Heart Failure Burden by Autopsy, Guideline-Directed Medical Therapy, and ICD Utilization Among Sudden Deaths.

BACKGROUND: Studies of heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) report high sudden cardiac death (SCD) rates but presume cardiac cause. Underlying causes, guideline-directed medical therapy (GDMT), and implantable cardioverter-defibrillator (ICD) use in community sudden deaths with heart failure (HF) are unknown. OBJECTIVES: This study aims to assess the burden of HF, GDMT, and ICD use among autopsied sudden deaths in the POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, a countywide postmortem study of all presumed SCDs. METHODS: Incident WHO-defined (presumed) SCDs for individuals of ages 18 to 90 years were autopsied via prospective surveillance of consecutive out-of-hospital deaths in San Francisco County from February 1, 2011, to March 1, 2014. Sudden arrhythmic deaths (SADs) had no identifiable nonarrhythmic cause (eg, pulmonary embolism), and are thus considered potentially rescuable with ICD. RESULTS: Of 525 presumed SCDs, 100 (19%) had HF. There were 85 patients with known HF (31 HFpEF, 54 HFrEF) and 15 with subclinical HF (postmortem evidence of cardiomyopathy and pulmonary edema without HF diagnosis). SADs comprised 56% (293 of 525) of all presumed SCDs, and 69% (69 of 100) of HF SCDs. The rates were similar in HFrEF (40 of 54 [74%]) and HFpEF (19 of 31 [61%], P = 0.45). Four SAD patients (4%) had ICDs, 3 of which experienced device failure. Twenty-eight SCDs had ejection fraction ≤35%: 22 (79%) with arrhythmic and 6 (21%) with noncardiac causes. Of the 22 SAD patients, 8 (36%) had no identifiable barrier to ICD referral. Complete use of GDMT in HFrEF was 6%. CONCLUSIONS: One in 5 community sudden deaths had HF; two-thirds had autopsy-confirmed arrhythmic causes. ICD prevention criteria captured only 8% (22 of 293) of all SAD cases countywide; GDMT and ICD use remain important targets for HF sudden death prevention.

Homelessness and Incidence and Causes of Sudden Death: Data From the POST SCD Study.

Importance: Over 580 000 people in the US experience homelessness, with one of the largest concentrations residing in San Francisco, California. Unhoused individuals have a life expectancy of approximately 50 years, yet how sudden death contributes to this early mortality is unknown. Objective: To compare incidence and causes of sudden death by autopsy among housed and unhoused individuals in San Francisco County. Design, Setting, and Participants: This cohort study used data from the Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study, a prospective cohort of consecutive out-of-hospital cardiac arrest deaths countywide among individuals aged 18 to 90 years. Cases meeting World Health Organization criteria for presumed SCD underwent autopsy, toxicologic analysis, and medical record review. For rate calculations, all 525 incident SCDs in the initial cohort were used (February 1, 2011, to March 1, 2014). For analysis of causes, 343 SCDs (incident cases approximately every third day) were added from the extended cohort (March 1, 2014, to December 16, 2018). Data analysis was performed from July 1, 2022, to July 1, 2023. Main Outcomes and Measures: The main outcomes were incidence and causes of presumed SCD by housing status. Causes of sudden death were adjudicated as arrhythmic (potentially rescuable with implantable cardioverter-defibrillator), cardiac nonarrhythmic (eg, tamponade), or noncardiac (eg, overdose). Results: A total of 868 presumed SCDs over 8 years were identified: 151 unhoused individuals (17.4%) and 717 housed individuals (82.6%). Unhoused individuals compared with housed individuals were younger (mean [SD] age, 56.7 [0.8] vs 61.0 [0.5] years, respectively) and more often male (132 [87.4%] vs 499 [69.6%]), with statistically significant racial differences. Paramedic response times were similar (mean [SD] time to arrival, unhoused individuals: 5.6 [0.4] minutes; housed individuals: 5.6 [0.2] minutes; P = .99), while proportion of witnessed sudden deaths was lower among unhoused individuals compared with housed individuals (27 [18.0%] vs 184 [25.7%], respectively, P = .04). Unhoused individuals had higher rates of sudden death (incidence rate ratio [IRR], 16.2; 95% CI, 5.1-51.2; P < .001) and arrhythmic death (IRR, 7.2; 95% CI, 1.3-40.1; P = .02). These associations remained statistically significant after adjustment for differences in age and sex. Noncardiac causes (96 [63.6%] vs 270 [37.7%], P < .001), including occult overdose (48 [31.8%] vs 90 [12.6%], P < .001), gastrointestinal causes (8 [5.3%] vs 15 [2.1%], P = .03), and infection (11 [7.3%] vs 20 [2.8%], P = .01), were more common among sudden deaths in unhoused individuals. A lower proportion of sudden deaths in unhoused individuals were due to arrhythmic causes (48 of 151 [31.8%] vs 420 of 717 [58.6%], P < .001), including acute and chronic coronary disease. Conclusions and Relevance: In this cohort study among individuals who experienced sudden death in San Francisco County, homelessness was associated with greater risk of sudden death from both noncardiac causes and arrhythmic causes potentially preventable with a defibrillator.

