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1.
Cureus ; 15(11): e48853, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38106700

ABSTRACT

Thiamine (vitamin B1) is an essential nutrient and one of the eight B vitamins. As a water-soluble vitamin, thiamine is not stored; therefore, a balanced diet is required to ensure adequate intake of this essential vitamin. Thiamine deficiency is known to cause both wet and dry beriberi, but rarely in combination. Thiamine deficiency has also been known to cause QTc prolongation, but the mechanism remains unclear. In the most severe cases, this can lead to the lethal arrhythmia of torsades de pointes. This case describes a patient who became malnourished after a closed head injury and initially presented with seizure-like activity and syncopal episodes with nonspecific numbness. He was found to have prolonged QTc, leading to torsades de pointes requiring an implanted cardioverter defibrillator. With extensive workup, including genetic testing, the patient was found to have indetectable thiamine levels. With supplementation, the patient no longer had any recorded ventricular arrhythmias, and neurological function improved with only residual tingling in the hands. This case emphasizes the profound effects of thiamine deficiency and why this should be included in our differential diagnosis for patients presenting with the sequelae of the signs and symptoms discussed.

2.
J Palliat Med ; 26(4): 481-488, 2023 04.
Article in English | MEDLINE | ID: mdl-36350362

ABSTRACT

Background: Cardiac resynchronization therapy (CRT) improves quality of life (QOL) in heart failure (HF) patients with reduced ejection fraction. Clinicians may have difficulty choosing between CRT with a pacemaker (CRT-P) or a defibrillator (CRT-D) for older patients. CRT-P devices are smaller, have more battery longevity, are less prone to erosions or recalls, and do not deliver shocks. These factors may impact patients' QOL, but data on such comparisons are lacking. Objectives: We examined the impact of CRT-P versus CRT-D on the QOL of older (≥75 years) HF patients who qualified for implantable cardioverter defibrillator therapy. Settings/Subjects/Measurements: We enrolled 101 CRT recipients and assessed QOL at baseline and at six-month post-implant using the Short Form Health Survey (SF-36) and the Minnesota living with heart failure (MLHF) questionnaires. Results: The average age of enrolled patients was 81 years, 27% were women, and 40 received a CRT-P device. After adjusting for baseline QOL score, age, sex, HF functional class, and the occurrence of adverse events, we found no significant differences in QOL outcomes between CRT-P and CRT-D recipients based on either the subscales or the composite scores for the SF-36 or MLHF questionnaires at six-months post-implantation. Conclusions: Older CRT-P and CRT-D recipients report comparable QOL scores six months after device implantation. Larger cohort studies with longer follow-up are needed to accurately assess potential QOL differences between CRT-D and CRT-P recipients to guide clinical decision making and ensure the right balance of risk versus benefit in these patients. Appropriate goals-of-care discussions are the corner stone of clinical decision making regarding defibrillator therapy. As such, even as the data stand at present, there is a need for more deliberate referral of older patients with HF to Palliative Care Specialists, or to Cardiologists trained in Palliative Care Medicine. clinicaltrials.gov listing: NCT03031847.


Subject(s)
Defibrillators, Implantable , Heart Failure , Humans , Female , Aged , Aged, 80 and over , Child, Preschool , Male , Cardiac Resynchronization Therapy Devices , Quality of Life , Treatment Outcome , Heart Failure/therapy
5.
J Clin Invest ; 128(3): 1154-1163, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29457789

ABSTRACT

SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure.


Subject(s)
Heart Failure/genetics , MicroRNAs/genetics , NAV1.5 Voltage-Gated Sodium Channel/genetics , Action Potentials , Aged , Alleles , Animals , Binding Sites , Death, Sudden, Cardiac , Female , Gene Expression Profiling , Genotype , Heart Conduction System/physiopathology , Heart Rate , Homozygote , Humans , Linkage Disequilibrium , Male , Mice , Middle Aged , Oligonucleotide Array Sequence Analysis , Patch-Clamp Techniques , Polymorphism, Single Nucleotide , Rats, Sprague-Dawley
7.
Heart Rhythm ; 13(4): 933-42, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26688064

