High Incidence of Cardiovascular Disease in Patients With Oesophageal Cancer-A Registry-Based Cohort Study.

BACKGROUND: The cardiovascular disease (CVD) burden among patients with oesophageal cancer (EC) treated with curative intent is unclear. AIM: To determine CVD incidence and all-cause mortality in patients with EC. METHOD: Danish national health registries were used to identify patients diagnosed with primary EC between 2008 and 2018. Each EC patient was matched with 10 individuals from the general population. The primary endpoint was a CVD hospital contact (CVD-HC), either admission or outpatient contact. Cox proportional hazard regression models were used to compare the risk of incident CVD-HCs between the cohorts. RESULTS: The study included 1,525 patients with EC and 15,250 individuals from the general population. Patients with EC had a post-diagnosis one-year adjusted hazard ratio (HR) of CVD-HC of 6.1 (95% confidence intervals [CIs] 5.6-6.8) compared with the general population. During the next nine years, the risk of CVD-HC was comparable between the two cohorts, with an adjusted HR of 1.0 (95% CI 0.9-1.3). Patients with EC, and particularly those with prevalent CVD, had a high risk of atrial fibrillation, ischaemic heart disease, and venous thromboembolism within the first year after EC diagnosis. Prevalent CVD among patients with EC was not associated with higher mortality. CONCLUSIONS: CVD morbidity was transiently increased in the first year following EC diagnosis compared with the general population. All-cause mortality risks were high but did not appear to be affected by prevalent CVD. The very high risk of CVD in patients with primary EC to be treated with curative intent calls for healthcare initiatives to advance preventive and post-treatment strategies.

Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis.

BACKGROUND: Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent. OBJECTIVES: The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality. METHODS: The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes. RESULTS: Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15). CONCLUSIONS: Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626).

Metoprolol Improves Left Ventricular Longitudinal Strain at Rest and during Exercise in Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (HCM) often experience symptoms of heart failure upon exertion despite having normal left ventricular (LV) ejection fractions. Longitudinal strain (LS) may be a more sensitive marker of systolic dysfunction in patients with LV hypertrophy. The aims of this study were to characterize LV segmental LS and global LS (GLS) at rest and during exercise and to assess if first-line treatment with ß-blockers improves LV systolic performance. METHODS: Twenty-nine patients with obstructive HCM and New York Heart Association functional class ≥ II symptoms were enrolled in a double-blind, placebo-controlled, randomized crossover trial. Patients received metoprolol 150 mg or placebo for two consecutive 2-week periods in random order. Echocardiographic assessment with speckle-tracking-derived LS was performed at rest and during peak exercise at the end of each treatment period. RESULTS: During placebo treatment, resting values of segmental LS showed an apical-basal difference of -10.3% (95% CI, -12.7% to -7.8%; P < .0001), with a severely abnormal value of the basal segment of -9.3 ± 4.2%. Treatment with metoprolol was associated with more negative LS values of the apical segment (-2.8%; 95% CI, -4.2% to -1.3%; P < .001) and the mid segment (-1.1%; 95% CI, -2.0% to -0.3%; P = .007). During peak exercise there was a deterioration in LV GLS, but treatment with metoprolol was associated with more negative peak exercise LV GLS (-1.3 %; 95% CI, -2.6% to -0.1%; P = .03). CONCLUSIONS: Systolic performance assessed by LV GLS showed impaired values at rest and during exercise, with severely depressed values of the basal and mid segments. Treatment with metoprolol improved LV GLS upon exercise, indicating a beneficial effect of ß-blocker treatment on LV systolic function.

Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab.

AIMS: European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals <1.4 mmol/L after acute coronary syndrome (ACS), and <1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy. METHODS AND RESULTS: The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18 924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17 589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9-2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C <1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C <1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C <1.4 and <1.0 mmol/L in 10.6 and 0%, respectively, at baseline (assuming 18 ± 3% reduction of LDL-C). CONCLUSION: Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, the addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal <1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve <1.0 mmol/L. In contrast, the addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C <1.4 mmol/L in only 10.6% of patients at baseline.

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood. OBJECTIVES: This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM. METHODS: This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest. RESULTS: No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008). CONCLUSIONS: In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

[Trikuspidalklapinsufficiens].

