Abnormal left atrial body stiffness is predicted by appendage size: impact of appendage occlusion on left atrial mechanics assessed by pressure-volume analysis.

Atrial cardiomyopathy has been recognized as having important consequences for cardiac performance and clinical outcomes. The pathophysiological role of the left atrial (LA) appendage and the effect of percutaneous left atrial appendage occlusion (LAAO) upon LA mechanics is incompletely understood. We evaluated if changes in LA stiffness due to endocardial LAAO can be detected by LA pressure-volume (PV) analysis and whether stiffness parameters are associated with baseline characteristics. Patients undergoing percutaneous endocardial LAAO (n = 25) were studied using a novel PV analysis using near-simultaneous three-dimensional LA volume measurements by transesophageal echocardiography (TEE) and direct invasive LA pressure measurements. LA stiffness (dP/dV, change in pressure with change in volume) was calculated before and after LAAO. Overall LA stiffness significantly increased after LAAO compared with baseline (median, 0.41-0.64 mmHg/mL; P ≪ 0.001). LA body stiffness after LAAO correlated with baseline LA appendage size by indexed maximum depth (Spearman's rank correlation coefficient Rs = 0.61; P < 0.01). LA stiffness change showed an even stronger correlation with baseline LA appendage size by indexed maximum depth (Rs = 0.70; P < 0.001). We found that overall LA stiffness increases after endocardial LAAO. Baseline LA appendage size correlates with the magnitude of increase and LA body stiffness. These findings document alteration of LA mechanics after endocardial LAAO and suggest that the LA appendage modulates overall LA compliance.NEW & NOTEWORTHY Our study documents a correlation of LA appendage remodeling with the degree of chronically abnormal LA body stiffness. In addition, we found that LA appendage size was the baseline parameter that best correlated with the magnitude of a further increase in overall LA stiffness after appendage occlusion. These findings offer insights about the LA appendage and LA mechanics that are relevant to patients at risk for adverse atrial remodeling, especially candidates for LA appendage occlusion.

Risk and predictors of mortality after implantable cardioverter-defibrillator implantation in patients with sarcoid cardiomyopathy.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction <35%, but data on outcomes are limited. METHODS: Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine >2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59). CONCLUSION: Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.

Influence of renal function on mortality and ventricular arrhythmias in patients undergoing first implantable cardioverter-defibrillator generator replacement.

BACKGROUND: Impaired renal function is associated with increased mortality among patients with implantable cardioverter-defibrillators (ICDs). The relationship between renal function at time of ICD generator replacement and subsequent appropriate ICD therapies is not known. METHODS AND RESULTS: We identified 441 patients who underwent first ICD generator replacement between 2000 and 2011 and had serum creatinine measured within 30 days of their procedure. Patients were divided into tertiles based on estimated glomerular filtration rate (eGFR). Adjusted Cox proportional hazard and competing risk models were used to assess relationships between eGFR and subsequent mortality and appropriate ICD therapy. Median eGFR was 37.6, 59.3, and 84.8 mL/min/1.73 m(2) for tertiles 1-3, respectively. Five-year Kaplan-Meier survival probability was 34.8%, 61.4%, and 84.5% for tertiles 1-3, respectively (P < 0.001). After multivariable adjustment, compared to tertile 3, worse eGFR tertile was associated with increased mortality (HR 2.84, 95% CI [1.36-5.94] for tertile 2; HR 3.84, 95% CI [1.81-8.12] for tertile 1). At 5 years, 57.0%, 58.1%, and 60.2% of patients remained free of appropriate ICD therapy in tertiles 1-3, respectively (P = 0.82). After adjustment, eGFR tertile was not associated with future appropriate ICD therapy. Results were unchanged in an adjusted competing risk model accounting for death. CONCLUSIONS: At time of first ICD generator replacement, lower eGFR is associated with higher mortality, but not with appropriate ICD therapies. The poorer survival of ICD patients with reduced eGFR does not appear to be influenced by arrhythmia status, and there is no clear proarrhythmic effect of renal dysfunction, even after accounting for the competing risk of death.

Chemotherapy-induced cardiomyopathy.