Cardiac arrhythmia spot light: Detection of ventricular fibrillation-Not all ICDs are created equal.

Intracardiac device electrograms demonstrating differing VF sensing performance between two manufacturer ICD generators.

Factors Predisposing to Survival After Resuscitation for Sudden Cardiac Arrest.

BACKGROUND: In the POST SCD study, the authors autopsied all World Health Organization (WHO)-defined sudden cardiac deaths (SCDs) and found that only 56% had an arrhythmic cause; resuscitated sudden cardiac arrests (SCAs) were excluded because they did not die suddenly. They hypothesized that causes underlying resuscitated SCAs would be similarly heterogeneous. OBJECTIVES: The aim of this study was to determine the causes and outcomes of resuscitated SCAs. METHODS: The authors identified all out-of-hospital cardiac arrests (OHCAs) from February 1, 2011, to January 1, 2015, of patients aged 18 to 90 years in San Francisco County. Resuscitated SCAs were OHCAs surviving to hospitalization and meeting WHO criteria for suddenness. Underlying cause was determined by comprehensive record review. RESULTS: The authors identified 734 OHCAs over 48 months; 239 met SCA criteria, 133 (55.6%) were resuscitated to hospitalization, and 47 (19.7%) survived to discharge. Arrhythmic causes accounted for significantly more resuscitated SCAs overall (92 of 133, 69.1%), particularly among survivors (43 of 47, 91.5%), than WHO-defined SCDs in POST SCD (293 of 525, 55.8%; p < 0.004 for both). Among resuscitated SCAs, arrhythmic cause, ventricular tachycardia/fibrillation initial rhythm, and white race were independent predictors of survival. None of the resuscitated SCAs due to neurologic causes survived. CONCLUSIONS: In this 4-year countywide study of OHCAs, only one-third were sudden, of which one-half were resuscitated to hospitalization and 1 in 5 survived to discharge. Arrhythmic cause predicted survival and nearly one-half of nonsurvivors had nonarrhythmic causes, suggesting that SCA survivors are not equivalent to SCDs. Early identification of nonarrhythmic SCAs, such as neurologic emergencies, may be a target to improve OHCA survival.

Sex and Racial Differences in Autopsy-Defined Causes of Presumed Sudden Cardiac Death.

[Figure: see text].

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

Importance: QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown. Objective: To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. Design, Setting, and Participants: This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. Exposure: QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). Main Outcomes and Measures: Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. Results: A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. Conclusions and Relevance: These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

[Prevalence of lymph node involvement in patients with endometrial cancer, Colombia 2009-2016: Exploratory analysis of associated factors].

OBJECTIVE: To determine the prevalence of lymph node involvement in patients with endometrial cancer and to explore factors associated with lymph node invasion. METHODS: Prevalence study with exploratory analysis. The study included patients with endometrial cancer who underwent total abdominal hysterectomy plus bilateral salpyingooophorectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy in seven oncology centers in Colombia between 2009 and 2016. Patients who had received prior radiotherapy or chemotherapy, with a histological diagnosis of neuroendocrine tumors, carcinosarcomas or synchronous or metachronous lesions were excluded. Non-probabilistic sampling. Sample size n=290. Measured variables: sociodemographic, clinical and histopathological, and pelvic or para-aortic lymph node involvement. The prevalence for the period is presented. The exploratory analysis was conducted using crude odds ratio (OR) and adjusted OR by means of a multivariate model (unconditional logistic regression). RESULTS: Overall, 467 cases were retrieved. Of them, 163 were excluded because of non-availability of all the variables. In total, 304 patients were studied. The prevalence of lymph node involvement was 15.8 % (48/304). In the crude and adjusted analysis, factors associated with lymph node involvement were lymphovascular invasion (adjusted OR: 9.32; 95 % CI 4.27-21.15) and myometrial invasion (adjusted OR: 3.95; 95 % CI 1.29-14.98). CONCLUSIONS: Of the patients undergoing lymphadenectomy, 15 % have lymph node involvement. Less invasive diagnostic options than radical surgery to ascertain lymph node invasion should be assessed.