ABSTRACT

BACKGROUND: Left ventricular ejection fraction (LVEF) response to guideline-directed medical therapy (GDMT) and to early cardiac resynchronization therapy (CRT) in new-onset idiopathic nonischemic cardiomyopathy (NICM) and left bundle branch block (LBBB) is not well described. CRT is recommended if LVEF remains ≤35% after at least 3 months of GDMT. OBJECTIVE: The purpose of this study was to describe LVEF response to GDMT at 3 months and to early CRT in new-onset LBBB-associated idiopathic NICM. METHODS: A retrospective cohort study was performed in subjects with new-onset idiopathic NICM, LVEF ≤35%, and LBBB or narrow (<120 ms) QRS complex morphology. LVEF response between groups was evaluated with log-binomial and linear regression. LVEF response within groups was evaluated using the paired Student t test. RESULTS: In 102 subjects (70 with narrow QRS complex and 32 with LBBB), post-GDMT LVEF was >35% in 39 narrow QRS complex subjects (56%) and 2 LBBB subjects (6%) (P < .0001). The absolute difference between post-GDMT LVEF and initial LVEF was greater in the narrow QRS complex group (16.1% ± 14.6% vs. 3.3% ± 10.7%; P < .0001). Narrow QRS complex, referenced to LBBB, was significantly associated with post-GDMT LVEF >35% (relative risk 10.30; 95% confidence interval 2.63-40.27; P = .0008) and absolute difference between post-GDMT LVEF and initial LVEF (ß = 16.296; standard error = 2.977; P < .0001) in final multivariable analyses. CRT super-response, defined as post-CRT LVEF ≥50%, was observed in 8 of LBBB subjects (35%) who received CRT. CONCLUSION: GDMT did not significantly improve LVEF in new-onset LBBB-associated idiopathic NICM at 3 months. Most remained candidates for CRT, and a high percentage were super-responders. Optimal timing for CRT implantation requires further investigation.


Subject(s)
Bundle-Branch Block/therapy , Cardiac Resynchronization Therapy/standards , Cardiomyopathies/complications , Electrocardiography , Guideline Adherence , Heart Ventricles/physiopathology , Stroke Volume/physiology , Aged , Bundle-Branch Block/etiology , Bundle-Branch Block/physiopathology , Cardiomyopathies/physiopathology , Cardiomyopathies/therapy , Echocardiography , Female , Follow-Up Studies , Heart Conduction System/physiopathology , Heart Ventricles/diagnostic imaging , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome
8.
Europace ; 18(9): 1383-90, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26498162

ABSTRACT

AIMS: Heart failure patients are at increased risk of ventricular arrhythmias and all-cause mortality. However, existing clinical and serum markers only modestly predict these adverse events. We sought to use metabolic profiling to identify novel biomarkers in two independent prospective cohorts of patients with implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD). METHODS AND RESULTS: Baseline serum was quantitatively profiled for 42 known biologically relevant amine-based metabolites among 402 patients from the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) Study (derivation group) and 240 patients from the Genetic Risk Assessment of Defibrillator Events (GRADE) Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. Three amines, N-methyl-l-histidine, symmetric dimethylarginine (SDMA), and l-kynurenine, were derived and validated to be associated with all-cause mortality. The hazard ratios of mortality in PROSE-ICD and GRADE were 1.48 (95% confidence interval 1.14-1.92) and 1.67 (1.22-2.27) for N-methyl-l-histidine, 1.49 (1.17-1.91) and 1.77 (1.27-2.45) for SDMA, 1.31 (1.06-1.63) and 1.73 (1.32-2.27) for l-kynurenine, respectively. l-Histidine, SDMA, and l-kynurenine were associated with ventricular arrhythmia-induced ICD shocks in PROSE-ICD, but they did not reach statistical significance in the GRADE cohort. CONCLUSION: Utilizing metabolic profiling in two independent prospective cohorts of patients undergoing ICD implantation for primary prevention of SCD, we identified several novel amine markers that were associated with appropriate shock and mortality. These findings shed insight into the potential biologic pathways leading to adverse events in ICD patients. Further studies are needed to confirm the prognostic value of these findings.


Subject(s)
Amines/blood , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electric Countershock/instrumentation , Heart Failure/therapy , Primary Prevention/methods , Aged , Arginine/analogs & derivatives , Arginine/blood , Biomarkers/blood , Death, Sudden, Cardiac/etiology , Electric Countershock/adverse effects , Electric Countershock/mortality , Female , Heart Failure/blood , Heart Failure/diagnosis , Heart Failure/mortality , Humans , Kynurenine/blood , Male , Metabolomics , Methylhistidines/blood , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , United States
9.
J Am Coll Cardiol ; 66(23): 2607-2613, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26670060

