Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Association between heart failure and the incidence of cancer: a systematic review and meta-analysis.

Aims: The association between heart failure (HF) patients and the incidence of cancer is not well understood, with conflicting results to date. The aim of this meta-analysis was to evaluate whether patients with HF have a higher risk of developing cancer. Methods and results: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10 December 2022. The primary clinical outcome was the incidence of cancer. Secondary endpoints were the incidence of breast cancer, lung cancer, haematological cancer, colorectal cancer, and prostate cancer. A total of 9 articles with 7 329 706 (515 041 HF vs. 6 814 665 non-HF) patients were involved in the analysis. The mean age of the patients in the HF and the non-HF groups was 69.06 and 66.76 years. The median follow-up duration was 6.7 years. The most common comorbidity among both groups includes diabetes mellitus (27.58 vs. 14.49%) and hypertension (81.46 vs. 57.38%). Patients with HF were associated with a significant increase in the incidence of cancer {hazard ratio [HR], 1.43 [95% confidence interval (CI): 1.21-1.68], P < 0.001}, breast cancer [HR, 1.28 (95% CI: 1.09-1.50), P < 0.001], lung cancer [HR, 1.89 (95% CI: 1.25-2.85), P < 0.001], haematological cancer [HR, 1.63 (95% CI: 1.15-2.33), P = 0.01], and colorectal cancer [HR, 1.32 (95% CI: 1.11-1.57), P < 0.001] compared with patients without HF. However, the incidence of prostate cancer was comparable between both groups [HR, 0.97 (95% CI: 0.66-1.43), P = 0.88]. Conclusion: This meta-analysis confirms that the state of HF is associated with a higher risk for incident cancer. These data may aid in raising awareness with physicians that cancer may develop in patients with prevalent heart failure and that early screening and evaluation may be useful in an early diagnosis of cancer.

Differential Diagnosis of Diarrhea in Patients With Neuroendocrine Tumors.

Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience diarrhea that can have a debilitating effect on quality of life. Diarrhea also may develop in response to other hormonal syndromes associated with NETs, surgical complications, medical comorbidities, medications, or food sensitivities. Limited guidance on the practical approach to the differential diagnosis of diarrhea in these patients can lead to delays in appropriate treatment. This clinical review and commentary underscore the complexity in identifying the etiology of diarrhea in patients with NETs. Based on our collective experience and expertise, we offer a practical algorithm to guide medical oncologists and other care providers to expedite effective management of diarrhea and related symptoms in patients with NETs.

Burden of Carcinoid Heart Disease in Patients With Carcinoid Syndrome Initiating Somatostatin Analogues.

PURPOSE: As a result of overproduction of serotonin, patients with uncontrolled carcinoid syndrome (CS) may develop carcinoid heart disease (CaHD). However, the prevalence and health care resources to manage CaHD are not well understood. This study investigated the prevalence and economic burden of CaHD among adults with CS in the United States. METHODS: This retrospective study analyzed insurance claims of patients with CS initiating somatostatin analogue (SSA) therapy. Eligible patients had ≥1 medical claim for CS with continuous insurance coverage for 1 year before and at least 30 days after initiating SSA therapy. Markers for CaHD were identified using a predetermined list of medical and/or procedural claims based on the clinical experience of a practicing cardiologist. Case subjects had a documented medical/procedural claim for a marker of CaHD during the study period; control subjects had no markers for CaHD. Baseline characteristics were assessed during the pre-SSA treatment initiation period. Economic outcomes (health care resources and expenditures) were assessed in the follow-up period after SSA treatment initiation and compared between incident case subjects and control subjects. Descriptive statistics were used to assess demographic and clinical characteristics. Univariate and multivariate models were used to assess differences in health care resource use and costs between case subjects and control subjects. FINDINGS: A total of 654 patients met the eligibility criteria; 248 (38%) had a prevalent marker of CaHD and were excluded from the economic analysis. The analytic sample included 406 patients with CS, 185 (46%) of whom had an incident CaHD marker (case subjects) and 221 were controls. Baseline characteristics between the case subjects and control subjects were similar with the exception that case subjects tended to be older. Average health care resource use and costs were higher among case subjects (total costs, $51,825 vs $29,068; P < 0.01), driven by average hospital admissions (1.4 vs 0.7) with increased length of stay (4.3 vs 2.0 days), office visits (22.8 vs 19.8), and outpatient services (22.3 vs 15.4; all, P < 0.05). IMPLICATIONS: CaHD may be common among patients with CS before initiating SSA therapy and within 2 years of starting SSA therapy, suggesting suboptimal control of serotonin production. Patients with CaHD incur substantial economic costs in addition to the clinical morbidity compared with patients with CS and no CaHD.

Serotonin levels and 1-year mortality in patients with neuroendocrine tumors: a systematic review and meta-analysis.

Aim: Elevated serotonin in patients with neuroendocrine tumors (NETs) may impact heart failure incidence but a quantitative relationship has not been established. Materials & methods: Systematic review and meta-analysis of studies assessing 24-h urinary 5-hydroxyindoleacetic acid (u5-HIAA) and mortality in patients with NETs (2007-2017) with a primary outcome of 1-year mortality risk and 24-h u5-HIAA. Results: We identified 1715 records of which 12 studies including 755 patients (3442 person-years with 376 deaths) were eligible for meta-analysis. Mean u5-HIAA was 149.2 mg/24 h (standard deviation: 96.6) and mortality was 13.0%. The meta-regression equation showed an 11.8% (95% CI: 8.9-17.0%; I2  = 93.0%) increase in 1-year mortality for every ten-unit increase in u5-HIAA. Conclusion: Serotonin measured by its metabolite u5-HIAA is predictive of 1-year all-cause mortality in patients with NETs.

