Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

BACKGROUND: Since the initial clinical description of hypertrophic cardiomyopathy (HCM) over 60 years ago, sudden cardiac death (SCD) has been the most visible and feared complication of HCM. OBJECTIVES: This study sought to characterize the temporal, geographic, and age-related trends of reported SCD rates in adult HCM patients. METHODS: Electronic databases were systematically searched up to November 2021 for studies reporting on SCD event rates in HCM patients. Patients with SCD equivalents (appropriate implantable cardioverter-defibrillator [ICD] shocks and nonfatal cardiac arrests) were not included. A random-effects model was used to pool study estimates calculating the overall incidence rates (IR) for each time-era, geographic region, and age group. We analyzed 2 periods (before vs after 2000, following clinical implementation of ICD in HCM). Following 2000, 5-year intervals were used to demonstrate the temporal change in SCD rates. RESULTS: A total of 98 studies (N = 70,510 patients and 431,407 patient-years) met our inclusion criteria. The overall rate of HCM SCD was 0.43%/y (95% CI: 0.37-0.50%/y; I2 = 75%; SCD events: 1,938; person-years of follow-up: 408,715), with young patients (<18 years of age) demonstrating a >2-fold-risk for sudden death vs adult patients 18-60 years of age (IR: 1.09%; 95% CI: 0.69%-1.73% vs IR: 0.43%; 95% CI: 0.37%-0.50%) (P value for subgroup differences <0.01). Contemporary SCD rates from 2015 to present were 0.32%/y and significantly lower compared with 2000 or earlier (IR: 0.32%; 95% CI: 0.20%-0.52% vs IR: 0.73%; 95% CI: 0.53%-1.02%, respectively). Reported SCD rates for HCM were lowest in North America (IR: 0.28%; 95% CI: 0.18%-0.43%,) and highest in Asia (IR: 0.67%; 95% CI: 0.54%-0.84%). CONCLUSIONS: Contemporary HCM-related SCD rates are low (0.32%/y) representing a 2-fold decrease compared with prior treatment eras. Young HCM patients are at the highest risk. The maturation of SCD risk stratification strategies and the application of primary prevention ICD to HCM are likely responsible for the notable decline over time in SCD events. In addition, worldwide geographic disparities in SCD rates were evident, underscoring the need to increase access to SCD prevention treatment for all HCM patients.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States.

BACKGROUND AND AIMS: Evidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. METHODS: Data were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988-1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11-5.00) or FE2 (HR: 1.89, 95%CI: 1.01-3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. CONCLUSIONS: In this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

Are Serbian and English listeners insensitive to lexical pitch accents in Serbian?

The paper investigated possible perceptual insensitivity effects in the perception of lexical pitch accents by native and non-native listeners, that is, by Serbian and English listeners, respectively. The objective of the study was to explore which word-prosodic categories listeners used when they were required to contrast and recall sequences of lexical pitch accents. To that effect, Serbian and English listeners performed a Sequence Recall Task (SRT) in which they contrasted pairs of non-words with different Serbian lexical pitch accent types, and recalled the sequences of these non-words under different memory load conditions. Listeners' answers were coded correct and incorrect and the accuracy scores between the groups were compared and analyzed. Both groups had almost identical levels of accuracy and they performed well above chance level on each contrast. Neither group exhibited any effects of perceptual insensitivity to lexical pitch accents. English (non-native) listeners did not differ in their performance from native Serbian listeners, which, contrary to what previous research suggested, implied that one's native language word-prosodic category inventory did not preclude the encoding of non-native word-prosodic categories. Instead, non-native listeners were capable of deploying different prosodic resources such as post-lexical pitch accents to recall the sequences.

Hypogonadism in Males With Genetic Neurodevelopmental Syndromes.