TITULO: PREVALENCIA DEL COMPROMISO GANGLIONAR EN PACIENTES CON CÁNCER DE ENDOMETRIO, COLOMBIA 2009-2016: ANÁLISIS EXPLORATORIO DE FACTORES ASOCIADOS. OBJETIVO: Determinar la prevalencia del compro miso ganglionar de pacientes con cáncer de endometrio y hacer una exploración de los factores asociados a la invasión ganglionar. METODOS: Estudio de prevalencia con análisis exploratorio. Se incluyeron pacientes con cáncer de endometrio llevadas a histerectomía abdominal total más salpingooforectomía bilateral y linfadenectomía pélvica, con o sin linfadenectomía paraaórtica en siete centros de oncología de Colombia, en el periodo 2009-2016. Se excluyeron pacientes con radioterapia o quimioterapia previa, diagnóstico histológico de tumores neuroendocrinos, carcinosarcomas, tumores sincrónicos o metacrónicos. Muestreo no probabilístico. Tamaño muestral n = 290. Variables medidas: sociodemográficas, clínicas e histopatológicas y compromiso ganglionar pélvico o paraaórtico. Se presenta la prevalencia de periodo; el análisis exploratorio se realizó por medio de odds ratio (OR) crudo y el ajustado mediante un modelo multivariado (regresión logística no condicional). RESULTADOS: Se obtuvieron 467 casos de los cuales se excluyeron 163 por no presentar la totalidad de las variables, se estudiaron 304 pacientes. La prevalencia del compromiso ganglionar fue del 15,8 % (48/304). Los factores asociados al compromiso ganglionar en el análisis crudo y ajustado fueron la invasión linfovascular (OR ajustado = 9,32; IC 95 %: 4,27-21,15) e invasión miometrial (OR ajustado = 3.95; IC 95 %: 1,29-14,98). CONCLUSIONES: El 15 % de las pacientes sometidas a linfadenectomía tienen compromiso ganglionar. Se deben evaluar alternativas diagnósticas menos invasivas que la cirugía radical para establecer la invasión ganglionar.

Depression in Patients with Tinnitus: A Systematic Review.

OBJECTIVE: Tinnitus is a condition that causes distress and impairment across cognitive, functional, and psychiatric spectra. In the psychiatric realm, tinnitus has long been associated with depression. To better characterize the co-occurrence of depression and tinnitus, we performed a systematic review of the prevalence of depression among patients with tinnitus. DATA SOURCES: We comprehensively examined original studies reporting the prevalence of depression in adult populations with tinnitus, as indexed in the PubMed and Web of Science databases and published from January 2006 to August 2016. REVIEW METHODS: All identified articles were reviewed independently by 2 researchers, with a third reviewer for adjudication. Included studies were evaluated for threats to validity across 3 domains-representativeness, response rate, and ascertainment of outcome-on a 4-point modified Newcastle-Ottawa Quality Assessment Scale. RESULTS: Twenty-eight studies were included, representing 15 countries and 9979 patients with tinnitus. Among the included studies, the median prevalence of depression was 33%, with an interquartile range of 19% to 49% and an overall range of 6% to 84%. Studies were high quality overall, with a mean score of 3.3 (SD = 0.76), and 89% utilized a validated tool to ascertain depression. CONCLUSIONS: We conducted one of the largest contemporary comprehensive reviews, which suggests a 33% prevalence of depression among patients with tinnitus. Our review reaffirms that a substantial proportion of patients with tinnitus have depression, and we recommend that all who treat tinnitus should screen and treat their patients for depression, if present.

Refining the World Health Organization Definition: Predicting Autopsy-Defined Sudden Arrhythmic Deaths Among Presumed Sudden Cardiac Deaths in the POST SCD Study.

BACKGROUND: Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs. METHODS: Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts. RESULTS: Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of ß-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases <1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97). CONCLUSIONS: Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to <1 hour since last normal, at the cost of sensitivity.