Tricuspid regurgitation (TR) has in recent literature been described as an independently progressive disorder associated with a poor prognosis. Studies have emphasized the importance of a more proactive approach in treating TR in order to prevent progression of right ventricular dysfunction and ultimately right heart failure. These findings have renewed interest in surgical treatment for isolated TR whilst also fueling rapid advancements in transcatheter therapies, as argued in this review.

Subclinical leaflet thrombosis after transcatheter aortic valve implantation: no association with left ventricular reverse remodeling at 1-year follow-up.

Hypo-attenuated leaflet thickening (HALT) of transcatheter aortic valves is detected on multidetector computed tomography (MDCT) and reflects leaflet thrombosis. Whether HALT affects left ventricular (LV) reverse remodeling, a favorable effect of LV afterload reduction after transcatheter aortic valve implantation (TAVI) is unknown. The aim of this study was to examine the association of HALT after TAVI with LV reverse remodeling. In this multicenter case-control study, patients with HALT on MDCT were identified, and patients without HALT were propensity matched for valve type and size, LV ejection fraction (LVEF), sex, age and time of scan. LV dimensions and function were assessed by transthoracic echocardiography before and 12 months after TAVI. Clinical outcomes (stroke or transient ischemic attack, heart failure hospitalization, new-onset atrial fibrillation, all-cause mortality) were recorded. 106 patients (age 81 ± 7 years, 55% male) with MDCT performed 37 days [IQR 32-52] after TAVI were analyzed (53 patients with HALT and 53 matched controls). Before TAVI, all echocardiographic parameters were similar between the groups. At 12 months follow-up, patients with and without HALT showed a significant reduction in LV end-diastolic volume, LV end-systolic volume and LV mass index (from 125 ± 37 to 105 ± 46 g/m2, p = 0.001 and from 127 ± 35 to 101 ± 27 g/m2, p < 0.001, respectively, p for interaction = 0.48). Moreover, LVEF improved significantly in both groups. In addition, clinical outcomes were not statistically different. Improvement in LVEF and LV reverse remodeling at 12 months after TAVI were not limited by HALT.

Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: The use of ß-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies. OBJECTIVES: This study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM. METHODS: This double-blind, placebo-controlled, randomized crossover trial enrolled 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020. Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing. RESULTS: Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg [interquartile range (IQR): 15-58 mm Hg] vs 72 mm Hg [IQR: 28-87 mm Hg]; P = 0.007), at peak exercise (28 mm Hg [IQR: 18-40 mm Hg] vs 62 mm Hg [IQR: 31-113 mm Hg]; P < 0.001), and postexercise (45 mm Hg [IQR: 24-100 mm Hg] vs 115 mm Hg [IQR: 55-171 mm Hg]; P < 0.0001). During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide did not differ between the study arms. CONCLUSIONS: Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged. (The Effect of Metoprolol in Patients with Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

Coronary Flow Velocity Reserve and Myocardial Deformation Predict Long-Term Outcomes in Heart Transplant Recipients.

BACKGROUND: After heart transplantation (HTx), invasive coronary angiography is the gold standard for surveillance of cardiac allograft vasculopathy (CAV). Noninvasive CAV surveillance is desirable. The authors examined left ventricular global longitudinal strain (LVGLS) and noninvasive coronary flow velocity reserve (CFVR) related to CAV and prognosis after HTx. METHODS: Doppler echocardiographic CFVR and LVGLS were evaluated in 98 HTx patients. All-cause mortality and major adverse cardiac events (MACE), including hospitalization for heart failure, cardiovascular death, and significant CAV progression, were recorded. RESULTS: Median follow-up duration was 3.3 years (range: 1.7-5.4 years). Patients with low CFVR (<2.0; n = 20) showed reduced MACE-free survival (hazard ratio, 4.3; 95% CI, 2.2-8.4; P < .0001) and increased all-cause mortality (hazard ratio: 4.7; 95% CI: 2.0-11.3; P < .0001) compared with patients with high CFVR (≥2.0; n = 78). Worsened LVGLS (≥-15.5%) was also a strong independent predictor of MACE and cardiovascular and all-cause mortality. Combined low CFVR and worsened LVGLS provided incremental prognostic value, even after adjustment for CAV and time since HTx. The prevalence of low CFVR increased significantly with CAV severity, and the prevalence of combined low CFVR and/or worsened LVGLS was high in patients with moderate CAV (86%) and those with severe CAV (83%). The negative predictive value of combined high CFVR and improved LVGLS to rule out significant CAV was 94.5% (95% CI, 86.2%-98.4%), whereas the positive predictive value was 39.0% (95% CI, 25.3%-54.3%). The model had sensitivity of 84.2% (95% CI, 63.6%-95.3%) and specificity of 67.5% (95% CI, 56.6%-77.2%) for one or more abnormal parameters. CONCLUSIONS: In HTx patients with severe CAV, a higher prevalence of low CFVR and worsened LVGLS was observed. Both measurements were strong independent predictors of MACE and all-cause mortality in HTx patients. Combined CFVR and LVGLS provided incremental prognostic value and showed an excellent ability to rule out significant CAV and may be considered as part of routine CAV surveillance of HTx patients.

Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation.

OBJECTIVE: The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). BACKGROUND: Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. METHODS: Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. RESULTS: Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). CONCLUSIONS: AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.

Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study.

OBJECTIVES: Recent evidence suggests that patients with a corrected atrial septal defect (ASD) have higher morbidity and mortality. An abnormal autonomic regulation of the heart may be a part of the explanation for this. Our objective was to study heart rate variability (HRV) in adults with a corrected ASD as a prominent tool to investigate the autonomic regulation of the heart. METHODS: Autonomic cardiac function was investigated in adults with either a surgically closed or percutaneously closed ASD and healthy control subjects. A 48-h Holter monitor was performed on each participant and HRV was assessed. RESULTS: A total of 17 patients with surgically closed ASDs, 18 percutaneously closed ASDs and 18 controls were included. The mean age in the surgical group, percutaneous group and controls was 32 ± 9, 28 ± 7 and 32 ± 10 years, respectively. The mean time since closure was 19 ± 8 years for the surgical group and 15 ± 5 years for the percutaneous group. The surgically closed ASD patients showed decreased HRV in all six parameters studied when compared to the controls. Similarly, the percutaneously closed ASDs showed decreased HRV in three out of six parameters when compared to controls. CONCLUSIONS: Adults with an ASD, whether closed surgically or percutaneously, have impaired HRV compared to their age- and sex-matched controls, more so in the patients with a surgically closed ASD. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT03565471).

A systematic approach to weaning from extracorporeal membrane oxygenation in patients with refractory cardiac failure.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is commonly used to provide haemodynamic support for patients with severe cardiac failure. However, timing ECMO weaning remains challenging. We aimed to examine if an integrative weaning approach based on predefined haemodynamic, respiratory and echocardiographic criteria is associated with successful weaning. METHODS: All patients weaned from ECMO between April 2017 and April 2019 at Aarhus University Hospital, Denmark, were consecutively enrolled. Predefined haemodynamic, respiratory and echocardiographic criteria were assessed before and during ECMO flow reduction. A weaning attempt was commenced in haemodynamic stable patients and patients remaining stable at minimal flow were weaned from ECMO. Comparisons were made between patients who met the criteria for weaning at first attempt and patients who did not meet these criteria. Patients completing a full weaning attempt with no further need for mechanical support within 24 h were defined as successfully weaned. RESULTS: A total of 38 patients were included in the study, of whom 26 (68%) patients met the criteria for weaning. Among these patients, 25 (96%) could be successfully weaned. Successfully weaned patients were younger and had less need for inotropic support and ECMO duration was shorter. Fulfilling the weaning criteria was associated with successful weaning and both favourable 30-d survival and survival to discharge. CONCLUSION: An integrative weaning approach based on haemodynamic, respiratory and echocardiographic criteria may strengthen the clinical decision process in predicting successful weaning in patients receiving ECMO for refractory cardiac failure.

Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent.

