Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations.

Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the ten guidelines and recommendations retrieved, seven showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced disease. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.

Response to letter to editor, re-predictors of morbidity and in-hospital mortality following procedure-related cardiac tamponade.

We had included only the patients with cardiac tamponade, excluded those coded for pericardial effusion. The feasibility of comparison of the databases of two regions needs to be evaluated. There are some inherent limitations for the studies carried out from the National In-patient Samples (NIS) database.

Predictors of morbidity and in-hospital mortality following procedure-related cardiac tamponade.

Background: Cardiac tamponade (CT) can be a complication following invasive cardiac procedures. We assessed CT following common cardiac electrophysiology (EP) procedures to facilitate risk prediction of associated morbidity and in-hospital mortality. Methods: Patients who underwent various EP procedures in the cardiac catheterization lab (ablations and device implantations) were identified using the International Classification of Diseases, Ninth and Tenth Edition, Clinical Modification (ICD-9-CM and ICD-10-CM, respectively) from the Nationwide Inpatient Sample (NIS) database. Patient demographics, presence of comorbidities, CT-related events, and in-hospital death were also abstracted from the NIS database. Results: The frequency of CT-related events in patients with EP intervention from 2010 to 2017 ranged from 3.4% to 7.0%. In-hospital mortality related to CT-related events was found to be 2.2%. Increasing age was the only predictor of higher mortality in atrial fibrillation (AF) ablation and cardiac resynchronization therapy (CRT) groups (OR [95% CI]: AF ablation = 11.15 [1.70-73.34], p = .01; CRT = 1.41 [1.05-1.90], p = .02). Conclusions: In the real-world setting, CT-related events in EP procedures were found to be 3.4%-7.0% with in-hospital mortality of 2.2%. Older patients undergoing AF ablation were found to have higher mortality.

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives.

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea.

Objective: Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA. Methods: Newly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality. Results: In cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69-0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05-1.31) and women (OR 1.26, 95% CI 1.10-1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5-8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05-1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality. Conclusion: The implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized.

Interpreting Incidentally Identified Variants in Genes Associated With Heritable Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Rapid advances in genetic technologies have led to expanding use of diagnostic, research, and direct-to-consumer exome and genome sequencing. Incidentally identified variants from this sequencing represent a significant and growing challenge to interpret and translate into clinical care and include variants in genes associated with heritable cardiovascular disease such as cardiac ion channelopathies, cardiomyopathies, thoracic aortic disease, dyslipidemias, and congenital/structural heart disease. These variants need to be properly reported, the risk of associated disease accurately assessed, and clinical management implemented to prevent or lessen the disease so that cardiovascular genomic medicine can become both predictive and preventive. The goal of this American Heart Association consensus statement is to provide guidance to clinicians who are called on to evaluate patients with incidentally identified genetic variants in monogenic cardiovascular disease genes and to assist them in the interpretation and clinical application of variants. This scientific statement outlines a framework through which clinicians can assess the pathogenicity of an incidental variant, which includes a clinical evaluation of the patient and the patient's family and re-evaluation of the genetic variant in question. Furthermore, this guidance underscores the importance of a multidisciplinary team to address these challenging clinical evaluations and highlights how clinicians can effectively interface with specialty centers.

Impact of Cardiac Implantable Electronic Devices on Cost and Length of Stay in Patients With Surgical Aortic Valve Replacement and Transcutaneous Aortic Valve Implantation.

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in aortic stenosis are associated with arrhythmic complications that can require cardiac implantable electronic device (CIED) implantation, but impact on healthcare-associated cost (HAC) and length of stay (LOS) are unknown. This study aimed to assess differences among SAVR/TAVI patients with CIED implantation on HAC and LOS. Patients hospitalized for SAVR or TAVI between 2011 and 2017 on the National Inpatient Sample database were identified and stratified according to presence/type of CIED implantation. During this period, 95,262 patients were identified; 6,435 (6.8%) patients received CIED (median [interquartile range] age: 74.0 [66.0 to 82.0] years). The median adjusted HAC was $44,271 and LOS was 6 days. CIED implantation was associated with longer LOS and higher adjusted HAC in patients with SAVR and TAVI (p <0.0001). Patients with in-hospital death and complications because of SAVR or TAVI had longer preceding in-hospital days of admission. Male patients admitted to small hospitals and the West region had the highest HAC. In conclusion, CIED implantation for arrhythmias results in higher HAC and longer LOS in patients with aortic stenosis for both SAVR and TAVI.

Accelerated Aging in LMNA Mutations Detected by Artificial Intelligence ECG-Derived Age.

OBJECTIVE: To demonstrate early aging in patients with lamin A/C (LMNA) gene mutations after hypothesizing that they have a biological age older than chronological age, as such a finding impacts care. PATIENT AND METHODS: We applied a previously trained convolutional neural network model to predict biological age by electrocardiogram (ECG) [Artificial Intelligence (AI)-ECG age] to LMNA patients evaluated by multiple ECGs from January 1, 2003, to December 31, 2019. The age gap was the difference between chronological age and AI-ECG age. Findings were compared with age-/sex-matched controls. RESULTS: Thirty-one LMNA patients who had a total of 271 ECGs were studied. The median age at symptom onset was 22 years (range, <1-53 years; n=23 patients); eight patients were asymptomatic family members carrying the LMNA mutation. Cardiac involvement was detected by ECG and echocardiogram in 16 patients and consisted of ventricular arrhythmias (13), atrial fibrillation (12), and cardiomyopathy (6). Four patients required cardiac transplantation. Fourteen patients had neurological manifestations, mainly muscular dystrophy. LMNA mutation carriers, including asymptomatic carriers, were 16 years older by AI-ECG than non-LMNA carriers, suggesting accelerated biological age. Most LMNA patients had an age gap of more than 10 years, compared with controls (P<.001). Consecutive AI-ECG analysis showed accelerated aging in the LMNA group compared with controls (P<.0001). There were no significant differences in age-gap among LMNA patients based on phenotype. CONCLUSION: AI-ECG predicted that LMNA patients have a biological age older than chronological age and accelerated aging even in the absence of cardiac abnormalities by traditional methods. Such a finding could translate into early medical intervention and serve as a disease biomarker.

Trends, Burden, and Impact of Arrhythmias on Cardiac Transplant Recipients: A 16-year Nationwide Study.

Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and allograft rejection may result in an increased prevalence of arrhythmias in transplanted hearts. We aim to describe the trends, distribution, and the clinical impact of arrhythmias in patients with transplanted hearts. We queried the National Inpatient Sample with administrative codes for cardiac transplant patients using procedure ICD-9-CM codes 37.5 and 33.6. Arrhythmias were extracted using validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis. There were a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States of which 1,6342 (54.4%) had an arrhythmia. The frequency of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. Transplant patients with arrythmias was not associated with significantly higher inpatient mortality (7.72% vs 6.90%, P = 0.225). The most common arrythmia was atrial fibrillation ([AF]26.83%) followed by ventricular tachycardia (22.86%). Trends in mortality associated with arrhythmias following heart transplant has been decreasing from 12.3% in 1999 to 8.9% in 2014 (P = 0.04). Subgroup analysis of ventricular arrythmias (VA) following heart transplant were associated with increased mortality (8.61% vs 6.94%, P = 0.0229). Over half of patients develop 1 or more cardiac arrhythmia after heart transplant. There is an increasing secular trend in the frequency of arrhythmias post cardiac transplant with atrial fibrillation determined to be the most common arrhythmia.

Impact of Atrial Fibrillation on Outcomes of Aortic Valve Implantation.

New or preexisting atrial fibrillation (AF) is frequent in patients undergoing aortic valve replacement. We evaluated whether the presence of AF during transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) impacts the length of stay, healthcare adjusted costs, and inpatient mortality. The median length of stay in the patients with AF increased by 33.3% as compared with those without AF undergoing TAVI and SAVR (5 [3 to 8] days vs 3 [2 to 6] days, p <0.0001 and 8 [6 to 12] days vs 6 [5 to 10] days, p <0.0001, respectively). AF increased the median value of adjusted healthcare associated costs of both TAVI ($46,754 [36,613 to 59,442] vs $49,960 [38,932 to 64,201], p <0.0001) and SAVR ($40,948 [31,762 to 55,854] vs $45,683 [35,154 to 63,026], p <0.0001). The presence of AF did not independently increase the in-hospital mortality. In conclusion, in patients undergoing SAVR or TAVI, AF significantly increased the length of stay and adjusted healthcare adjusted costs but did not independently increase the in-hospital mortality.

Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and "brain fog". Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.

Special Article - The role of hand-held ultrasound for cardiopulmonary assessment during a pandemic.

During the COVID-19 pandemic, we are likely to see a significant increase in the requests for rapid assessment of cardiac function, due to the frequent pre-existence of cardiac pathologies in patients admitted to hospital, and to the emergence of specific cardiac manifestations of this infection, such as myocarditis, sepsis related cardiomyopathy, stress induced cardiomyopathy and acute coronary syndromes. Hand-held, point-of-care ultrasound (HH-POCUS) is particularly suited for the provision of rapid, focused, integrated assessments of the heart and lungs. We present a review of the indications and protocols for focused HH-POCUS use in an acute setting and formulate proposals for streamlining their application in the COVID-19 context towards guiding optimum management of these patients while at the same time allowing adherence to robust infection control measures to provide safety to both the patient and our clinical staff.

COVID-19 and cardiac arrhythmias.

BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVES: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.

Atrial fibrillation is not an independent predictor of outcome in patients with aortic stenosis.

OBJECTIVES: To examine the prognostic significance of atrial fibrillation (AF) versus sinus rhythm (SR) on the management and outcomes of patients with severe aortic stenosis (AS). METHODS: 1847 consecutive patients with severe AS (aortic valve area ≤1.0 cm2 and aortic valve systolic mean Doppler gradient ≥40 mm Hg or peak velocity ≥4 m/s) and left ventricular ejection fraction ≥50% were identified. The independent association of AF and all-cause mortality was assessed. RESULTS: Age was 76±11 years and 46% were female; 293 (16%) patients had AF and 1554 (84%) had SR. In AF, 72% were symptomatic versus 71% in SR. Survival rate at 5 years for AF (41%) was lower than SR (65%) (age- and sex-adjusted HR=1.66 (1.40-1.98), p<0.0001). In multivariable analysis, factors associated with mortality included age (HR per 10 years=1.55 (1.42-1.69), p<0.0001), dyspnoea (HR=1.58 (1.33-1.87), p<0.0001), ≥ moderate mitral regurgitation (HR=1.63 (1.22-2.18), p=0.001), right ventricular systolic dysfunction (HR=1.88 (1.52-2.33), p<0.0001), left atrial volume index (HR per 10 mL/m2=1.13 (1.07-1.19), p<0.0001) and aortic valve replacement (AVR) (HR=0.44 (0.38-0.52), p<0.0001). AF was not a predictor of mortality independent of variables strongly correlated HR=1.02 (0.84-1.25), p=0.81). The 1-year probability of AVR following diagnosis of severe AS was lower in AF (49.8%) than SR (62.5%) (HR=0.73 (0.62-0.86), p<0.001); among patients with AF not referred for AVR, symptoms were frequently attributed to AF instead of AS. CONCLUSION: AF was associated with poor prognosis in patients with severe AS, but apparent differences in outcomes compared with SR were explained by factors other than AF including concomitant cardiac abnormalities and deferral of AVR due to attribution of cardiac symptoms to AF.

Effect of Adaptive Servo-Ventilation on Periodic Limb Movements in Sleep in Patients With Heart Failure.

Periodic limb movements in sleep (PLMS) are associated with adverse outcomes in patients with heart failure (HF). The aim of this study was to investigate whether PLMS change in response to adaptive servo-ventilation (ASV) for central sleep apnea (CSA) in patients with HF. We examined polysomnographic studies conducted between 2010 and 2014 at Mayo Clinic, Rochester, Minnesota (n = 14,444). In those, 314 of 579 patients with CSA completed the sleep study with a protocol that began with diagnostic polysomnography, followed by continuous positive airway pressure, and, for persistent CSA, by ASV titration. Patients with HF (n = 118) had a significantly higher median PLM index compared with those without HF (n = 196): 33.7 versus 6.1 events/h (p <0.001). HF was associated with a significant PLM arousal index (PLMAI) increase from diagnostic trial to ASV (odds ratio [OR]  = 1.79, p = 0.032) after adjusting for demographics, co-morbidities and medications. In patients aged >68 years, HF was associated with PLMI and PLMAI increases during ASV (OR  = 2.16, p = 0.016 and OR  = 2.05, p = 0.024), which persisted in multivariable models (OR  = 2.36, p = 0.025 and OR  = 2.33, p = 0.026). In multivariable analysis, patients with ejection fraction ≤45% had higher odds of increased PLMAI during ASV than those with ejection fraction >45% (OR  = 1.98, p = 0.022). In conclusion, PLMS may increase in HF patients after suppression of CSA by ASV. Whereas the clinical significance of increased post-ASV PLMS in HF prognosis needs to be determined, these increases may contribute to worsening outcomes in HF patients with CSA treated with ASV.

Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy.

OBJECTIVE: We aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP). METHODS: We prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea-Sleep Disorders Questionnaire (SA-SDQ) and STOP-BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP-7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed-rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP-7 scores. RESULTS: Thirty-five percent of patients had pOSA, with a mean ODI of 11.3 ± 5.1/h (range = 5.1-22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA-SDQ and STOP-BAG scores (all P < 0.05). Median rSUDEP-7 score was 3 ± 1.4 (range = 0-6). Higher rSUDEP-7 scores were positively correlated with higher ODI (P = 0.036). rSUDEP-7 score ≥ 5 was associated with pOSA by ODI, SA-SDQ, and STOP-BAG questionnaire criteria (P < 0.05). SIGNIFICANCE: Our pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.

International survey of knowledge, attitudes, and practices of cardiologists regarding prevention and management of cardiac implantable electronic device infections.

BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) can be life-saving. However, complications from CIED infection can be life-threatening, often requiring device removal. Despite publication of CIED infection management guidelines, there remains marked variation in clinical practice. OBJECTIVE: To better understand and quantify these differences, we conducted a multinational survey of practitioners of CIED management. METHODS: An electronic survey was sent to Heart Rhythm Society members, spanning 70 countries across six continents. All responses were collected anonymously. RESULTS: 227 out of 3,600 (6.3%) responded to the survey. The majority of surveys were completed by practitioners from the United States (168; 68.3%) and 53.8% of these practiced in academic medical centers. The large majority (92.7%) of sites had protocols to ensure appropriate timing of prophylactic antibiotics. Superficial (incisional) site infections were treated with antibiotics alone 52.5% of the time (consistent with guidelines); in contrast, deep pocket infections were treated with antibiotics (with device removal) in accordance to guidelines only 37.4% of the time. Almost all providers (98.7%) were inclined to perform complete hardware removal in cases of CIED-related endocarditis. In contrast, 82.2% of survey participants suggested complete CIED system removal in patients with an occult Gram-positive bacteremia, 65.5% with occult Gram-negative bacteremia, and 59.3% with prolonged bacteremia due to a source other than CIED. CONCLUSIONS: These data suggest wide variability in clinical practice in managing CIED infection with significant deviations from published guidelines. There is critical need to increase awareness and develop institutional protocols to ensure adherence with evidence-based guidelines to optimize outcomes.