ABSTRACT
BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.
Subject(s)
Anticoagulants , Heart Transplantation , Humans , Anticoagulants/adverse effects , Retrospective Studies , Warfarin/adverse effects , Biopsy , Hemorrhage , Heart Transplantation/adverse effectsABSTRACT
BACKGROUND: Deposition of wild-type or mutant transthyretin (TTR) amyloid fibrils in the myocardium causes TTR amyloid cardiomyopathy (ATTR-CM). Targeted therapeutics for ATTR-CM include TTR stabilizers (tafamidis and diflunisal) and oligonucleotide drugs (revusiran, patisiran, and inotersen). TTR stabilizers prevent dissociation of transthyretin tetramers. Transthyretin monomers can misfold and form amyloid fibrils. TTR stabilizers thereby limit amyloid fibrils development and deposition. Oligonucleotide drugs inhibit hepatic synthesis of transthyretin, which decreases transthyretin protein levels and thus the amyloid fibril substrate. AREAS OF UNCERTAINTY: To study the safety and efficacy of targeted therapeutics in patients with ATTR-CM, we performed a pooled analysis. A random-effects model with the Mantel-Haenszel method was used to pool the data. DATA SOURCES: A literature search was performed using PubMed, Cochrane CENTRAL, and Embase databases using the search terms "cardiac amyloidosis" AND "tafamidis" OR "patisiran" OR "inotersen" OR "revusiran" OR "diflunisal." THERAPEUTIC ADVANCES: We identified 6 studies that compared targeted therapeutics with placebo. One study was stopped prematurely because of increased mortality in the targeted therapeutics arm. Pooled analysis included 1238 patients, of which 738 patients received targeted therapeutics and 500 patients received placebo. When compared with placebo, targeted therapeutics significantly reduced all-cause mortality [OR 0.39, 95% confidence interval (CI): 0.16-0.97, P = 0.04]. Only 2 studies reported the effect on cardiovascular-related hospitalizations. There was a trend toward an improvement in global longitudinal strain (mean difference -0.69, 95% CI: -1.44 to 0.05, P = 0.07). When compared with placebo, there was no increase in serious adverse events with targeted therapeutics (OR 1.06, 95% CI: 0.78-1.44, P = 0.72). CONCLUSION: Evidence from the pooled analysis revealed targeted therapeutics improve survival and are well-tolerated. These findings suggest a potential role for targeted therapeutics in the treatment of patients with ATTR-CM.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Diflunisal , Humans , Amyloid Neuropathies, Familial/drug therapy , Prealbumin/metabolism , Prealbumin/therapeutic use , Diflunisal/pharmacology , Diflunisal/therapeutic use , Oligonucleotides/pharmacology , Oligonucleotides/therapeutic use , Cardiomyopathies/drug therapyABSTRACT
There is limited evidence comparing direct oral anticoagulants (DOACs) and warfarin in solid organ transplant (SOT) recipients. We performed a pooled analysis to study the safety and efficacy of DOACs in this patient population. We searched PubMed, Embase, and Scopus databases using the search terms "heart transplant" or "lung transplant" or "liver transplant" or "kidney transplant" or "pancreas transplant" and "direct oral anticoagulant" for literature search. Random effects model with Mantel-Haenszel method was used to pool the outcomes. Pooled analysis included 489 patients, of which 259 patients received DOACs and 230 patients received warfarin. When compared to warfarin, the use of DOACs was associated with decreased risk of composite bleed (RR .49, 95% CI .32-.76, p = .002). There were no differences in rates of major bleeding (RR .55, 95% CI .20-1.49, p = .24) or venous thromboembolism (RR .65, 95% CI .25-1.70, p = .38) between the two groups. Evidence from pooled analysis suggests that DOACs are comparable to warfarin in terms of safety in SOT recipients. Further research is warranted to conclusively determine whether DOACs are safe alternatives to warfarin for anticoagulation in SOT recipients.
