Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection.

BACKGROUND: We aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. METHODS: Consecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between 2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P), variants of uncertain significance, and gene-negative (Gen-N) groups. RESULTS: A total of 407 patients were included: mean age 53.7±15.4 years, 64.4% women, and 38% with reported family history of TAAD. Thirty-seven (9.1%) were Gen-P; 147 (36.1%) had a variant of uncertain significance. Maximal aneurysm diameter was 4.78 mm larger in Gen-P than the other groups (P=.0003). In 162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs 0.89 mm/year, respectively; P<.001). Aneurysms were 20% more likely to require surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. CONCLUSION: While aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria.

Hypertrophic Cardiomyopathy-Septal Perforator Arteries Doppler Flow Dynamics.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have been shown to exhibit abnormal diastolic vessel flow; however, flow pattern profiles and their possible association with different grades of diastolic dysfunction have not been studied. Color Doppler two-dimensional echocardiography permits visualization of the septal perforator arteries, and pulsed-wave Doppler allows recording of diastolic septal artery flow (SAF). Through routine visualization of the septal perforator arteries and acquisition of SAF, we noticed 3 patterns of SAF in patients with HCM. In this study, we aimed to assess the feasibility of the acquisition of SAF and to describe types of SAF in an HCM cohort and their associations with diastolic function. METHODS: We reviewed two-dimensional echocardiograms and the electronic records of 108 patients with HCM in whom septal artery color and spectral Doppler had been performed. The peak diastolic and end-diastolic velocities, diastolic slope, diastolic flow time-velocity integral, and systolic flow reversal of the septal perforator arteries were recorded with pulsed-wave Doppler. Echocardiographic and clinical characteristics were analyzed. RESULTS: A reproducible pulsed-wave Doppler tracing was recorded in 54% of patients with HCM. Three distinct patterns of SAF were identified: type 1-smooth, linear holodiastolic velocity decrease; type 2-with presence of an atrial dip; and type 3-biphasic velocity decrease with an early, rapid diastolic slope and a mid-to-late gentle slope. These 3 SAFs correlated with different grades of diastolic dysfunction. CONCLUSION: Septal artery flow could be detected in more than 50% of patients with HCM. Three distinct types of SAF were identified, correlating with different grades of diastolic dysfunction. These 3 types of SAF can provide additional information about left ventricular end-diastolic pressure and diastolic function in patients with HCM in whom diastolic function may be difficult to determine.

Myocardial work indices in bileaflet mitral valve prolapse patients.

AIMS: Mechanisms underlying left ventricular dysfunction and arrhythmogenesis in bileaflet mitral valve prolapse (BMVP) patients are not well defined. Myocardial work index (MWI) is a noninvasive assessment that correlates with myocardial oxygen consumption. We aimed to compare global and regional MWI in BMVP patients with normal controls. METHODS AND RESULTS: In this retrospective study, we calculated MWI in BMVP patients and controls using GE EchoPAC (GE Healthcare, Chicago, IL) software. Of 147 BMVP patients (59% women, mean age 54 ± 15 years), 16 had a flail mitral leaflet. There was regional heterogeneity in MWIs, with increased posterolateral trident myocardial work (2099 ± 271 vs. 1895 ± 321 mm Hg%, P = .039), constructive work (2831 ± 366 vs. 2257 ± 338 mm Hg%, P < .001), wasted work (87 [52-194] vs. 71 [42-103] mm Hg%, P = .015), peak systolic strain (-23.0 ± 2.4 vs. -19 ± 3%, P < .001), and reduction in myocardial work efficiency (95.00 [93.50-97.75] vs. 96.75 (95.00-97.75) %, P = 0.020) in 100 BMVP patients compared with age- and sex-matched controls. BMVP patients' basal septal wall MWIs were lower than those of controls. The higher work indices in patients with BMVP were reduced in those who developed flail leaflets. No significant differences in work indices were seen between ventricular arrhythmia and non-arrhythmia BMVP patients. CONCLUSION: Regional differences in MWIs were noted in the BMVP patients compared with controls, with overall reduced myocardial efficiency in the posterolateral trident and basal septal regions. In cross-sectional analysis, MWIs were not different in patients with ventricular tachyarrhythmias. Impact of MWI in long-term prognosis needs to be determined.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation.