Echocardiography in functional midgut neuroendocrine tumors: When and how often.

The management of patients with midgut neuroendocrine tumors (MNET) is rapidly evolving. Current preoperative detection rates of primary tumor sites are higher than ever and progression-free survival in patients with already advanced disease is expanding due to the implementation of novel efficacious treatment strategies. This survival benefit may potentially translate into a need for a multidisciplinary approach to an even more heterogenous variety of clinical conditions, among these, carcinoid syndrome (CS) and carcinoid heart disease (CHD). The latter often triggers substantial morbidity and mortality, hence a systematic screening, an accurate diagnosis, as well as effective interventions are critically important. The rarity of the disease has result in a relative lack of statistically powerful evidence, which in turn may have rendered significant variability between practices. In this regard, despite recent guidelines, the optimal follow-up of patients with CHD remain debatable to some authors, perhaps due to the preponderance of certain schools throughout the manuscript. Herein, we present a concise and practical guidance document on clinical screening and echocardiographic surveillance of patients with CHD based on a comprehensive review of the literature, and complemented by our experience at the Center for Carcinoid and Neuroendocrine Tumors at The Mount Sinai Hospital.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors.

There have been significant developments in diagnostic and therapeutic options for patients with neuroendocrine tumors (NETs). Key phase 3 studies include the CLARINET trial, which evaluated lanreotide in patients with nonfunctioning enteropancreatic NETs; the RADIANT-2 and RADIANT-4 studies, which evaluated everolimus in functioning and nonfunctioning NETs of the gastrointestinal tract and lungs; the TELESTAR study, which evaluated telotristat ethyl in patients with refractory carcinoid syndrome; and the NETTER-1 trial, which evaluated Lu-DOTATATE in NETs of the small intestine and proximal colon (midgut). Based on these and other advances, the North American Neuroendocrine Tumor Society convened a multidisciplinary panel of experts with the goal of updating consensus-based guidelines for evaluation and treatment of midgut NETs. The medical aspects of these guidelines (focusing on systemic treatment, nonsurgical liver-directed therapy, and postoperative surveillance) are summarized in this article. Surgical guidelines are described in a companion article.

Diagnosing and Managing Carcinoid Heart Disease in Patients With Neuroendocrine Tumors: An Expert Statement.

Carcinoid heart disease is a frequent occurrence in patients with carcinoid syndrome and is responsible for substantial morbidity and mortality. The pathophysiology of carcinoid heart disease is poorly understood; however, chronic exposure to excessive circulating serotonin is considered one of the most important contributing factors. Despite recognition, international consensus guidelines specifically addressing the diagnosis and management of carcinoid heart disease are lacking. Furthermore, there is considerable variation in multiple aspects of screening and management of the disease. The aim of these guidelines was to provide succinct, practical advice on the diagnosis and management of carcinoid heart disease as well as its surveillance. Recommendations and proposed algorithms for the investigation, screening, and management have been developed based on an evidence-based review of the published data and on the expert opinion of a multidisciplinary consensus panel consisting of neuroendocrine tumor experts, including oncologists, gastroenterologists, and endocrinologists, in conjunction with cardiologists and cardiothoracic surgeons.

Carcinoid Heart Disease without Liver Involvement Caused by a Primary Ovarian Carcinoid Tumour.

Carcinoid heart disease, caused by primary ovarian carcinoid tumour, is a rare form of valvular heart disease. This form of heart disease usually presents with symptoms of right-sided valvular dysfunction, ultimately leading to right-sided heart failure. This entity is unique as it develops in the absence of liver metastasis. We report a case of 75 year-old woman with primary ovarian carcinoid tumour who presented with symptoms of severe right-sided heart failure and successfully underwent pulmonic and tricuspid valve replacement along with a right ventricular (RV) outflow patch enlargement. This patient later underwent uneventful resection of the primary ovarian carcinoid tumour, with complete resolution of her symptoms.

An Analysis of Global Research Trends in Cardiology Over the Last two Decades.

INTRODUCTION: Heart disease today is a major cause of morbidity and mortality plaguing mankind worldwide. AIM: The present research was undertaken to ascertain global research trends in clinical trials in Cardiology involving human subjects over the last two decades. MATERIALS AND METHODS: Cross-sectional study. A detailed search strategy was employed in December 2013, using the PubMed database. All papers published in 1993-2013 were evaluated. The research trends of various cardiologic subspecialties in the United States and worldwide have been analysed and detailed statistical analysis was done. RESULTS: United States had maximum number of researches. Clinical trials involving infarction were maximum followed by coronary angiography and coronary angioplasty in that order. The year 2013 had the most researches. The United States was the top country and Boston was the top city. Author Christodoulos Stefanadis had the greatest number of researches in this field. American Journal of Cardiology was the most favored journal and Circulation was the journal with the highest impact factor. This effort may help funding agencies, prospective job seekers, fellowship applicants, policymakers and patients Conclusion: The research output in cardiology has increased and improved significantly over past decade. The publication per diplomat is more in transplant cardiology, Also more clinical trials involving coronary restenosis have to be done to know in depth to add to current knowledge and database.

Percutaneous closure of a patent foramen ovale in left-sided carcinoid heart disease.

BACKGROUND: A 51-year-old woman with a 5-year history of metastatic small bowel carcinoid disease developed fatigue and gradually worsening dyspnea on exertion, over 6 months. INVESTIGATIONS: Physical examination, transthoracic and transesophageal echocardiography, and aortography. DIAGNOSIS: Left-sided carcinoid disease associated with a patent foramen ovale. MANAGEMENT: Percutaneous transcatheter closure of the patent foramen ovale.