Subject(s)
Kidney Transplantation , Venous Thromboembolism , Administration, Oral , Anticoagulants/therapeutic use , Hemorrhage/etiology , Humans , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Warfarin/therapeutic useABSTRACT
BACKGROUND: Severe secondary mitral regurgitation (MR) is associated with poor prognosis in heart failure patients with left ventricular systolic dysfunction. Few observational and randomized controlled studies demonstrated the efficacy of transcatheter mitral valve repair in heart failure patients with significant MR. A meta-analysis of published studies was performed to evaluate the role of transcatheter mitral valve repair using the MitraClip device in heart failure patients with significant secondary MR. METHODS: A literature search was performed using PubMed, Cochran CENTRAL, and Embase databases using the search terms "percutaneous mitral valve repair" or "transcatheter mitral valve repair" and "heart failure." Studies that compared medical therapy plus transcatheter mitral valve repair using MitraClip to medical therapy alone in heart failure patients with significant secondary MR were included for pooled analysis. A random-effects model with the Mantel-Haenszel method was used to analyze the data. RESULTS: Four studies, 2 randomized controlled and 2 nonrandomized studies met the criteria for analysis. Pooled analysis included a total of 1,421 patients, of which 746 patients underwent transcatheter mitral valve repair and 675 patients received medical therapy alone. When compared to medical therapy, transcatheter mitral valve repair significantly decreased all-cause mortality (OR 0.58, 95% CI 0.37-0.91; p = 0.02). A trend toward significant reduction in rehospitalizations (OR 0.35, 95% CI 0.12-1.00; p = 0.05) was also observed. Periprocedural complications ranged from 7.5 to 12.6%. CONCLUSION: Evidence from pooled analysis suggests that transcatheter mitral valve repair using MitraClip on top of medical therapy, in appropriately selected symptomatic heart failure patients with significant secondary MR, provides survival benefit and may decrease hospitalizations when compared with guideline-directed medical therapy alone.
Subject(s)
Heart Failure , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Cardiac Catheterization , Heart Failure/surgery , Humans , Mitral Valve/surgery , Mitral Valve Insufficiency/surgery , Treatment OutcomeABSTRACT
OPINION STATEMENT: Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Cardiovascular Diseases/epidemiology , Prostatic Neoplasms/drug therapy , Androstenes/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , COVID-19/epidemiology , COVID-19/pathology , Cardiotoxicity , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/ethnology , Disease Susceptibility , Gonadotropin-Releasing Hormone/agonists , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Health Status Disparities , Humans , Male , Prostatic Neoplasms/ethnology , SARS-CoV-2ABSTRACT
PURPOSE OF REVIEW: Radiation-induced cardiovascular disease, including coronary artery disease, is a well-known sequela of radiation therapy and represents a significant source of morbidity and mortality for cancer survivors. This review examines current literature and guidelines to care for this growing population of cancer survivors. RECENT FINDINGS: The development of radiation-induced ischemic heart disease following radiation can lead even to early cardiotoxicities, inclusive of coronary artery disease, which limit cancer treatment outcomes. These coronary lesions tend to be diffuse, complex, and proximal. Early detection with multimodality imaging and targeted intervention is required to minimize these risks. Early awareness, detection, and management of radiation-induced cardiovascular disease are paramount as cancer survivorship continues to grow.
Subject(s)
Cardiovascular Diseases , Myocardial Ischemia , Neoplasms , Cardiotoxicity , Cardiovascular Diseases/etiology , Early Detection of Cancer , Humans , Myocardial Ischemia/etiology , Neoplasms/radiotherapy , Radiotherapy/adverse effectsABSTRACT
PURPOSE OF REVIEW: Cancer treatment-related cardiotoxicity (CTRC) represents a significant cause of morbidity and mortality worldwide. The purpose of our review is to summarize the epidemiology, natural history, and pathophysiology of cardiotoxicity-related to cancer treatment. We also summarize appropriate screening, surveillance, and management of CTRC. While cardiotoxicity is characteristically associated with anthracyclines, HER2-B antagonists, and radiation therapy (XRT), there is growing recognition of toxicity with immune checkpoint inhibitors (ICI), tyrosine kinase inhibitors, and proteasome inhibitors. RECENT FINDINGS: Patients at risk for cardiotoxicity should be screened based on available guidelines, generally with serial echocardiograms. The role of medical heart failure (HF) therapies is controversial in patients with asymptomatic left ventricular dysfunction but may be considered in some instances. Once symptomatic HF has developed, treatment should be in accordance with ACC/AHA guidelines. The goal in caring for patients receiving cancer treatment is to optimize cardiac function and prevent interruptions in potentially lifesaving cancer treatment.