Genetic syndromes that affect the nervous system may also disrupt testicular function, and the mechanisms for these effects may be interrelated. Most often neurological signs and symptoms predominate and hypogonadism remains undetected and untreated, while in other cases, a thorough evaluation of a hypogonadal male reveals previously unrecognized ataxia, movement disorder, muscle weakness, tremor, or seizures, leading to a syndromic diagnosis. Androgen deficiency in patients with neurological diseases may aggravate muscle weakness and fatigue and predispose patients to osteoporosis and obesity. The purpose of this mini review is to provide a current understanding of the clinical, biochemical, histologic, and genetic features of syndromes in which male hypogonadism and neurological dysfunction may coexist and may be encountered by the clinical endocrinologist.

Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAID Trial.

BACKGROUND: The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. OBJECTIVES: This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. METHODS: Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. RESULTS: Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age ≥65 years, New York Heart Association functional class ≥III, QRS complex (≥130 ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95% CI: 0.55-0.84; P < 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95% CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95% CI: 0.47-0.86; P < 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95% CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. CONCLUSIONS: In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Impact of Smoking, Obesity and Maternal Diabetes on SHBG Levels in Newborns.

BACKGROUND: Low levels of SHBG have become a marker for insulin resistance and diabetes. Babies born to mothers who are obese, have diabetes, or smoke during pregnancy are at greater risk of developing obesity and diabetes later in life. AIMS: To examine the impact of maternal obesity, diabetes and smoking on SHBG levels in newborns. STUDY DESIGN: This cross-sectional study is part of an ongoing multicenter, longitudinal study. SUBJECTS: 98 healthy newborns and their parents, including 16 mothers with diabetes and 31 mothers with a smoking history. OUTCOME MEASURES: Cord blood and second day venipuncture samples were collected for measurement of SHBG and insulin. RESULTS: Babies born to mothers with diabetes had lower SHBG levels in cord blood [14.0 (8.9-20.4) vs. 19.6 (14.9-25.1) nmol/L; p=0.011] and on day 2 [18.8 (12.6-21.2) vs. 22.9 (17.1-29.1) nmol/L; p=0.015] than controls. Maternal diabetes remained negatively associated with SHBG levels in cord blood (p=0.02) and on day 2 (p=0.04) when adjusted for mothers' age, smoking status, pre-pregnancy weight and weight gain during pregnancy. SHBG levels in cord blood and day 2 samples were similar in babies born to mothers who were overweight-obese but not diabetic vs. normal weight, or were smokers when compared to non-smokers. CONCLUSIONS: SHBG levels are lower in newborns born to mothers with diabetes than without diabetes, and may be a marker for babies' life-long risk for abnormal metabolic health. On the other hand, the adverse effects of tobacco smoke on the fetus do not appear to directly influence SHBG levels.

Importance of newer cardiac magnetic resonance-based risk markers for sudden death prevention in hypertrophic cardiomyopathy: An international multicenter study.

BACKGROUND: The sudden death (SD) risk stratification algorithm in hypertrophic cardiomyopathy (HCM) has evolved, underscored recently by novel cardiac magnetic resonance (CMR)-based risk markers (left ventricular apical aneurysm, extensive late gadolinium enhancement, and end-stage disease with systolic dysfunction) incorporated into the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) HCM guidelines. OBJECTIVE: The purpose of this study was to assess the specific impact of newer, predominantly CMR-based risk markers in a large multicenter HCM population that underwent primary prevention implantable cardioverter-defibrillator (ICD) implants. METHODS: Longitudinal study of 1149 consecutive HCM patients from 6 North American and European HCM centers prospectively judged to be at high SD risk based on ≥1 AHA/ACC individual risk markers and prophylactically implanted with an ICD was performed. European Society of Cardiology (ESC) risk score was retrospectively analyzed with respect to the known clinical outcome. RESULTS: Of 1149 patients with an ICD, 162 (14%) experienced device therapy terminating ventricular tachycardia/ventricular fibrillation 4.6 ± 4.2 years after implant. CMR-based markers solely or in combination led to ICD implantation in 49 of the 162 patients (30%) experiencing device therapy. Particularly low ESC scores (<4%/5 years) would have excluded an ESC ICD recommendation for 67 patients who nevertheless experienced appropriate ICD therapy, including 26 with the CMR-based risk markers not part of the ESC formula. CONCLUSION: Identification and incorporation of novel guideline-supported CMR-based risk markers enhance selection of HCM patients for SD prevention with ICDs. Absence of CMR-based markers from the ESC risk score accounts, in part, for it not identifying many HCM patients with SD events. These data support inclusion of CMR as a routine part of HCM patient evaluation and risk stratification.