ABSTRACT

BACKGROUND: The wearable cardioverter-defibrillator (WCD) has emerged as a means of protecting patients with newly diagnosed nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM) against sudden cardiac death while awaiting re-evaluation of cardiac function. OBJECTIVES: This study sought to characterize the risk of appropriate WCD therapy in newly diagnosed NICM and ICM patients according to cardiomyopathy etiology in an independent study. METHODS: Medical records of all patients prescribed a WCD between June 2004 and May 2015 at our institution (n = 639) were analyzed, focusing on 254 patients with newly diagnosed NICM and 271 patients with newly diagnosed ICM. Patients with a prior implantable cardioverter-defibrillator or sustained ventricular arrhythmias were excluded (n = 114). The primary endpoint was appropriate WCD therapy. RESULTS: Median WCD wear time was 61 days (interquartile range [IQR]: 25 to 102 days) per patient and 22 h/day (IQR: 17 to 23 h/day). During 56.7 patient-years, 0 NICM patients received an appropriate WCD shock, whereas 3 (1.2%) received an inappropriate shock. During 46.7 patient-years, 6 (2.2%) ICM patients received an appropriate shock; 5 survived the episode, and 4 survived to hospital discharge. All 6 patients with an appropriate shock were male with QRS duration >120 ms. Two (0.7%) ICM patients received an inappropriate shock. CONCLUSIONS: In this independent, retrospective study, the risk of appropriate WCD therapies in patients with newly diagnosed NICM was minimal. Routine use of the WCD in this population should be prospectively evaluated. The risk of appropriate therapies in newly diagnosed ICM was comparable to that observed in prior observational studies.


Subject(s)
Cardiomyopathies , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electric Countershock , Ventricular Fibrillation , Adult , Aged , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/mortality , Cardiomyopathies/physiopathology , Cardiomyopathies/therapy , Electric Countershock/instrumentation , Electric Countershock/methods , Female , Humans , Male , Middle Aged , Patient Outcome Assessment , Retrospective Studies , Survival Rate , United States/epidemiology , Ventricular Fibrillation/etiology , Ventricular Fibrillation/therapy
10.
J Am Heart Assoc ; 4(8): e001566, 2015 Jul 31.
Article in English | MEDLINE | ID: mdl-26231842

ABSTRACT

BACKGROUND: Reduced left ventricular (LV) ejection fraction increases the risk of ventricular arrhythmias; however, LV ejection fraction has a low sensitivity to predict ventricular arrhythmias. LV dilatation and mass may be useful to further risk-stratify for ventricular arrhythmias. METHODS AND RESULTS: Patients from the Genetic Risk of Assessment of Defibrillator Events (GRADE) study (N=930), a study of heart failure subjects with defibrillators, were assessed for appropriate implantable cardioverter-defibrillator shock and death, heart transplant, or ventricular assist device placement by LV diameter and mass. LV mass was divided into normal, mild, moderate, and severe classifications. Severe LV end-diastolic diameter had worse shock-free survival than normal and mild LV end-diastolic diameter (P=0.0002 and 0.0063, respectively; 2-year shock free, severe 74%, moderate 80%, mild 91%, normal 88%; 4-year shock free, severe 62%, moderate 69%, mild 72%, normal 81%) and freedom from death, transplant, or ventricular assist device compared with normal and moderate LV end-diastolic diameter (P<0.0001 and 0.0441, respectively; 2-year survival: severe 78%, moderate 85%, mild 82%, normal 89%; 4-year survival: severe 55%, moderate 64%, mild 63%, normal 74%). Severe LV mass had worse shock-free survival than normal and mild LV mass (P=0.0370 and 0.0280, respectively; 2-year shock free: severe 80%, moderate 81%, mild 91%, normal 87%; 4-year shock free: severe 68%, moderate 73%, mild 76%, normal 76%) but no association with death, transplant, or ventricular assist device (P=0.1319). In a multivariable Cox proportional hazards analysis adjusted for LV ejection fraction, LV end-diastolic diameter was associated with appropriate implantable cardioverter-defibrillator shocks (hazard ratio 1.22, P=0.020). LV end-diastolic diameter was associated with time to death, transplant, or ventricular assist device (hazard ratio 1.29, P=0.0009). CONCLUSIONS: LV dilatation may complement ejection fraction to predict ventricular arrhythmias. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02045043.