Subject(s)
Antineoplastic Agents/adverse effects , Cardiomyopathies/prevention & control , Cardiotoxicity/prevention & control , Neoplasms/drug therapy , Ventricular Function, Left/drug effects , Antineoplastic Agents/therapeutic use , Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Echocardiography , Humans , Risk FactorsABSTRACT
Improvements in detection and treatment of cancer have resulted in a significant increase in cancer survivors. However, cancer survivorship comes with long-term risk of adverse effects of cancer therapies, including cardiomyopathy, heart failure, arrhythmias, ischemic heart disease, atherosclerosis, thrombosis, and hypertension. There is a renewed interest in understanding the pathophysiology of cancer therapeuticserelated cardiac dysfunction. In recent years, efforts have been directed to the management of cancer therapeuticserelated cardiac dysfunction. This article discusses the pathophysiology and molecular mechanisms that contribute to cancer therapeutics-related cardiac dysfunction and presents an napproach to the evaluation and treatment of these patients.
Subject(s)
Antineoplastic Agents/adverse effects , Cardiomyopathies , Disease Management , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Cardiotoxicity , HumansABSTRACT
OBJECTIVE: To evaluate the long term efficacy and safety of long duration DAPT (L-DAPT) compared to short duration DAPT (S-DAPT) after drug-eluting stent (DES) implantation. METHODS: We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the clinical impact of L-DAPT versus S-DAPT after DES and have mean follow up period of at least 2 years or longer. Primary end point was stent thrombosis (ST). Secondary endpoints were all-cause mortality, cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR), thrombolysis in myocardial infarction (TIMI) major bleeding and stroke. Event rates were compared using a random effects model. RESULTS: We identified five RCTs in which 19,760 patients were randomized to S-DAPT (N = 9,810) and L-DAPT (n = 9,950), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of MI (odds ratio [OR] 1.48, 95% confidence interval [CI] [1.04, 2.10]). There were no significant differences between S-DAPT and L-DAPT in terms of all cause mortality, cardiac mortality, ST, TVR or stroke (OR 0.90, 95% CI [0.73, 1.12]; OR 1.02, 95% CI [0.80, 1.30]; OR 1.59, 95% CI [0.77, 3.27]; OR 0.87 95% CI [0.67, 1.14]; and OR 1.08 95% CI [0.81, 1.46], respectively). However, rate of TIMI major bleeding was significantly lower with S-DAPT compared to L-DAPT (OR 0.64, 95% CI [0.41, 0.99]). CONCLUSIONS: In the present analysis of RCTs with longer follow up (2 years or longer), S-DAPT compared with L-DAPT, was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all cause mortality, cardiac mortality, ST, TVR, and stroke.
Subject(s)
Coronary Artery Disease/therapy , Coronary Thrombosis/prevention & control , Drug-Eluting Stents , Percutaneous Coronary Intervention/instrumentation , Platelet Aggregation Inhibitors/administration & dosage , Aged , Chi-Square Distribution , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Thrombosis/diagnostic imaging , Coronary Thrombosis/etiology , Coronary Thrombosis/mortality , Drug Administration Schedule , Drug Therapy, Combination , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/prevention & control , Odds Ratio , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Platelet Aggregation Inhibitors/adverse effects , Randomized Controlled Trials as Topic , Risk Factors , Stroke/etiology , Stroke/prevention & control , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The Lariat procedure is increasingly used for the exclusion of the left atrial appendage (LAA) in atrial fibrillation (AF) patients. There are anecdotal reports of pleural effusions after the Lariat procedure. However, the incidence, demographics, and pathophysiology of these effusions are largely unknown. OBJECTIVE: Characterization of pleural effusions in patients who underwent LAA exclusion using the Lariat procedure. METHODS: We report the incidence, demographics, and clinical and laboratory characteristics of patients from a multicenter prospective registry who underwent the Lariat procedure and subsequently developed pleural effusions. RESULTS: A total of 10 out of 310 (3.2%) patients developed significant pleural effusions after the Lariat procedure. The mean age of these patients was 67 ± 9, ranging from 52 to 78 years and included 5 (50%) males. Nine patients had persistent AF with median CHADS2 score of 2.7 ± 1.2. The LAA was successfully ligated in all these patients. Post-Lariat procedure, 6 patients developed bilateral and 4 patients developed left-sided pleural effusions. Pleural tap revealed transudative in 2 and exudative in 6 patients. The remaining 2 patients responded to active diuresis and behaved clinically like transudative effusions. There is a statistically significant difference between the onset of pleural effusion after the Lariat procedure between tPLE versus ePLE groups (14 ± 1.2 vs. 6 ± 6, P = 0.05). CONCLUSION: Incidence of clinically significant pleural effusion is uncommon after the Lariat procedure and can be either exudative or transudative in nature depending on the underlying mechanisms. More prospective studies are needed to study the pathophysiologic basis of development of pleural effusions after the Lariat procedure.