Endocrine Dysfunction in Patients With Myotonic Dystrophy.

Myotonic dystrophy is a dominantly inherited multisystem disorder that results from increased CTG repeats in the 3' region of the myotonic dystrophy protein kinase gene (DMPK). The mutant DMPK mRNA remains in the nucleus and sequesters RNA-binding proteins, including regulators of mRNA splicing. Myotonic dystrophy is characterized by a highly variable phenotype that includes muscle weakness and myotonia, and the disorder may affect the function of many endocrine glands. DMPK mRNA is expressed in muscle, testis, liver, pituitary, thyroid, and bone; the mutated form leads to disruption of meiosis and an increase in fetal insulin receptor-A relative to adult insulin receptor-B, resulting in adult primary testicular failure and insulin resistance predisposing to diabetes, respectively. Patients with myotonic dystrophy are also at increased risk for hyperlipidemia, nonalcoholic fatty liver disease, erectile dysfunction, benign and malignant thyroid nodules, bone fractures, miscarriage, preterm delivery, and failed labor during delivery. Circulating parathyroid hormone and adrenocorticotropic hormone levels may be elevated, but the mechanisms for these associations are unclear. This review summarizes what is known about endocrine dysfunction in individuals with myotonic dystrophy.

SHBG and total testosterone levels in men with adult onset hypogonadism: what are we overlooking?

BACKGROUND: Adult onset male hypogonadism (AOH) is a common clinical condition whose diagnosis and management are controversial, and is often characterized by a low level of SHBG, but our understanding of why testosterone levels are low when SHBG is low is incomplete. METHODS: This retrospective chart review was performed to compare the relationship between SHBG and testosterone in the plasma of men presenting for evaluation of AOH with a cohort of men treated chronically with transdermal testosterone. RESULTS: The level of SHBG was < 30 nmol/L in 73% of men who presented for evaluation of AOH, and was inversely proportional to BMI in both the untreated and the testosterone-treated men. As in previous populations, the level of SHBG was highly positively correlated (r = 0.71, p < 0.01) with the total testosterone level in untreated men presenting for evaluation of AOH, but no relationship was found between the level of SHBG and total testosterone among men who were being treated with a transdermal testosterone preparation. CONCLUSIONS: These findings further support the idea that SHBG regulates testicular negative feedback either directly or by modulating the entry of testosterone or estradiol into cells in the hypothalamus and/or pituitary to control gonadotropin synthesis and secretion which explains in part the low testosterone levels in men with AOH. TRIAL REGISTRATION: Not applicable.

The hepatic lipidome and HNF4α and SHBG expression in human liver.

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

PACAP: A regulator of mammalian reproductive function.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an ancestral molecule that was isolated from sheep hypothalamic extracts based on its action to stimulate cAMP production by pituitary cell cultures. PACAP is one of a number of ligands that coordinate with GnRH to control reproduction. While initially viewed as a hypothalamic releasing factor, PACAP and its receptors are widely distributed, and there is growing evidence that PACAP functions as a paracrine/autocrine regulator in the CNS, pituitary, gonads and placenta, among other tissues. This review will summarize current knowledge concerning the expression and function of PACAP in the hypothalamic-pituitary-gonadal axis with special emphasis on its role in pituitary function in the fetus and newborn.