OBJECTIVES: The aim of this study was to characterize the cardiovascular disease (CVD) profile and describe the incidence and characteristics of cardiovascular (CV) events in patients with esophageal cancer (EC) following chemoradiation and surgery. BACKGROUND: Underlying CVD is a concern in patients with EC receiving curative treatment with chemoradiation and surgery. METHODS: Consecutive patients with EC referred for curative treatment were enrolled. Clinical CVD status, ongoing CVD treatment, cardiac function, and physical performance were assessed before chemoradiation. During a 90-day follow-up period, all CV events were noted and classified after in-depth medical record review. CV events were defined by major adverse CV events (transient ischemic attack, imaging-verified new stroke, unstable angina, heart failure or cardiomyopathy) or by Common Terminology Criteria for Adverse Events grade ≥3 (arrhythmia, thromboembolic events, or pericardial effusion requiring pericardiocentesis). RESULTS: Among 55 patients enrolled (median age 67 years; range: 50-86 years; 89% men), 22% had CVD prior to chemoradiation, and 11% with pre-existing CVD were inadequately treated according to current CV guidelines. Thirteen patients (24%) developed 15 events during follow-up. Pre-existing atrial fibrillation and a dilated left atrium were significantly associated with subsequent CV events. Left ventricular (LV) systolic dysfunction was frequently noted; 51% had impaired LV global longitudinal strain (<18%), and 16% had LV ejection fraction <50%. CONCLUSIONS: A systematic cardiac evaluation prior to chemoradiation in patients with EC revealed a high prevalence of undetected CVD, inadequately treated pre-existing CVD, and a high incidence of CV events after chemoradiation. These findings highlight the need for a systematic baseline cardiac examination in patients with EC to optimize CVD treatment. (Impact of Cancer Therapy on Myocardial Function in Patients With Esophagus Cancer [Heartcheck]; NCT03619317).

Platelet aggregation and response to aspirin therapy in cardiac allograft vasculopathy.

BACKGROUND: Long-term survival after heart transplantation (HTx) is compromised by cardiac allograft vasculopathy (CAV) characterized by coronary macro- and microvascular disease. The pathogenesis of CAV is unclear and may involve coronary thrombosis. We investigated whether HTx patients with CAV had higher platelet aggregation and turnover than HTx patients without CAV and healthy controls. Furthermore, we investigated the anti-platelet effect of low-dose aspirin in HTx patients. METHODS: We included 57 patients who had undergone HTx (median 8.3 years from HTx) and 57 healthy controls. Platelet aggregation was measured on-aspirin and off-aspirin using impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA). We evaluated platelet turnover by flow cytometry, CAV burden by coronary angiography and echocardiography, and microvascular function by echocardiographic coronary flow velocity reserve (CFVR). RESULTS: Off-aspirin, HTx patients with CAV (n = 21) had higher ADP-induced platelet aggregation than healthy controls (p < 0.01) and HTx patients without CAV (n = 36) (p < 0.05). Aspirin treatment reduced AA-induced platelet aggregation in both HTx groups, but HTx patients with CAV had higher platelet aggregation on-aspirin than HTx patients without CAV (p < 0.05). Platelet turnover did not differ between HTx patients with CAV and HTx patients without CAV (p > 0.34). HTx patients with lower CFVR values had higher platelet aggregation than HTx patients with higher CFVR values (p < 0.05). CONCLUSIONS: Off-aspirin, platelet aggregation was higher in HTx patients with CAV than in HTx patients without CAV and healthy controls. On-aspirin, platelet aggregation was higher in HTx patients with CAV than in HTx patients without CAV. Aspirin monotherapy may not provide sufficient platelet inhibition in HTx patients with CAV.

A case report: metastasis of melanoma to the heart in an era of immunotherapy.

BACKGROUND: Cardiac metastasis of melanoma rarely causes heart failure symptoms and the recognition of cardiac involvement is in most cases first established post-mortem. Surgical removal might be considered in selected cases in patients with an inflow or outflow tract obstruction even though the survival remains poor. Frequently, the metastasis cannot be removed and therapeutic options include conventional chemotherapy or immunotherapy, which is currently recommended as first-line treatment. Since the introduction of immunotherapy survival in metastatic disease has significantly increased but data on patients treated for melanoma with cardiac involvement are scarce. CASE SUMMARY: A 65-year-old man presented with dyspnoea and fatigue. Computed tomography scan revealed tumour processes in the heart, which was confirmed on echocardiography. Biopsies taken from fluorodeoxyglucose positron emission tomography positive lymph nodes in the axilla and groin showed melanoma. Analyses did not reveal BRAF mutation and the PD-L1 expression in tumour cells was below 1%. Treatment with ipilimumab and nivolumab was initiated and cardiopulmonary symptoms subsided during the following months with significant reduction in cardiac metastasis on echocardiography. Unfortunately, the patient developed immune checkpoint inhibitor-induced colitis and could no longer continue on the therapy. Due to development of extra-cardiac and cerebral metastasis, he was referred to palliative care. DISCUSSION: This case demonstrates that timely treatment with immunotherapy could be a safe and effective option for melanoma with cardiac involvement. During treatment, the patient developed severe colitis, a known side effect to immunotherapy. Though this often can be managed with steroids it complicates further treatment.