Subject(s)
Atrial Appendage/surgery , Atrial Fibrillation/surgery , Cardiac Surgical Procedures/adverse effects , Pleural Effusion/epidemiology , Aged , Atrial Appendage/physiopathology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Exudates and Transudates , Female , Humans , Incidence , Ligation , Male , Middle Aged , Pleural Effusion/diagnosis , Pleural Effusion/physiopathology , Pleural Effusion/therapy , Prospective Studies , Registries , Risk Factors , Treatment Outcome , United States/epidemiologyABSTRACT
BACKGROUND: Pulmonary vein isolation (PVI) of the remnant pulmonary vein (PV) stumps in pneumonectomy patients has not been well characterized. METHODS: This is a multicenter observational study of patients with a remnant PV stump after pneumonectomy. Consecutive patients with a history of pneumonectomy and who had undergone RF ablation for drug refractory AF were identified from the AF database at the participating institutions. RESULTS: There were 15 patients in whom pneumonectomy was performed, for resection of tumors in 10, infection in 4, and bullae in 1 patient and who underwent RF ablation for AF. The mean age was 63 ± 7 years. The stumps were from the right lower PV in 5, left upper PV in 5, left lower PV in 3, and right upper PV in 2 patients. All the PV stumps were electrically active with PV potentials and 9 (60%) of them had triggered activity. PVI was performed in 14 and focal isolation in 1 patient. At 1-year follow-up, 80% were free of AF, off of antiarrhythmic medications. CONCLUSION: PV stumps in AF patients with previous pneumonectomy are electrically active and are frequently the sites of active firing. Isolation of these PV stumps can be accomplished safely and effectively using catheter ablation with no practical concern for PV stenosis or compromising PV stump integrity.
Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/methods , Pneumonectomy/adverse effects , Pulmonary Veins/surgery , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Catheter Ablation/adverse effects , Electrophysiologic Techniques, Cardiac , Feasibility Studies , Female , Humans , Male , Middle Aged , Phlebography/methods , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/physiopathology , Radiography, Interventional , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , United StatesABSTRACT
AIMS: Pocket haematoma is a common complication following pacemaker implantation. Impact of this complication on post-procedural outcomes has previously not been systematically studied. We sought to identify the incidence of pocket haematoma after a de novo pacemaker and cardiac resynchronization therapy (CRT) device implantation and evaluate its impact on the hospital outcomes using a large all-payer national inpatient database. METHODS AND RESULTS: Data from Nationwide Inpatient Sample 2010 was queried to identify all primary implantations of single chamber, dual chamber pacemakers, and biventricular devices during the year 2010 using the appropriate ICD-9 codes. Patients who experienced a procedure-related haematoma during the hospital stay were identified. Of a total of 78,751 primary pacemaker implantations in the year 2010, 1677 (2.1%) of the implantations were complicated by a pocket haematoma. Higher age groups, more complex pacemaker types (BiV > dual chamber > single chamber), and comorbidities such as congestive heart failure and coagulopathy were associated with an increased risk of pocket haematoma formation post-pacemaker implantation. Patients who developed a pocket haematoma had a longer length of stay (8.7 vs. 4.8 days, P < 0.001), higher hospitalization costs ($48,815 vs. $34,324, P < 0.001) and higher in-hospital mortality (2.0 vs. 0.7%, P < 0.001) compared with patients who did not develop a haematoma. CONCLUSIONS: Haematoma is a relatively common complication associated with pacemaker implantation; however, it adversely impacts in-hospital outcomes.