Signaling pathways and promoter regions that mediate pituitary adenylate cyclase activating polypeptide (PACAP) self-regulation in gonadotrophs.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is thought to play a role in the development and regulation of gonadotrophs. PACAP levels are very high in the rodent fetal pituitary, and decline substantially and rapidly at birth, followed by a significant rise in FSHß and GnRH-R expression. Because there is evidence that PACAP stimulates its own transcription, we propose that this self-regulation is interrupted around the time of birth. To begin to examine the mechanisms for PACAP self-regulation, we used two well-established gonadotroph cell lines, αT3-1 cells and the more mature LßT2 cells which were transfected with a PACAP promoter-reporter construct As in vivo, the basal PACAP transcription level is significantly lower in the more mature LßT2 cells in which basal cAMP signaling is also much reduced. The PACAP promoter was stimulated by PACAP in both cell lines. Treatment with inhibitors of second messenger pathways implicated PKA, PKC and MAPK in PACAP transcription. Three regions of the PACAP promoter were found to confer inhibition or stimulation of PACAP transcription. By inhibiting cAMP response element binding (CREB) activity and mutating a proximal CREB binding site, we found that CREB is essential for promoter activation. Finally, overexpression of PACAP receptor HOP1 isoform, to increase the level in LßT2 cells to that of αT3-1 cells and simulate the E19 pituitary, increased PACAP- stimulated sensitivity and significantly altered downstream gene transcription. These results provide novel insight into the feed-forward regulation of PACAP expression that may help initiate gonadotroph function at birth.

Family history of premature myocardial infarction modifies the associations between bilateral oophorectomy and cardiovascular disease mortality in a US national cohort of postmenopausal women.

OBJECTIVE: To test the hypothesis that a family history of premature myocardial infarction (FHPMI) will modify the associations between bilateral salpingo-oophorectomy (BSO) and mortality due to heart disease (HD), cardiovascular disease (CVD), or all-cause mortality with stronger associations observed for BSO occurring before 45 years. METHODS: We analyzed data from 2,763 postmenopausal women aged 40 years or older who participated in the National Health and Nutrition Examination Survey (1988-1994) and were followed through December 31, 2015. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes (HD, CVD, and all-cause). RESULTS: At baseline, the average age was 62 years. There were 610 women with BSO, 338 women with FHPMI, and 95 women with both BSO and FHPMI. During a median follow-up of 22 years, 1,713 deaths occurred of which 395 and 542 were attributed to HD and CVD, respectively. In models adjusting for CVD risk factors and hormone therapy use, HD mortality was greater among women with both BSO and FHPMI compared to those without either of these conditions (HR: 2.88, 95% CI: 1.72-4.82, PInteraction = 0.016). HD mortality was higher among women with FHPMI and BSO at an earlier age (<45 y: HR: 4.32, 95% CI: 1.95-9.50 vs ≥45 y: HR: 1.60, 95% CI: 0.63-4.09). Similar observations were seen for CVD and all-cause mortality. CONCLUSIONS: In this study, the risk of HD, CVD, and all-cause mortality in women with BSO was modified by an FHPMI with the risk limited to women undergoing BSO at younger ages.

Weight-Bearing Physical Activity Influences the Effect of Vitamin D on Bone Turnover Markers in Patients with Intellectual Disability.

OBJECTIVES: Individuals with intellectual disabilities (IDs) are at increased risk for low bone mass and fragility fractures, and those who are nonambulatory may be at even higher risk. Patients with IDs often are vitamin D deficient, but there is little information concerning how vitamin D treatment of patients with IDs affects markers of bone formation and resorption. METHODS: We performed a retrospective analysis of 23 institutionalized individuals with IDs who were the subject of a performance improvement continuing medical education project designed to reduce risk for fracture by optimizing serum vitamin D levels. Patients were divided into those with normal weight-bearing (NWB) physical activity (15 patients: 14 men, 1 woman) and those with low weight-bearing (LWB) physical activity (8 patients: 7 men, 1 woman). All of the subjects received 50,000 IU of vitamin D3 weekly for 4 to 8 weeks, followed by a maintenance dose of 50,000 IU monthly for 3 to 6 months. Bone turnover markers (type 1 cross-linked C-telopeptide [CTX], type 1 N-terminal propeptide [P1NP], and parathyroid hormone [PTH]) and 25(OH)-vitamin D levels were measured before and after vitamin D supplementation. RESULTS: At baseline, there were no significant differences in the serum levels of 25OH-D, PTH, P1NP, or CTX between the two groups (NWB and LWB). Vitamin D levels were increased to a higher value in LWB subjects than in NWB subjects (61 ± 4.1 vs 48.4 ± 2.2 ng/mL, P < 0.001). Vitamin D treatment suppressed PTH (20.5% ± 14.3% vs 31.4% ± 7.7%, P = not significant) and P1NP (33.0% ± 6.2% vs 29.4% ± 6.9%, P = not significant) similarly in both groups. Although CTX levels declined by 26.4% ± 5.3% (P = 0.0002) in NWB individuals (as anticipated), vitamin D supplementation resulted in an unexpected 25.8% ± 8% increase (P = 0.01) in CTX in LWB individuals, suggesting osteoclast activation. CONCLUSIONS: Although high-dose vitamin D appeared to suppress osteoclast activity in NWB adults with IDs, the increase in serum CTX levels in those with LWB activity implies activation of osteoclasts that could exacerbate their unique low bone mass and increase fracture risk. The results support the use of a lower-dose vitamin D regimen in this patient group with LWB.

Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). OBJECTIVES: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. METHODS: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. RESULTS: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. CONCLUSIONS: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators.

BACKGROUND: High-risk patients with hypertrophic cardiomyopathy (HCM) are identified by contemporary risk stratification and effectively treated with implantable cardioverter-defibrillators (ICDs). However, long-term HCM clinical course after ICD therapy for ventricular tachyarrhythmias is incompletely understood. METHODS AND RESULTS: Cohort of 486 high-risk HCM patients with ICDs was assembled from 8 international centers. Clinical course and device interventions were addressed, and survey questionnaires assessed patient anxiety level and psychological well-being related to ICD therapy. Of 486 patients, 94 (19%) experienced appropriate ICD interventions terminating ventricular tachycardia/ventricular fibrillation, 3.7% per year for primary prevention, over 6.4±4.7 years. Of 94 patients, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions; 74 of these 87 (85%) remained in classes I/II without significant change in clinical status over the subsequent 5.9±4.9 years (up to 22). Among the 94 patients, there was one sudden death (caused by device failure; 1.1%); 3 patients died from other HCM-related processes unrelated to arrhythmic risk (eg, end-stage heart failure). Post-ICD intervention, freedom from HCM mortality was 100%, 97%, and 92% at 1, 5, and 10 years, distinctly lower than in ischemic or nonischemic cardiomyopathy ICD trials. HCM patients with ICD interventions reported heightened anxiety in expectation of future shocks, but with intact general psychological well-being and quality of life. CONCLUSIONS: In HCM, unlike ischemic heart disease, prevention of sudden death with ICD therapy is unassociated with significant increase in cardiovascular morbidity or mortality, or transformation to heart failure deterioration. ICD therapy does not substantially impair overall psychological and physical well-being.

Clinical Significance of J Waves in Patients Undergoing Therapeutic Hypothermia for Out-of-Hospital Cardiac Arrest.

BACKGROUND: Hypothermia is associated with the development of J waves. However, little is known about the impact of these electrocardiogram (ECG) findings on the development of ventricular arrhythmias and patient outcomes during therapeutic hypothermia (TH) postresuscitation from out-of-hospital cardiac arrest (OHCA). We investigated the prevalence of J waves in OHCA patients prior to and during TH. Additionally, we explored the incidence of atrial and ventricular arrhythmias and in-hospital mortality for patients with and without J waves either at baseline, during TH, or both. METHODS: We conducted a retrospective analysis of patients who suffered OHCA and underwent TH (goal temperature of 32-34°C). Fifty-nine patients were stratified dependent upon the presence of or the development of J waves on surface ECGs. Descriptive analysis and logistic regression modeling were used to assess the population differences and mortality, respectively, between patients who developed J waves during TH and those who did not. RESULTS: There was no difference in the development of in-hospital atrial or ventricular arrhythmias between patients with J waves present during TH (16%) and those without (17.6%, P = 0.834). Compared to patients without J waves at baseline and during TH, those with J waves present both at baseline and during TH had significantly worse survival (hazard ratio = 12.42, P = 0.046). CONCLUSIONS: While J waves are common ECG findings during TH in patients resuscitated from OHCA, our study demonstrated an increase in mortality for patients with J waves present both at baseline and during TH.