The diagnostic pathway of oropharyngeal squamous cell carcinoma in a large U.S. healthcare system.

OBJECTIVE: To examine the current diagnostic pathway of oropharyngeal squamous cell carcinoma (OPSCC) and identify factors associated with time to diagnosis. METHODS: Retrospective cohort study of patients with OPSCC in an integrated healthcare system from January 1, 2013, to December 31, 2013. Patient demographics, tobacco and alcohol use, chief complaint, tumor stage, human papilloma virus (HPV) status, physician factors (diagnosis, antibiotic prescription, performance of endoscopic exam, biopsy), and time intervals were examined. Time variations by patient characteristics and physician practice were assessed. RESULTS: We identified 152 patients with OPSCC. Of those, 90% had stage III to IV disease. The cohort was largely male (85%), white (79%), with HPV-positive tumors (84%). Most common chief complaints were neck mass (52%) and sore throat (20%). Among those with neck a mass, 94% had HPV-positive tumors. Prescription of antibiotics was associated with longer time to first otolaryngology evaluation. Median time from symptom onset to first primary care physician (PCP) contact was 3.0 weeks; from PCP to otolaryngologist was 1.1 weeks, and from otolaryngologist to tissue diagnosis was 0.4 weeks. At the first otolaryngology visit, 82% underwent in-office flexible endoscopy and 58% had same-day biopsy, resulting in rapid time to tissue diagnosis. Diagnostic time intervals did not differ by HPV status. CONCLUSION: The overall diagnostic process was efficient, although initial antibiotic treatment resulted in longer time to first otolaryngology visit. Tumor HPV status was associated with presenting findings but not time to diagnosis. The variation in diagnostic delay time and impact on survival outcomes is unknown and merits further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 1867-1873, 2018.

Diagnostic Pathway of Oral Cavity Cancer in an Integrated Health Care System.

CONTEXT: Survival for patients with oral cavity squamous cell carcinoma (OCSCC) has remained relatively stagnant despite advances in treatment. Few studies have examined why advanced-stage disease is diagnosed in 40% of patients with OCSCC nationally. OBJECTIVE: To characterize the diagnostic pathway of OCSCC in an integrated health care system. DESIGN: Retrospective study of patients with OCSCC (2007-2010). MAIN OUTCOME MEASURES: Referral patterns and demographic, clinical, and tumor characteristics associated with time to diagnosis (diagnostic interval). RESULTS: Of 247 patients, 167 (68%) had early-stage (I/II) disease, 86 (35%) were referred by dentists, and 70 (28%) had a history of premalignancy. The median time (interquartile range) from symptom onset to care sought from a primary care physician (patient interval), from primary care physician to otolaryngologist, and from otolaryngologist to diagnosis was 8.6 (4.0-25.8), 1.0 (0.6-3.1), 0.0 (0.0-3.0) weeks, respectively. These intervals did not differ by demographic characteristics, clinical factors, or tumor stage. Prolonged diagnostic intervals were observed among patients with premalignant lesions. CONCLUSION: The patient interval was the largest component of the total diagnostic interval. The subsequent professional workup proceeded relatively efficiently. Prolonged diagnostic interval in patients with premalignant lesions may reflect the natural history of malignant transformation rather than a delay in diagnosis. However, nearly one-fourth of these cases were diagnosed at an advanced stage; closer surveillance may represent an opportunity for diagnosis at an earlier stage. Surveillance for premalignant lesions and facilitating referrals from dentists may expedite the diagnosis and treatment of OCSCC. Further investigation is warranted.

Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C-Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma.

BACKGROUND: Hepatitis C virus (HCV)(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct-acting anti-viral (DAA) agents that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers. METHODS: We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (cost per quality-adjusted life year gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modeled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with hepatocellular carcinoma MELD exception points. RESULTS: Under base case conditions, the deferred DAA treatment strategy was found to be the "dominant" strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the incremental cost-effectiveness ratio associated with HCV DAA treatment before transplant less than US $150 000/quality-adjusted life-year gained. CONCLUSIONS: Deferring HCV treatment until after liver transplant and maintaining access to the expanded pool of HCV(+) donors appears to be the most cost-effective strategy for well-compensated HCV-infected cirrhotics listed for liver transplantation with hepatocellular carcinoma, even in geographic areas of relatively low HCV(+) donor availability.