Subject(s)
Cardiac Resynchronization Therapy Devices/adverse effects , Cardiac Resynchronization Therapy/economics , Hematoma/epidemiology , Hospital Costs , Hospital Mortality , Length of Stay/economics , Postoperative Complications , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Comorbidity , Databases, Factual , Female , Humans , Infant , International Classification of Diseases , Male , Middle Aged , Multivariate Analysis , Regression Analysis , Sex Distribution , United States/epidemiology , Young AdultABSTRACT
Aliskiren, a direct renin inhibitor, is a novel antihypertensive agent with placebo-like tolerability. The patient developed acute renal failure after addition of aliskiren to combination of diuretic, angiotensin-converting enzyme inhibitor and aldosterone antagonist. This case highlights the point that acute renal failure can occur as an adverse effect of aliskiren. Because there is no conclusive evidence about the safety of aliskiren when used in combination with multiple drugs that inhibit renin angiotensin aldosterone system, caution should be exercised while initiating this drug in patients already on combination of diuretic, angiotensin-converting enzyme inhibitor and aldosterone antagonist.
Subject(s)
Acute Kidney Injury/chemically induced , Amides/adverse effects , Fumarates/adverse effects , Renin/antagonists & inhibitors , Aged , Amides/administration & dosage , Amides/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Diuretics/administration & dosage , Drug Therapy, Combination , Fumarates/administration & dosage , Fumarates/therapeutic use , Humans , Hypertension/drug therapy , Male , Mineralocorticoid Receptor Antagonists/administration & dosageABSTRACT
Atrial fibrillation (AF) is a very common tachyarrhythmia and is becoming increasingly prevalent, while dementia is a neurological condition manifested as loss of memory and cognitive ability. Both these conditions share several common risk factors. It is becoming increasingly evident that AF increases the risk of dementia. There are several pathophysiological mechanisms by which AF can cause dementia. AF increases the stroke risk and strokes are strongly associated with dementia. Besides stroke, altered cerebral blood flow in AF and cerebral microbleeds from anticoagulation may enhance the risk of dementia. Maintaining sinus rhythm may therefore decrease this risk. Catheter ablation is emerging as an effective alternative to maintain patients in sinus rhythm. This procedure has also shown promise in decreasing the risk of all types of dementia. Besides maintaining sinus rhythm and oral anticoagulation, aggressive risk factor modification may reduce the likelihood or delay the onset of dementia.
Subject(s)
Atrial Fibrillation/psychology , Dementia/etiology , Atrial Fibrillation/surgery , Catheter Ablation/methods , Dementia/prevention & control , Humans , Risk Assessment/methods , Stroke/etiology , Stroke/prevention & controlABSTRACT
Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24-0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76-1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41-4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.
ABSTRACT
Dronedarone is a relatively new antiarrhythmic drug approved for paroxysmal or persistent atrial fibrillation. Dronedarone can inhibit P-glycoprotein-mediated digoxin clearance and increase steady-state digoxin level 2.5 times. It is important to closely monitor plasma digoxin levels or administer a lower loading dose of digoxin in patients taking dronedarone concomitantly. We report a case of digoxin toxicity in a patient taking concomitant dronedarone as a result of interaction between digoxin and dronedarone.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Amiodarone/analogs & derivatives , Anti-Arrhythmia Agents/adverse effects , Digoxin/adverse effects , ATP Binding Cassette Transporter, Subfamily B, Member 1/drug effects , Aged, 80 and over , Amiodarone/adverse effects , Amiodarone/pharmacology , Amiodarone/therapeutic use , Anti-Arrhythmia Agents/pharmacokinetics , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Digoxin/pharmacokinetics , Digoxin/therapeutic use , Dose-Response Relationship, Drug , Dronedarone , Drug Interactions , Drug Monitoring/methods , Female , HumansABSTRACT
A subset of patients with differentiated thyroid carcinoma develop radioiodine refractory (RAIR) incurable disease, which typically has a poor prognosis. The multitargeted tyrosine kinase inhibitor lenvatinib has demonstrated significant improvements in progression-free survival in RAIR thyroid cancers compared to placebos. However, in the phase III SELECT trial of the drug in thyroid cancer, 5.4% of patients on lenvatinib experienced arterial thromboembolic events, with 2.7% experiencing severe grade ≥3 toxicities associated with arterial vascular events. This case study reports a patient with metastatic poorly differentiated follicular thyroid cancer who developed significant obstructive coronary artery disease following initiation of lenvatinib treatment, despite no predisposing cardiovascular risk factors apart from a remote smoking history. The possibility of developing coronary or peripheral artery disease should be considered in patients who are on targeted therapies, such as lenvatinib, even in the absence of traditional cardiovascular risk factors. In addition, baseline cardiac risk assessment and early treatment should be pursued to minimize interruptions to potentially lifesaving cancer therapy.
ABSTRACT
Background: Carfilzomib and other proteasome inhibitors (PIs) have revolutionized treatment of multiple myeloma (MM). PIs have proven to be highly effective, but are associated with significant cardiovascular adverse events (AEs). No prior study has compared the cardiotoxicity of carfilzomib against other PI's and all other classes of medications. Objectives: The purpose of this study is to characterize the cardiotoxicity of carfilzomib with respect to other PIs and all classes of medications using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database and to define the observed cardiotoxicity profile. Methods: The FAERS database was queried between years 2017 and 2020 to identify AEs associated with PIs. Data extracted included concomitant medications used, type and severity of AEs and patient characteristics including age, sex, and time from medication initiation to adverse event. Cardiotoxicities assessed included acute myocardial infarction, heart failure, and supraventricular tachycardia. The reporting odds ratio (ROR) and information component assessed the strength of association between PIs and cardiotoxicity. Results: Over the study period, 21,026 adverse events were reported in patients taking carfilzomib among 55,195 total adverse events in patients taking PI's were identified from 6,548,048 total events reported in the FAERS database. The most common AE associated with carfilzomib was development of heart failure (1116 adverse events); disproportionality analysis revealed a stronger association with hypertension and QT prolongation with carfilzomib than other PI's. Conclusions: While they have demonstrated efficacy and revolutionized treatment of MM, carfilzomib and other PI's are associated with cardiotoxicities.
ABSTRACT
Amyloidosis refers to a group of conditions where abnormal protein-or amyloid-deposits in tissues or organs, often leading to organ malfunction. Amyloidosis affects nearly any organ system, but especially the heart, kidneys, liver, peripheral nervous system, and gastrointestinal tract. Neuromuscular deficits comprise some of its ubiquitous manifestations. Amyloidosis can be quite challenging to diagnose given its clinical heterogeneity and multi-system nature. Early diagnosis with accurate genetic and serologic subtyping is key for effective management and prevention of organ decline. In this review, we highlight the value of a multidisciplinary comprehensive amyloidosis clinic. While such a model exists at numerous clinical and research centers across the globe, the lack of more widespread adoption of such a model remains a major hindrance to the timely diagnosis of amyloidosis. Such a multidisciplinary care model allows for the timely and effective diagnosis of amyloidosis, be it acquired amyloid light amyloidosis (AL), hereditary transthyretin amyloidosis (hATTR), or wild type amyloidosis (TTR-wt), especially in the current era of personalized genomic medicine. A multidisciplinary clinic optimizes the delivery of singular or combinatorial drug therapies, depending on amyloid type, fibril deposition location, and disease progression. Such an arrangement also helps advance research in the field. We present our experience at The Ohio State University, as one example out of many, to highlight the centrality of a multi-disciplinary clinic in amyloidosis care.
ABSTRACT
Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure, arrhythmias, and sudden cardiac death. While CA was previously rapidly fatal, recent advances in diagnosis and treatment have significantly improved outcomes. Advances in cardiac imaging and biomarkers have critically improved the accuracy and efficiency with which CA is diagnosed, even allowing for the noninvasive diagnosis of transthyretin CA. Cardiac magnetic resonance imaging, technetium nuclear imaging, echocardiography, and blood-based biomarkers have established important and complementary roles in the management and advancement of care. At the same time, the development of novel targeted amyloid therapies has allowed patients with CA to live longer and potentially achieve better quality of life. Still, despite this significant progress, there remain critical ongoing questions in the field. Accordingly, within this review we will highlight recent advances in cardiac imaging and therapeutics for CA, while focusing on key opportunities for further optimization of care and outcomes among this growing population. Specifically, we will discuss ongoing debates in the diagnosis of CA, including the interpretation of indeterminate cardiac imaging findings, the best technique to screen asymptomatic transthyretin amyloidosis gene mutation carriers for cardiac involvement, and the ideal method for monitoring response to CA treatment. We will additionally focus on recent advances in treatment for transthyretin amyloidosis-CA, including a discussion of available agents as well as highlighting ongoing clinical trials. Together, these data will allow clinicians to emerge with a greater understanding of the present and future of diagnosis, management, and potentially enhanced outcomes in this rapidly advancing field.