Survival, graft function, and incidence of allograft vasculopathy in heart transplant patients receiving adverse risk profile donor hearts.

AIM: To clarify if use of adverse cardiovascular risk profile (ARP) grafts is associated with impaired long-term outcomes after heart transplantation (HTx). METHODS: Survival was obtained from Scandia Transplant and a local database. ARP DONOR INCLUSION CRITERIA: ≥55 years, diabetes mellitus, arterial hypertension, hypoxemia-induced death, impaired left ventricular (LV) ejection fraction. ARP donors were compared to donors not meeting the eligibility criteria. Sub-analyses were made for donor age. RESULTS: In total, 302 HTxs were performed in 296 patients from 31 December 1992 to 11 August 2016. Median survival was 16.5 years (95% CI, 14.3-22.9), there was no difference between profiles (HR 0.63 (95% CI, 0.33-1.19), P = 0.15). LV systolic function was significantly better in ARP donors (P < 0.05). Freedom from cardiac allograft vasculopathy (CAV) was comparable between profiles, HR 0.9 (95% CI 0.5-1.5). Donor age predisposes to CAV (high to low age: HR 2.8 (95% CI 1.7-4.5), P < 0.0001). Median survival was comparable in patients receiving allograft ≥55 and <55 years (HR 0.77 (95% CI 0.4-1.4), P = 0.38). CONCLUSION: Long-term survival and graft function were excellent in patients receiving ARP grafts. Older grafts were associated with CAV but did not influence survival. Thus, the strategy of expanding availability using ARP grafts seems safe.

Diagnostic value of layer-specific global longitudinal strain during adenosine stress in patients suspected of coronary artery disease.

Speckle tracking global longitudinal strain (GLS) from dobutamine stress echocardiography (SE) predicts coronary artery disease (CAD). The diagnostic value of GLS from vasodilator SE and the additional value of layer-specific speckle tracking analysis are unclear. We explored the usefulness of layer-specific GLS and non-layer-specific strain (automated functional imaging, AFI) from adenosine SE. The included 132 patients (67% male, 62.6 (9.0) years), of which 46 (35%) had CAD defined as ≥1 stenosis ≥70% (≥50% in the left main), underwent adenosine SE and invasive coronary angiography. Resting AFI and layer-specific GLS were similar in patients with or without CAD (p > 0.05). The stress-rest difference (Δvalue = stress-value - rest-value) in patients with CAD was less pronounced compared to patients without proved CAD (Δendocardial GLS: -1.2 (3.5)% vs. -5.0 (3.2)%; Δmidventricular GLS: -0.95 (3.0)% vs. -4.2 (2.7)%; Δepicardial GLS: -0.7 (2.5)% vs. -3.4 (2.3)%; ΔAFI: -0.8 (2.9)% vs. -3.6 (3.1)%, p < 0.00001 for all comparisons). The diagnostic value of the three layer-specific GLS values and AFI were statistically similar (p = 0.19). The four Δvalues provided independent predictive value to the risk assessment given by gender, age, wall motion and ΔEF (p = 0.002, AFI and p < 0.0001, layer-specific GLS). The accuracies were acceptable (71-80%) with modest sensitivities (54-65%) and high specificities (80-91%). The deformation response to vasodilator infusion was associated with the presence of CAD. Endocardial, midventricular and epicardial GLS and AFI from adenosine SE had similar diagnostic values. The specificities were high, but the modest sensitivities are a limitation to the clinical application.

A rare presentation of cardiac amyloid deposits isolated to intramural vessels.

The present case illustrates the diagnostic challenges in symptomatic patients with heart failure of unknown etiology. The patients were previously diagnosed with κ-light chain amyloidosis without cardiac involvement. Echocardiography showed heart failure with mildly reduced ejection fraction but no signs of amyloidosis. Coronary angiogram showed normal arteries and 11C-PIB positron emission tomography was negative for amyloid deposits. Exercise testing revealed severe heart failure and reduced coronary flow velocity reserve. Endomyocardial biopsies showed amyloid in the intramural coronary arteries without interstitial amyloid deposits. Hence, the patient was diagnosed with microvascular dysfunction-induced heart failure due to vessel wall amyloidosis.

Transcatheter Aortic Valve Thrombosis: Incidence, Predisposing Factors, and Clinical Implications.

BACKGROUND: There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR. METHODS: Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis. RESULTS: MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT. CONCLUSIONS: Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications.