and transesophageal echocardiography confirmed significant left-to-right shunting with a pulmonary blood flow to systemic blood flow ratio (Qp/Qs) of 3.18 through a 14 mm defect with good circumferential rims, larger than 5 mm. Despite significant left-to-right shunting, the defect was found prior to the development of pulmonary hypertension or right heart enlargement. The decision to close the atrial septal defect by percutaneous intervention was preferred over surgical closure, due to the restrictive pulmonary physiology and low body mass index (12.6 kg/m2). Percutaneous closure of the ASD was successfully performed under general anesthesia using an Occlutech Figulla Flex II ASD device, with no residual shunt. Surgical correction of the dextroscoliosis was subsequently performed with good results. A comprehensive clinical and echocardiographic evaluation is needed in patients with skeletal abnormalities in order to rule out associated congenital heart defects, which may impose therapeutic challenges.

The Onco-cardiologist Dilemma: to Implant, to Defer, or to Avoid Transcatheter Aortic Valve Replacement in Cancer Patients with Aortic Stenosis?

PURPOSE OF REVIEW: Aging is associated with an increased prevalence of both cancer and heart disease. The progression of aortic valve calcification to aortic stenosis may be accelerated by both cardiovascular risk factors and cancer treatments, such as radiotherapy with mediastinal involvement. Symptomatic aortic stenosis is occasionally diagnosed in cancer patients undergoing cardiovascular evaluation; likewise, cancer is often recognized during assessment preceding aortic valve interventions. In these complex cases, physicians face difficult treatment decisions. Due to a myriad of clinical presentations of cancer and valve disease, specific guidelines for this patient population are not currently in place. Management is currently based on clinical judgment, on an individual basis. RECENT FINDINGS: Patients with cancer in remission or with a favorable prognosis should be treated according to current cardiovascular guidelines. In these patients, aortic valve replacement can be performed either by surgery or transcatheter. Significant challenges arise in patients with active cancer, especially those receiving anti-cancer treatment. Recent data suggests that these patients can be offered aortic valve replacement, with a trend of favoring the transcatheter route in order to minimize perioperative risk and complications associated with major surgery. Patients with advanced cancer and severe aortic stenosis should be offered palliative care and can benefit from aortic balloon valvuloplasty if indicated. Modern cancer treatments associated with improved long-term prognosis may allow the appropriate cure of aortic stenosis. We discuss the protocol, outcomes, and evolving recommendations of aortic valve replacement in cancer patients with aortic stenosis.

The 1, 2, 3, 4 of carcinoid heart disease: Comprehensive cardiovascular imaging is the mainstay of complex surgical treatment.

Carcinoid heart disease (CHD) is a rare complication of neuroendocrine tumors, most commonly involving the tricuspid and pulmonary valves. The mitral and aortic valves can also be affected, albeit rarely, in certain circumstances such as the presence of a patent foramen ovale. Transthoracic echocardiogram is generally considered the key imaging modality, but cardiac magnetic resonance can add valuable information, particularly in the assessment of pulmonary valve function or multivalvular disease. Previously, surgical management of CHD carried high mortality, as a result of less advanced surgical techniques and of late intervention, reserved for cases of severely symptomatic heart failure. Modern approaches are associated with significantly improved survival rates, even in multivalvular, complex cases. Valve replacement can provide survival benefits in patients with CHD, but the optimal timing for the intervention is uncertain, with data suggesting a trend of improved survival with earlier intervention. A comprehensive imaging assessment may contribute to establishing optimal surgical timing. This approach may shift the main driver of mortality from the cardiac involvement to the primary malignancy and lead to improved outcomes. We present a series of imaging findings in CHD patients who have successfully undergone simultaneous surgical replacement with bioprosthetic valves of 1 to 4 heart valves. The surgical decision in these patients was based on a multimodality cardiovascular approach, including transthoracic and transesophageal echocardiography and cardiac magnetic resonance. The patients had uncomplicated postoperative courses, significant symptomatic relief from heart failure symptoms, and there was no cardiovascular mortality. Early recognition of CHD with a multimodality approach may improve outcome, even in complex cases. Bioprosthetic valves are generally preferred in CHD due to decreased need for anticoagulation, despite concern for premature degeneration. A collaboration between the Oncology and Cardiology teams is essential for the long-term management of CHD patients.