Age-Based Outcomes in Patients Who Underwent Septal Reduction Therapy.

There are no national data on age-based outcomes of septal reduction therapy. Using the National Inpatient Sample, we included all adult patients who underwent septal myectomy (SM) or alcohol septal ablation (ASA) from 2005 to 2019. The primary objective was to evaluate the in-hospital mortality and new permanent pacemaker (PPM) placement after SM and ASA in 3 age groups. In total, 9,564 patients underwent SM and 5,084 underwent ASA. Compared with the age group 18 to 39 years, the odds of in-hospital mortality after SM were similar in age group 40 to 64 years and 4.46 times higher than in age group ≥65 years; the higher mortality in the older group was explained by higher co-morbidity burden on the risk-adjusted analysis. Furthermore, compared with age group 18 to 39 years, the odds of new PPM placement after SM were higher in the age groups 40 to 64 years and ≥65 years, despite the risk adjustment (adjusted odds ratio [AOR] 3.17, 95% confidence interval [CI] 1.33 to 7.58 and AOR 4.39, 95% CI 1.78 to 10.8, respectively). The odds of in-hospital mortality after ASA were similar in age groups 65 to 79 years and 18 to 64 years. However, the odds of in-hospital mortality were higher in the age group ≥80 years than in the age group 18 to 64 years, although this difference were not present after risk adjustment. The odds of new PPM after ASA were higher for the age groups 65 to 79 years and ≥80 years than age group 18 to 64 years, despite the risk adjustment (AOR 1.78, 95% CI 1.22 to 2.60 and AOR 3.10, 95% CI 2.09 to 6.57, respectively). Finally, we also estimated these absolute risks in different age groups. In conclusion, this national data will inform health care providers to better understand the aged-based risks of outcomes after septal reduction therapy.

Myocardial Work in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Pressure-strain loop analysis is a novel echocardiographic technique to calculate myocardial work indices that has not been applied to patients with apical hypertrophic cardiomyopathy (ApHCM). We hypothesized that myocardial work indices differ between patients with ApHCM and those with non-ApHCM. This study aimed to (1) evaluate myocardial work indices in patients with ApHCM compared with those with non-ApHCM, (2) describe associations with relevant clinical variables, and (3) examine associations with significant late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. METHODS: We retrospectively identified 48 patients with ApHCM and 69 with non-ApHCM who had measurements of global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. We evaluated available cardiac magnetic resonance imaging data on 34 patients with ApHCM and 51 with non-ApHCM. Multivariable regression models correcting for traditional cardiac risk factors were used to evaluate the associations of myocardial work indices with relevant clinical variables. RESULTS: Median GLS (-11% vs -18%, P < .001), GWI (966 mm Hg% vs 1803 mm Hg%, P < .001), and GCW (1,050 mm Hg% vs 1,988 mm Hg%, P < .001) were significantly impaired in patients with ApHCM compared with those with non-ApHCM. Increasing N-terminal pro b-type natriuretic peptide, abnormal ultrasensitive troponin, and increasing maximal left ventricular wall thickness were significantly associated with reduced GWI and GCW in patients with ApHCM (P < .05). Global constructive work had only modest accuracy (area under the curve [AUC] = 0.70) to predict LGE in patients with ApHCM. However, in patients with non-ApHCM, GLS was the strongest predictor of LGE (AUC = 0.91), with a -17% cutoff yielding 81% sensitivity and 80% specificity. CONCLUSION: Myocardial work indices are significantly impaired in patients with ApHCM compared to those with non-ApHCM and correlate with important clinical variables. Global longitudinal strain, GWI, and GCW are more strongly predictive of fibrosis in patients with non-ApHCM than ApHCM.

Seasonal Variation in the Incidence of In-Hospital Cardiac Arrest.

BACKGROUND: Seasonal variation in cardiovascular outcomes, including out-of-hospital cardiac arrest, has been described. OBJECTIVES: This study aimed to investigate seasonal differences in the incidence of in-hospital cardiac arrest (IHCA) and associated mortality. METHODS: Using National Inpatient Sample data from 2005 to 2019, we determined the incidence of IHCA in 4 seasons. The primary objective was to evaluate overall seasonal trends in the incidence of IHCA and trends stratified by sex, age, and region. The secondary aim was to determine common causes of admission that led to IHCA, differences in those with shockable vs nonshockable IHCA, independent predictors of IHCA, and seasonal variation in IHCA-related in-hospital mortality and length of stay. RESULTS: A consistent winter peak was observed in the incidence of IHCA in both male and female patients over the years in all age groups except young (<45 years) and in all regions. In 2019, both unadjusted and risk-adjusted odds of IHCA were higher (OR: 1.13; P < 0.001; adjusted OR: 1.08; P = 0.033) in winter than in summer. Patients with shockable IHCA were mainly admitted for cardiac and those with nonshockable IHCA for noncardiac conditions. No seasonal variation was observed in in-hospital mortality after IHCA. Therefore, seasonal variation exists, with a higher IHCA event rate in winter than summer. CONCLUSIONS: Improving insights into factors that influence the higher IHCA event rate during winter may help with proper resource allocation, development of strategies for early recognition of patients vulnerable to IHCA, and closer monitoring and optimization of care to prevent IHCA and improve outcomes.

Regional Disparities in the Use of Septal Reduction Therapy and Associated Outcomes in the United States (from a Real-World Database).

The regional differences in the use of septal reduction therapies and the associated outcomes in patients with Hypertrophic obstructive cardiomyopathy (HOCM) are unknown. The primary objective of our study was to evaluate the regional disparities in the use of septal reduction therapies, including septal myectomy and alcohol septal ablation, in patients with HOCM. The secondary objective was to analyze the regional differences in the outcomes in these patients. Patients with HOCM had 87% higher risk-adjusted odds of getting septal myectomy (adjusted odds ratio 1.87, p = 0.03) and 37% lower risk-adjusted odds of getting alcohol septal ablation (adjusted odds ratio 0.63, p = 0.03) in the Midwest than in the Northeast. The in-hospital mortality rate was higher for patients who underwent septal myectomy in the South versus the Northeast on the unadjusted analysis. These differences persisted despite the adjustment for demographic and clinical characteristics. Additional adjustment for hospital volume partially explained these disparities, but the adjustment for both hospital volume and hospital teaching status completely explained these disparities. The risk-adjusted in-hospital mortality in patients who underwent alcohol septal ablation was similar in the South versus other regions. In conclusion, regional disparities may exist in the use of septal myectomy and alcohol septal ablation, and patients with HOCM should be referred to high-volume teaching hospitals for septal myectomy for better outcomes, which may also eliminate the extra burden of hospital mortality in the South.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

Hypertrophic cardiomyopathy in identical twins: a case series.

Background: Hypertrophic cardiomyopathy in identical twins is rare. Cases of hypertrophic cardiomyopathy with homogenous and heterogeneous phenotypes have been described in the literature. Case summary: We report a pair of monozygotic twins (Twin A and Twin B) with identical morphological expression of hypertrophic cardiomyopathy. On initial evaluation, both twins had resting left ventricular outflow tract obstruction, Grade II diastolic dysfunction, and New York Heart Association (NYHA) Class II symptoms, but they had a different clinical course afterward. Twin A progressed from NYHA Class II to Class III with a high left ventricular outflow tract pressure gradient that was unresponsive to medical treatment and required alcohol septal ablation. Twin B responded very well to medical treatment. Both patients had no risk factors for sudden cardiac death, and neither required an implantable cardioverter defibrillator. Discussion: The morphology of hypertrophic cardiomyopathy has a strong genetic basis, but epigenetic factors may affect disease expression.

Case report: Metastatic melanoma masquerading as apical hypertrophic cardiomyopathy.

Background: Cardiac tumors are usually metastatic. Melanoma is the tumor with the highest rate of cardiac metastasis. Clinicians need to be aware of the metastatic involvement of the left ventricular apex as a differential diagnosis of apical hypertrophic cardiomyopathy. Case summary: A 74-year-old woman presented for evaluation of fatigue. The initial electrocardiogram and echocardiogram showed features of apical hypertrophic cardiomyopathy. The patient reported a lesion on her right forearm that had been present for many years, leading to its biopsy, which showed melanoma. Further evaluation with a chest-computed tomography (CT) scan showed left lung nodules and nodular thickening of the left ventricular apex. Positron emission tomography showed an increased uptake of fluorodeoxyglucose in the left lung nodule and left ventricular apex, suggestive of metastatic spread of the melanoma. A CT-guided biopsy of the left lung nodule revealed melanoma. The patient was treated with ipilimumab initially, followed by paclitaxel with poor response to treatment, and later passed under hospice care. Conclusion: Metastatic tumors involving the left ventricular apex should be considered in the differential diagnosis of apical hypertrophic cardiomyopathy, especially in patients with a history of melanoma, and advanced cardiac imaging, including cardiac magnetic resonance imaging, CT, and/or positron emission tomography (PET) may help with narrowing down the differential diagnosis.

An Unusual Genetic Observation in a Case of Short-Coupled PVC-Triggered Ventricular Fibrillation.

Ventricular fibrillation induced by short-coupled premature ventricular complex is an uncommon cause of cardiac arrest in young individuals with no structural heart disease. The genetic substrate of this condition is heterogeneous and remains incompletely defined. We describe a case of short-coupled premature ventricular complex-triggered ventricular fibrillation with a likely pathogenic variant in the titin (TTN) gene. (Level of Difficulty: Advanced.).

Aging-associated susceptibility to stress-induced ventricular arrhythmogenesis is attenuated by tetrodotoxin.

Aging is associated with increased prevalence of life-threatening ventricular arrhythmias, but mechanisms underlying higher susceptibility to arrhythmogenesis and means to prevent such arrhythmias under stress are not fully defined. We aimed to define differences in aging-associated susceptibility to ventricular fibrillation (VF) induction between young and aged hearts. VF induction was attempted in isolated perfused hearts of young (6-month) and aged (24-month-old) male Fischer-344 rats by rapid pacing before and following isoproterenol (1 µM) or global ischemia and reperfusion (I/R) injury with or without pretreatment with low-dose tetrodotoxin, a late sodium current blocker. At baseline, VF could not be induced; however, the susceptibility to inducible VF after isoproterenol and spontaneous VF following I/R was 6-fold and 3-fold higher, respectively, in old hearts (P < 0.05). Old animals had longer epicardial monophasic action potential at 90% repolarization (APD90; P < 0.05) and displayed a loss of isoproterenol-induced shortening of APD90 present in the young. In isolated ventricular cardiomyocytes from older but not younger animals, 4-aminopyridine prolonged APD and induced early afterdepolarizations (EADs) and triggered activity with isoproterenol. Low-dose tetrodotoxin (0.5 µM) significantly shortened APD without altering action potential upstroke and prevented 4-aminopyridine-mediated APD prolongation, EADs, and triggered activity. Tetrodotoxin pretreatment prevented VF induction by pacing in isoproterenol-challenged hearts. Vulnerability to VF following I/R or catecholamine challenge is significantly increased in old hearts that display reduced repolarization reserve and increased propensity to EADs, triggered activity, and ventricular arrhythmogenesis that can be suppressed by low-dose tetrodotoxin, suggesting a role of slow sodium current in promoting arrhythmogenesis with aging.

Atrial Fibrillation Management: A Comprehensive Review with a Focus on Pharmacotherapy, Rate, and Rhythm Control Strategies.

Atrial fibrillation (AF) is an increasingly common arrhythmia encountered in clinical practice that leads to a substantial increase in utilization of healthcare services and a decrease in the quality of life of patients. The prevalence of AF will continue to increase as the population ages and develops cardiac comorbidities; thus, prompt and effective treatment is important to help mitigate systemic resource utilization. Treatment of AF involves two tenets: prevention of stroke and systemic embolism and symptom control with either a rate or a rhythm control strategy. Historically, due to the safe nature of medications like beta-blockers and non-dihydropyridine calcium channel blockers, used in rate control, it has been the initial strategy used for symptom control in AF. Newer data suggest that a rhythm control strategy with antiarrhythmic medications with or without catheter ablation may lead to a reduction in major adverse cardiovascular events, particularly in patients newly diagnosed with AF. Modulation of factors that promote AF or its complications is another important aspect of the overall holistic management of AF. This review provides a comprehensive focus on the management of patients with AF and an in-depth review of pharmacotherapy of AF in the rate and rhythm control strategies.

In adults aged 75 to 76 y, systematic AF screening reduced morbidity and mortality at 6 y.

SOURCE CITATION: Svennberg E, Friberg L, Frykman V, et al. Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial. Lancet. 2021;398:1498-1506. 34469764.