Targeted left ventricular lead positioning to the site of latest activation in cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.

Non-vitamin K oral anticoagulants versus warfarin for left atrial appendage thrombus resolution in nonvalvular atrial fibrillation or flutter.

BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) have emerged as alternatives to vitamin K antagonists in select situations. For left atrial (LA) appendage thrombus in nonvalvular atrial fibrillation (AF) or flutter, guidelines recommend oral anticoagulation (OAC) for at least 3 weeks prior to reassessment. Data comparing NOACs to warfarin in this scenario are scarce. METHODS: A retrospective study identified subjects with nonvalvular AF or flutter who were: a) noted to have LA thrombus detected on transesophageal echocardiography (TEE), b) previously not receiving long-term OAC; and c) evaluated for resolution of LA thrombus by follow-up TEE between 3 weeks to less than 1 year of the initial TEE. RESULTS: The study included 45 subjects with mean age 63.2 years, 69% male, 78% white race/ethnicity, 42% paroxysmal, and mean CHA2 DS2 -VASc score 3.4 ± 1.7. All LA thrombi were confined to the appendage. OAC received included apixaban (3), dabigatran (13), rivaroxaban (6), and warfarin (23), The median follow-up time to repeat TEE was 67 (interquartile range, 49-96) days. LA appendage thrombus resolution rates were 76% for the entire cohort, 77% for NOACs, and 74% for warfarin. In univariable logistic regression analysis, LA appendage thrombus resolution was similar for NOACs when compared to warfarin (odds ratio, 1.20; 95% confidence interval, 0.31-4.69; P = .79). CONCLUSIONS: In patients nonvalvular AF or flutter who were OAC naïve at the time of diagnosis with LA appendage thrombus, complete resolution was similar between NOACs and warfarin.

Sex-specific clinical outcomes after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Sex differences in clinical outcomes for left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) after cardiac resynchronization therapy (CRT) are not well described. METHODS: A retrospective cohort study at an academic medical center included subjects with LBBB-associated idiopathic NICM who received CRT. Cox regression analyses estimated the hazard ratios (HRs) between sex and clinical outcomes. RESULTS: In 123 total subjects (mean age 62 years, mean initial left ventricular ejection fraction 22.8%, 76% New York Heart Association class III, and 98% CRT-defibrillators), 55 (45%) were men and 68 (55%) were women. The median follow-up time after CRT was 72.4 months. Similar risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate antitachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) was observed between men and women (HR, 1.20; 95% confidence interval [CI] 0.57-2.51; p = 0.63). This persisted in multivariable analyses. Men and women had similar risk for all-cause mortality in univariable analysis, but men had higher risk in the final multivariable model that adjusted for age at diagnosis, QRS duration, and left ventricular end-diastolic dimension index (HR, 4.55; 95% CI, 1.26-16.39; p = 0.02). The estimated 5-year mortality was 9.5% for men and 6.9% for women. CONCLUSIONS: In LBBB-associated idiopathic NICM, men have higher risk for all-cause mortality after CRT when compared to women.

Myocardial recovery after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Baseline predictors of myocardial recovery after cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) are unknown. METHODS: A retrospective study included subjects with idiopathic NICM, left ventricular ejection fraction (LVEF) ≤35%, and LBBB. Myocardial recovery was defined as post-CRT LVEF ≥50%. Logistic regression analyses described associations between baseline characteristics and myocardial recovery. Cox regression analyses estimated the hazard ratio (HR) between myocardial recovery status and adverse clinical events. RESULTS: In 105 subjects (mean age 61 years, 44% male, mean initial LVEF 22.6% ± 6.6%, 81% New York Heart Association class III, and 98% CRT-defibrillators), myocardial recovery after CRT was observed in 56 (54%) subjects. Hypertension, heart rate, and serum blood urea nitrogen (BUN) had negative associations with myocardial recovery in univariable analyses. These associations persisted in multivariable analysis: hypertension (odds ratio (OR), 0.40; 95% confidence interval (CI), 0.17-0.95; p = 0.04), heart rate (OR per 10 bpm, 0.69; 95% CI, 0.48-0.997; p = 0.048), and serum BUN (OR per 1 mg/dl, 0.94; 95% CI, 0.88-0.99; p = 0.04). Subjects with post-CRT LVEF ≥50%, when compared to <50%, had lower risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate anti-tachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) over a median follow-up of 75.9 months (HR, 0.38; 95% CI, 0.16-0.88; p = 0.02). CONCLUSION: In LBBB-associated idiopathic NICM, myocardial recovery after CRT was associated with absence of hypertension, lower heart rate, and lower serum BUN. Those with myocardial recovery had fewer adverse clinical events.