Subject(s)
Arrhythmias, Cardiac/etiology , Hypertrophy, Left Ventricular/complications , Ventricular Dysfunction, Left/complications , Ventricular Function, Left , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , Chi-Square Distribution , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Dilatation, Pathologic , Disease-Free Survival , Electric Countershock/instrumentation , Female , Heart Failure/etiology , Heart Failure/physiopathology , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Humans , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/mortality , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/therapy , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Prospective Studies , Risk Assessment , Risk Factors , Systole , Time Factors , Treatment Outcome , United States , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/mortality , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy
11.
Am J Cardiol ; 115(7): 924-31, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-25682436

ABSTRACT

Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure, Systolic/therapy , Risk Assessment/methods , Aged , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/prevention & control , Female , Follow-Up Studies , Heart Failure, Systolic/mortality , Heart Failure, Systolic/physiopathology , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Severity of Illness Index , Survival Rate/trends , Time Factors , United States/epidemiology
12.
BMJ Case Rep ; 20142014 Mar 05.
Article in English | MEDLINE | ID: mdl-24599427

ABSTRACT

We present an unusual case of disseminated intravascular coagulopathy (DIC) complicating percutaneous laser-assisted lead extraction. DIC has not been previously reported in association with lead extraction. It is possible to have occurred following the denudement of venous endothelium and exposure of underlying fibrous tissue. Practitioners need to be aware of this rare but potentially fatal complication of transvenous lead extraction.


Subject(s)
Device Removal/adverse effects , Disseminated Intravascular Coagulation/etiology , Prosthesis Implantation/adverse effects , Acute Disease , Aged , Blood Transfusion , Defibrillators, Implantable , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/therapy , Equipment Failure , Humans , Male
13.
Ann Thorac Surg ; 91(5): 1348-54, 2011 May.
Article in English | MEDLINE | ID: mdl-21524442

ABSTRACT

BACKGROUND: Renal dysfunction is common before mechanical circulatory support (MCS). Mechanical circulatory support frequently improves renal function, but the impact of pre-MCS renal dysfunction on renal function after cardiac transplantation (CTX) is unknown. METHODS: Patients with MCS from January 1995 until April 2008 at a single center were included if their MCS duration was at least 60 days and they underwent successful CTX. Patients were followed for 1 year after CTX. RESULTS: A total of 116 patients were included in the study. Mechanical circulatory support was biventricular assist device in 28% and left ventricular assist device in 72% (continuous flow left ventricular assist device, 14%). Mean duration of MCS was 124 days. Patients were grouped according to tertiles of pre-MCS creatinine clearance (CrCl): group 1, CrCl less than 45 mL/min; group 2, CrCl between 45 and 65 mL/min inclusive; and group 3, CrCl more than 65 mL/min. Group 3 had the best renal outcomes both after MCS and 1 year after CTX. Regardless of group, patients who had a CrCl of at least 60 mL/min before CTX had similar 1-year posttransplant CrCl (55 versus 53 versus 56 mL/min for groups 1 through 3, respectively; not significantly different). However, the ability to achieve this level of renal function after MCS was less likely in those with the worst renal function before the initiation of MCS (53% versus 74% versus 90% for groups 1 through 3, respectively; p=0.001). CONCLUSIONS: The use of MCS leads to improvements in renal function in patients after MCS. However, the renal outcomes after CTX seem to be more dependent on the level of renal function achieved during MCS than on the level of renal function before MCS.


Subject(s)
Heart Failure/diagnosis , Heart Failure/surgery , Heart-Assist Devices , Renal Insufficiency/diagnosis , Analysis of Variance , Cohort Studies , Creatinine/urine , Female , Follow-Up Studies , Heart Failure/complications , Heart Transplantation/methods , Humans , Kidney Function Tests , Male , Middle Aged , Monitoring, Physiologic/methods , Multivariate Analysis , Postoperative Care/methods , Preoperative Care/methods , Reference Values , Renal Insufficiency/complications , Retrospective Studies , Risk Assessment , Time Factors , Treatment Outcome , Waiting Lists
14.
J Cardiovasc Electrophysiol ; 19(12): 1316-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18631265

ABSTRACT

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is thought to be a disease of the young, with the majority of newly diagnosed patients under 40 years of age. Establishing this diagnosis in elderly patients may be challenging, and a few reports exist of patients older than 70 years diagnosed with ARVD/C at autopsy. We report the case of an octogenarian with antemortem newly diagnosed ARVD/C. This case report represents the oldest patient to date to have a newly established diagnosis of ARVD/C and highlights the difficulty in making the diagnosis in the elderly.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Electrocardiography/methods , Aged, 80 and over , Humans , Male
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