A Cancer Paradox: Machine-Learning Backed Propensity-Score Analysis of Coronary Angiography Findings in Cardio-Oncology.

OBJECTIVES: Cancer has been proposed as a cardiovascular risk factor. We aimed to assess the cardiovascular risk profile and coronary angiography (CA) findings of cancer patients and compare them to those of patients without cancer. METHODS: A retrospective case-control analysis was conducted on randomly enrolled cancer and non-cancer patients from a high-volume cardio-oncology center and a tertiary cardiology center, respectively, who underwent CA from April 2008 to June 2018. Baseline demographics, laboratory findings, cancer status and treatment, and current and prior CA findings were collected by chart review. Coronary artery disease (CAD) burden was assessed with machine-learning (neural-network) guided propensity-score adjusted multivariable regression, controlling for known CAD confounders. RESULTS: Of the 480 enrolled patients, a total of 240 (50%) had cancer. Fewer cancer vs non-cancer patients had clinically significant lesions on the left anterior descending artery (25.00% vs 39.17%, respectively; P<.01) and left circumflex artery (15.83% vs 30.00%, respectively; P<.001). Left main and right coronary artery disease prevalence was similar. Subjects with cancer were less likely to have multivessel CAD (odds ratio, 0.53; 95% confidence interval, 0.29-0.98; P=.04) and significant left circumflex artery lesions (odds ratio, 0.47; 95% confidence interval, 0.26-0.85; P=.01), independent of known CAD confounders. CONCLUSIONS: Patients with cancer have a lower burden of angiographically detected coronary atherosclerosis. Cancer patients are more likely than non-cancer patients to undergo CA for reasons other than suspicion of CAD. Further studies should prospectively analyze the impact of cancer on the development of CAD.

Fulminant Vascular and Cardiac Toxicity Associated with Tyrosine Kinase Inhibitor Sorafenib.

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

An update on the management and outcomes of cancer patients with severe aortic stenosis.

OBJECTIVES: We compared the outcomes of aortic valve replacement (AVR) by transcatheter (TAVR) and surgical (SAVR) routes with those of optimal medical management in patients with cancer and severe aortic stenosis (AS). BACKGROUND: Cancer therapy requires optimal cardiac output; however, the treatment of AS in cancer patients is not established. METHODS: Cancer patients with severe AS during January 2009 through February 2018 at a large cancer center were identified. Demographic and clinical characteristics including previous or active cancer diagnosis, history of chest radiotherapy, AS treatment, and survival were collected. Univariate Cox proportional hazards regression, the Kaplan-Meier analysis, and log-rank tests were used to compare overall survival (OS) between AS treatment groups. RESULTS: Sixty-five cancer patients with severe AS were identified; 28 received optimal medical treatment alone, 30 received TAVR, and seven received SAVR. The patients were predominantly male (n = 44, 68%) with a mean age of 71.17 years. The median OS was 9.87 months, and the most common cause of death was cancer (n = 29, 94% of deaths). AVR was associated with a lower risk of death than no AVR (hazard ratio [HR] 0.38, P = 0.007), and patients who underwent TAVR (HR 0.36, P = 0.01) had better survival than those with no AVR. Malignancy type, stage, and treatment were not associated with OS. CONCLUSIONS: Patients with cancer and severe AS who underwent AVR, predominantly TAVR, experienced better survival than those who had no AVR regardless of cancer type or cancer treatment. TAVR may be considered in patients with cancer and AS.