New-onset left bundle branch block-associated idiopathic nonischemic cardiomyopathy and time from diagnosis to cardiac resynchronization therapy: The NEOLITH II study.

BACKGROUND: The optimal timing for cardiac resynchronization therapy (CRT) after diagnosis of new-onset left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) and treatment with guideline-directed medical therapy (GDMT) is unknown. The purpose of this study was to describe relationships between time from diagnosis to CRT and outcomes in new-onset LBBB-associated idiopathic NICM with left ventricular ejection fraction (LVEF) ≤35%. METHODS: A retrospective cohort study examined associations between time from diagnosis to CRT (≤9 months vs >9 months) and clinical and echocardiographic outcomes. RESULTS: In 123 subjects with LBBB-associated idiopathic NICM, time from diagnosis to CRT was ≤9 months in 60 (49%) subjects and 9 months in 63 (51%) subjects. Clinical outcomes were similar for those implanted ≤9 months versus >9 months for adverse clinical events (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.41-1.78; P = 0.67) and all-cause mortality (HR, 0.57; 95% CI, 0.19-1.70; P = 0.31). Multivariable analyses demonstrated similar results. In 105 subjects with post-CRT echocardiograms, LVEF improvement to >35% was more likely in those implanted ≤9 months when compared to >9 months (odds ratio [OR], 3.53; 95% CI, 1.32-9.46; P = 0.01). This association persisted in the final multivariable model adjusted for age at diagnosis, sex, QRS duration, post-GDMT LVEF, and time from CRT to post-CRT echocardiogram (OR, 5.10; 95% CI, 1.71-15.22; P = 0.004). CONCLUSION: In LBBB-associated idiopathic NICM, earlier CRT implantation was associated with more favorable cardiac remodeling. Delaying CRT may miss a critical period to halt and reverse progressive myocardial damage.

Oral anticoagulation and left atrial thrombi resolution in nonrheumatic atrial fibrillation or flutter: A systematic review and meta-analysis.

BACKGROUND: Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS: Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and < 1 year, were selected. Study quality was assessed using recommendations adapted from the Agency for Healthcare Research and Quality. Pooled LAT resolution rates were evaluated for vitamin K antagonist (VKA) studies and low risk of bias warfarin studies. RESULTS: The pooled LAT resolution rate of 619 subjects from 16 VKA studies was 63.7% (95% confidence interval [CI], 53.3%-72.9%). The pooled LAT resolution rate of 94 subjects from four studies that specified warfarin use, exclusion of prior long-term therapeutic OAC, and target international normalized ratio (INR) ≥ 2.0 and/or average achieved INR ≥ 2.0 was 79.3% (95% CI, 69.8%-86.4%). Two studies in direct-acting oral anticoagulants (DOACs) reported LAT resolution rates of 89.5% (17 of 19) for dabigatran and 41.5% (22 of 53) for rivaroxaban. CONCLUSIONS: Warfarin is the most studied initial OAC agent for treating LAT in nonrheumatic AF and/or AFL with a resolution rate of nearly 80%. Further studies in DOACs are warranted.

Predictors and implications of early left ventricular ejection fraction improvement in new-onset idiopathic nonischemic cardiomyopathy with narrow QRS complex: A NEOLITH substudy.

BACKGROUND: Predictors and implications of early left ventricular ejection fraction (LVEF) improvement with guideline-directed medical therapy (GDMT) in new-onset idiopathic nonischemic cardiomyopathy (NICM) with narrow QRS complex are not well described. The objectives were to describe predictors of LVEF improvement after 3 months on GDMT and adverse cardiac events based on post-GDMT LVEF status (≤35% vs. >35%). METHODS: A retrospective cohort study was performed in subjects with new-onset NICM, LVEF ≤35%, and narrow QRS complex. Associations for baseline variables with post-GDMT LVEF improvement and absolute change in LVEF (∆LVEFGDMT ) were assessed. Cox proportional hazards models assessed associations for post-GDMT LVEF status with adverse cardiac events. RESULTS: In 70 subjects, 31 (44%) had post-GDMT LVEF ≤35% after a median follow-up time of 97.5 days (interquartile range, 84-121 days). In final multivariable models, severely dilated left ventricular end-diastolic diameter (LVEDD), compared with normal LVEDD, strongly predicted post-GDMT LVEF ≤35% (odds ratio, 7.77; 95% confidence interval [CI], 1.39-43.49; p = .02) and ∆LVEFGDMT (ß = -15.709; standard error = 4.622; p = .001). Subjects with post-GDMT LVEF ≤35% were more likely to have adverse cardiac events over a median follow-up time of 970.5 days (unadjusted hazard ratio, 2.15; 95% CI, 0.93-4.96; p = .07). In the post-GDMT LVEF ≤35% group, 9 of 26 subjects (35%) had long-term LVEF > 35%. CONCLUSION: In new-onset NICM with narrow QRS complex, nondilated LVEDD predicted early LVEF improvement. Those with post-GDMT LVEF ≤35% had higher risk of adverse cardiac events, but a substantial proportion demonstrated continued long-term LVEF improvement.

Provider Response to QTc Prolongation on Standard 12-Lead EKG: Do We Notice or Do We Care?

BACKGROUND: Drugs and electrolyte imbalances are widely recognized as common triggers of a prolonged QT interval. We conducted a chart review to assess provider response to prolonged QT reported on a standard 12-lead electrocardiogram (EKG). METHODS: We identified all Veterans Affairs Pittsburgh Healthcare System patients in a 6-month period with an EKG reporting a corrected QT (QTc) >500 ms. We excluded confounding or uninterpretable EKGs. Charts were reviewed to assess medications and electrolytes at the time of the EKG as well as the setting (inpatient vs outpatient) in which the EKG was obtained. Provider documentation of QTc and any corrective measures were sought. RESULTS: After exclusions, 106 patients were included in this analysis (87 [82%] inpatient and 19 [18%] outpatient). Most were male (101, 95%) with a mean age of 63.5 ± 10.6 years. At the time of index EKG, most patients were receiving at least one (72, 68%), and frequently two or more (35, 33%), QTc prolonging medications. Providers documented QTc prolongation in 20 inpatients (19%). Drugs were adjusted or discontinued in only two inpatients (2%). There were 14 patients (14%) with potassium level <3.6 mmol/L and 10 of 69 (14%) patients had a magnesium level <1.7 mg/dL. CONCLUSION: Patients with prolonged QTc on EKG were more likely to be inpatients than outpatients. Inpatients were more likely to be receiving multiple types and classes of QTc prolonging medications. In the vast majority of cases, providers did not address the prolonged QTc and only rarely initiated remedial actions.

Characteristics and Outcomes of Concurrently Diagnosed New Rapid Atrial Fibrillation or Flutter and New Reduced Ejection Fraction.

BACKGROUND: Characteristics and outcomes of concurrently diagnosed new rapid atrial fibrillation (AF) or atrial flutter (AFL) and new heart failure with reduced left ventricular ejection fraction (LVEF) are not well described. METHODS: A retrospective cohort study of subjects referred for expedited transesophageal echocardiography-guided rhythm-control strategies for concurrent new rapid AF/AFL and new LVEF ≤ 40% diagnosed during the same admission was analyzed. RESULTS: Twenty-five subjects (median age 57 years; 96% male; 96% Caucasian; median CHA2 DS2 -VASc = 2) presented with new AF (n = 18) or AFL (n = 7) with rapid ventricular rate (median 135 beats/min) and new reduced LVEF (median 27%; range, 10-37.5%). Seven (28%) subjects had left atrial appendage thrombi (LAAT) and five (20%) subjects had heavy or binge alcohol use. Baseline characteristics were similar between those with and without LAAT. Thirteen subjects with AF and without LAAT underwent direct-current cardioversion (DCCV) and 10 (77%) had AF recurrence within 90 days. Improvement of long-term LVEF to >40% was comparable for subjects with and without initial LAAT (83% vs 94%; P = 0.46). Three of four subjects who received primary prophylaxis implantable cardioverter-defibrillators improved their LVEF to >35% after sinus rhythm maintenance. The median long-term follow-up time was 3.0 years. CONCLUSIONS: Subjects with concurrently diagnosed new rapid AF/AFL and new reduced LVEF are characterized by a high prevalence of LAAT and significant alcohol use. AF subjects without initial LAAT who underwent DCCV had a high 90-day AF recurrence rate. The presence of LAAT did not have a prognosticative effect on eventual LVEF improvement, which was observed in almost all subjects.

Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as a Standard of Care for Cardiac Implantable Electronic Device Implantation.

INTRODUCTION: Infection of cardiac implanted electrical devices (CIED) is a problem. In selected patients, use of an "antibacterial envelope" (AIGISRx®) is associated with low CIED infection rates. The value of this device when used as a standard of care is unclear. METHODS AND RESULTS: Retrospective analysis of all patients (N = 1,476) who underwent CIED implantation at a single hospital. During the study period, some implanters used the AIGISRx as a standard of care (Yes-AIGISRx Group, N = 365), whereas others did not use it at all (No-AIGISRx Group, N = 1,111). A risk score based on preoperative factors was calculated for each patient. Rates of CIED infection within 6 months were measured, and associated costs were estimated. The Yes-AIGISRx and No-AIGISRx groups had similar preoperative infection risk. In the No-AIGISRx group, 19 infections were observed (1.7%), versus 0 in the Yes-AIGISRx group (P = 0.006). The 6-month mortality rate among patients with infection was significantly greater than among those without infection (15.7% vs. 4.5%, P = 0.021). The average hospital duration for infection care was 13 days. By extrapolating the infection rate and costs observed in the No-AIGISRx group to the Yes-AIGISRx group, we estimated that there would have been 6.2 additional infections costing approximately $340,000. This cost was similar to the actual cost of the devices in the Yes-AIGISRx group, estimated at $320,000. CONCLUSIONS: Standard of care use of an antibacterial envelope as a standard of care was associated with a significantly lower rate of CIED infection, and appeared to be economically reasonable. Prospective trials to address these findings may be worthwhile.

Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients.

BACKGROUND: We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. METHODS: At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. RESULTS: A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). CONCLUSION: Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.

Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.

AIM OF THE STUDY: Complement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti-tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism in CFH gene with lung cancer and the interaction with cigarette smoking. MATERIAL AND METHODS: This case-control study included 80 primary lung cancer patients and 106 control subjects who were genotyped for Try402His (rs1061170) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Variant genotypes (Tyr/His and His/His) were overpresented among patients compared to controls (p = 0.03, OR = 2.510, 95% CI: 1.068-5.899), and the frequency of variant H allele was significantly overexpressed in cases compared to controls (p = 0.021). Tyr/His genotype was identified in 100% of small cell lung cancer (SCLC) patients vs. 34.5% of non-SCLC (NSCLC), while 20.7% of NSCLC patients were homozygous for the variant allele (His/His) (p = 0.001). Binary logistic regression analysis revealed a 2.5 times greater estimated risk for NSCLC than for SCLC among variant allele carriers, and a 7.3-fold increased risk of lung cancer among variant allele smoking carriers vs. 1.3-fold increased risk among wild allele smoking carriers. Moreover, the stage of cancer positively correlated with smoking and pack-years in allele H carriers, and the correlation was stronger among those who were homozygous for it (His/His) than those who were heterozygous (Tyr/His). CONCLUSIONS: CFH 402H variant is a smoking-related risk factor for lung cancer, particularly the NSCLC.

Depression and outcome among veterans with implantable cardioverter defibrillators with or without cardiac resynchronization therapy capability.

BACKGROUND: The impact of depression on outcome in implantable cardioverter defibrillator (ICD) recipients has not been fully appreciated. We assessed the prevalence of depression and its association with heart failure (HF) outcome among veterans with ICDs. METHODS AND RESULTS: Patients enrolled between January 2005 and January 2010 in the Outcomes among Veterans with Implantable Defibrillators Registry were studied. We examined the cross-sectional association of depression with severity of HF functional class as well as the association of depression with the composite outcome of mortality or HF hospitalization over a mean follow-up time of 2.7 years. There were 3,862 patients enrolled. Patients with depression (1,162, 43%) were younger (63.1 ± 9.4 years vs 66.6 ± 9.9 years, P < 0.001), more likely to have a history of tobacco or alcohol abuse (P < 0.0001) or atrial fibrillation (P = 0.05) while having a higher ejection fraction (28.3% vs 27.4%, P = 0.03). Depression was associated with advanced HF class at time of implant; odds ratio (OR; vs class I) for class III: 1.65 (confidence interval [CI] 1.17-2.33), class IV: 1.73 (95% CI 1.08-2.76). Death or HF hospitalization was more likely to occur in patients with depression (35.2% vs 32.0%, HR: 1.15 [95% CI 0.99-1.33]). The predictive value of depression was stronger after multivariable adjustment; HR: 1.25 (95% CI 1.05-1.49). CONCLUSION: Depression was prevalent among veterans with ICDs. Depression was associated with severity of HF. The predictive value of associated depression was significant after multivariable adjustment.

Impact of Weight Gain on Cardiovascular Outcomes in Patients With Atrial Fibrillation.

BACKGROUND: The long-term impact of weight gain (WG) on cardiovascular outcomes among patients with atrial fibrillation (AF) is unclear. METHODS AND RESULTS: We studied 62 871 (mean age, 72±12, 43% women) adult patients with AF evaluated at the University of Pittsburgh Medical Center between January 1, 2010, and May 13, 2021. Serial body mass index, risk factors, comorbidities, and subsequent death and hospitalization were ascertained and stratified according to percentage WG (≥0% to <5%, ≥5% to <10%, and ≥10%). Over 4.9±3.19 years of follow-up, 27 114 (43%) patients gained weight (61%, ≥0% to <5%; 23%, ≥5% to <10%; 16%, ≥10%). Patients with progressive WG were incrementally younger (P<0.001) women (40%, 42%, and 47%) with lower median household income (P=0.002) and active smoking (8%, 13% and 13%), and they were less likely to be on a non-vitamin K oral anticoagulant (39%, 37%, and 32%). WG was incrementally associated with a significant increase in risk of hospitalization for AF (≥10% WG; hazard ratio [HR], 1.2 [95% CI, 1.2-1.3]; P<0.0001), heart failure (≥10% WG; HR, 1.44 [95% CI, 1.3-1.6]; P<0.001; ≥5% to <10% WG; HR, 1.17 [95% CI, 1.1-1.2]; P<0.001), myocardial infarction (≥10% WG; HR, 1.2 [95% CI, 1.3-1.6]; P<0.001) and all-cause stroke (4.2%, 4.3%, and 5.6%) despite significantly lower mean CHADS2Vasc score (2.9±1.7, 2.7±1.6, and 2.7±1.7). Patients with more WG were significantly more likely to receive cardiac and electrophysiologic interventions. CONCLUSIONS: Among patients with AF, WG is incrementally associated with increased hospitalization for cardiovascular causes, particularly heart failure, stroke, myocardial infarction, and AF.

Heart Rate at Rest and Incident Atrial Fibrillation in Patients With Diastolic Dysfunction.

Diastolic dysfunction (DD) is associated with incident atrial fibrillation (AF). The influence of heart rate at rest (RHR) on incident AF in patients with DD has not been investigated. The goal of this study is to assess the influence of RHR on incident AF in patients with DD. Patients from a large health system with no previous history of AF, a left ventricular ejection fraction ≥50%, and documented DD on echocardiography were divided into quartiles (<66, 66 to 76, 77 to 91, >91 beats per minute) based on RHR. Incident AF was estimated using AF hospitalization during follow-up. Hazard ratios (HR) for AF hospitalization and all-cause death were calculated with a Cox proportional hazards model. A total of 19,046 patients were analyzed. Over a median follow-up of 42.2 months, 742 (3.9%) patients were hospitalized for AF. Both slower and faster RHR were associated with increased risk of AF hospitalization (HR 1.40, confidence interval [CI] 1.14 to 1.71, p = 0.001, HR 1.23, CI 0.99 to 1.53, p = 0.06 and HR 1.72, CI 1.38 to 2.14, p <0.001, for quartiles 1, 2, and 4, respectively), suggesting a J-shaped relation. Progressive increase in all-cause death was noted with faster RHR (HR1.19 per quartile increase, CI 1.16 to 1.22, p <0.001). These results persisted after adjustment for age, cardiovascular co-morbidities, grade of DD, and ß-blocker use. In conclusion, this large, real-world analysis indicates increased risk of incident AF with slower and faster RHR in patients with DD. Randomized trials are needed to evaluate the potential of RHR modification to mitigate the risk of incident AF.

Patient Outcomes by Ventricular Systolic and Diastolic Function.

BACKGROUND: Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. METHODS AND RESULTS: Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF <50%, stratified by EF quartiles. Patients were followed to the end points of all-cause death and cardiovascular, HF, or cardiac arrest hospitalizations. Over a median follow-up of 3.42 years, 23 946 (16%) patients died and 31 113 (20%), 13 305 (9%), and 1269 (1%) were hospitalized for cardiovascular, HF, or cardiac arrest causes, respectively. With adjustment for comorbidities, the risk of all-cause mortality and of cardiovascular and HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF, and even more so in patients with worsening EF. The risk of hospitalization for cardiac arrest in patients with grade III DD, however, was comparable to that of patients with EF <25% (hazard ratio, 1.00 [95% CI, 0.98-1.01]) and worse than that of patients in better EF quartiles. CONCLUSIONS: Although systolic dysfunction is associated with a greater risk of overall death and HF hospitalizations than DD, the risk of cardiac arrest in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine treatment strategies than can improve these outcomes.

Evaluating circulating cell-free DNA and DNA integrity index as biomarkers in non-small cell lung cancer.

BACKGROUND: Analysis of free DNA molecules shed from tumour cells in plasma of patients referred as circulating tumour DNA (ctDNA) with reference to physiological circulating cell-free DNA (cfDNA) is nowadays exploited as liquid biopsy and is considered a new emerging promising biomarker for diagnosis, selection of proper treatment, and prognosis of cancer. DNA integrity index (DII) is assessed by calculating the ratio between the concentration of long cfDNA strands released from tumour cells (ALU247) and the short strands released from normal cells (ALU115). The aim of the current study was to evaluate DII as a potential diagnostic and prognostic biomarker of NSCLC. METHODS: Our study included 48 NSCLC patients diagnosed as primary NSCLC before starting treatment, 30 COPD patients diagnosed clinically, radiologically, and subjected to chest high-resolution computerized tomography, and 40 healthy controls. cfDNA concentration and DII were measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: ALU115, ALU247, and DII were significantly higher in NSCLC compared to COPD patients (p < 0.0001) and controls (p < 0.0001) and in COPD patients compared to control subjects (p < 0.0001). DII positively correlated with the stage of tumour (p = 0.01), tumour metastasis (p = 0.004), and with adenocarcinoma compared to other histopathological types (p = 0.02). To evaluate clinical utility of DII in NSCLC, ROC curve analysis demonstrated an AUC of 0.91 at a cut-off value of 0.44 with total accuracy = 85.6%, sensitivity = 90%, specificity = 83%, PPV = 78.1%, and NPV = 92.1%. CONCLUSION: cfDNA and DII represent a promising diagnostic and prognostic tool in NSCLC. This type of noninvasive liquid biopsy revealed its chance in the screening, early diagnosis, and monitoring of NSCLC.

Quality of Life and Type of Cardiac Resynchronization Therapy Device in Older Heart Failure Patients.

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