Cardiomyopathy is an adverse outcome of antineoplastic drug therapy that has become increasingly relevant in the management of cancer survivors. As the efficacy of anticancer treatments has improved, long-term outcomes are altered by the development of cardiotoxicity, which may be associated with an even worse prognosis than that of the underlying malignancy. From the research into mechanisms, prevention, and treatment, the specialized field of cardio-oncology has evolved, but the recognition and appropriate management of these patients is important for the general internist and general cardiologist as well. Although antineoplastic chemotherapy can cause multiple forms of cardiotoxicity, including arrhythmia, pericardial disease, valvular dysfunction, and myocardial ischemia, in this review we will focus on chemotherapeutic agents associated with cardiomyopathies, from the anthracyclines to newer, the so-called targeted agents such as tyrosine kinase inhibitors. We also review the diagnostic modalities for chemotherapy-induced cardiomyopathy as well as the prevention and treatment strategies which may prolong the lives of those suffering from cancer.

Impact of Preprocedure Imaging for Left Atrial Appendage Occlusion: Insights From the NCDR LAAO Registry.

BACKGROUND: The impact of preprocedure imaging on the safety and effectiveness of left atrial appendage occlusion (LAAO) remains unclear. OBJECTIVES: This study sought to determine the rates of use of preprocedure computed tomography (CT)/cardiac magnetic resonance (CMR) and its association with safety and effectiveness of LAAO procedures. METHODS: The National Cardiovascular Data Registry LAAO Registry was used to evaluate patients who underwent attempted LAAO with the WATCHMAN and WATCHMAN FLX devices between January 1, 2016, and June 30, 2021. Safety and effectiveness of LAAO procedures was compared by use vs nonuse of preprocedural CT/CMR. Outcomes of interest included implantation success (deployment and release of device), device success (device released with peridevice leak <5 mm), and procedure success (device released with peridevice leak <5 mm and no in-hospital major adverse events [MAE]). Multivariable logistic regression was used to assess the relationship between preprocedure imaging and outcomes. RESULTS: Preprocedure CT/CMR was used for 18.2% (n = 20,851) of the 114,384 procedures in this study. CT/CMR use was more common among government and university hospitals and hospitals in the Midwest and South; it was less common among patients with uncontrolled hypertension, with abnormal renal function, and without prior thromboembolism. Overall rates of implantation success, device success, and procedure success were 93.4%, 91.2%, and 89.4%, respectively. Preprocedure CT/CMR was independently associated with an increased likelihood of implantation success (OR: 1.08; 95% CI: 1.00-1.17), device success (OR: 1.10; 95% CI: 1.04-1.16), and procedural success (OR: 1.07; 95% CI: 1.02-1.13). MAE were uncommon (2.3%) and not associated with use of preprocedure CT/CMR (OR: 1.02; 95% CI: 0.92-1.12). CONCLUSIONS: Preprocedure CT/CMR was associated with an increased likelihood of successful LAAO implantation; however, the magnitude of benefit appears small and it was not associated with MAE.

Self-reported colorectal cancer screening of Medicare beneficiaries in family medicine vs. internal medicine practices in the United States: a cross-sectional study.

BACKGROUND: The benefit of screening for decreasing the risk of death from colorectal cancer (CRC) has been shown, yet many patients in primary care are still not undergoing screening according to guidelines. There are known variations in delivery of preventive health care services among primary care physicians. This study compared self-reported CRC screening rates and patient awareness of the need for CRC screening of patients receiving care from family medicine (FPs) vs. internal medicine (internists) physicians. METHODS: Nationally representative sample of non-institutionalized beneficiaries who received medical care from FPs or internists in 2006 (using Medicare Current Beneficiary Survey). The main outcome was the percentage of patients screened in 2007. We also examined the percentage of patients offered screening. RESULTS: Patients of FPs, compared to those of internists, were less likely to have received an FOBT kit or undergone home FOBT, even after accounting for patients' characteristics. Compared to internists, FPs' patients were more likely to have heard of colonoscopy, but were less likely to receive a screening colonoscopy recommendation (18% vs. 27%), or undergo a colonoscopy (43% vs. 46%, adjusted odds ratios [AOR], 95% confidence interval [CI]-- 0.65, 0.51-0.81) or any CRC screening (52% vs. 60%, AOR, CI--0.80, 0.68-0.94). Among subgroups examined, higher income beneficiaries receiving care from internists had the highest screening rate (68%), while disabled beneficiaries receiving care from FPs had the lowest screening rate (34%). CONCLUSION: Patients cared for by FPs had a lower rate of screening compared to those cared for by internists, despite equal or higher levels of awareness; a difference that remained statistically significant after accounting for socioeconomic status and access to healthcare. Both groups of patients remained below the national goal of 70 percent.

Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Pivotal trials of percutaneous left atrial appendage occlusion (LAAO) used specific postprocedure treatment protocols. OBJECTIVES: This study sought to evaluate patterns of postprocedure care after LAAO with the Watchman device in clinical practice and compare the risk of adverse events for different discharge antithrombotic strategies. METHODS: We evaluated patients in the LAAO Registry of the National Cardiovascular Data Registry who underwent LAAO with the Watchman device between 2016 and 2018. We assessed adherence to the full postprocedure trial protocol including standardized follow-up, imaging, and antithrombotic agents and then evaluated the most commonly used antithrombotic strategies and compared the rates and risk of adverse events at 45 days and 6 months by means of multivariable COX frailty regression. RESULTS: Among 31,994 patients undergoing successful LAAO, only 12.2% received the full postprocedure treatment protocol studied in pivotal trials; the most common protocol deviations were with discharge antithrombotic medications. The most common discharge medication strategies were warfarin and aspirin (36.9%), direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin only (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (5.0%). In multivariable Cox frailty regression, the adjusted risk of any adverse event through the 45-day follow-up visit were significantly lower for discharge on warfarin alone (HR: 0.692; 95% CI: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) compared with warfarin and aspirin. Warfarin alone retained lower risk at the 6-month follow-up. CONCLUSIONS: In contemporary U.S. practice, practitioners rarely used the full U.S. Food and Drug Administration-approved postprocedure treatment protocols studied in pivotal trials of the Watchman device. Discharge after implantation on warfarin or DOAC without concomitant aspirin was associated with lower risk of adverse outcomes.

Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. METHODS: We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. RESULTS: Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of -9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at -12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = -0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = -0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. CONCLUSION: In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Comparison of Mortality and Readmission in Non-Ischemic Versus Ischemic Cardiomyopathy After Implantable Cardioverter-Defibrillator Implantation.

Data is lacking on the contemporary risk of death and readmission following implantable cardioverter-defibrillator (ICD) implantation in patients with non-ischemic cardiomyopathies (NICM) compared with ischemic cardiomyopathies (ICM) in a large nationally representative cohort. We performed a retrospective cohort study using the National Cardiovascular Data Registry ICD Registry linked with Medicare claims from April 1, 2010 to December 31, 2013. We established a cohort of NICM and ICM patients with a left ventricular ejection fraction ≤35% who received a de novo, primary prevention ICD. We compared mortality and readmission using Kaplan-Meier curves and Cox proportional hazard regressions models. We also evaluated temporal trends in mortality. In 31,044 NICM and 68,458 ICM patients with a median follow up of 2.4 years, 1-year mortality was significantly higher in ICM patients (12.3%) compared with NICM (7.9%, p < 0.001). The higher mortality in ICM patients remained significant after adjustment for covariates (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.36 to 1.45), and was consistent in subgroup analyses. These findings were consistent across the duration of the study. ICM patients were also significantly more likely to be readmitted for all causes (adjusted HR 1.15, CI 1.12 to 1.18) and for heart failure (adjusted HR 1.25, CI 1.21 to 1.31). In conclusion, the risks of mortality and hospital readmission after primary prevention ICD implantation were significantly higher in patients with ICM compared with NICM which was consistent across all patient subgroups tested and over the duration of the study.

Survival Following Implantable Cardioverter-Defibrillator Implantation in Patients With Amyloid Cardiomyopathy.

Background Outcomes data in patients with cardiac amyloidosis after implantable cardioverter-defibrillator (ICD) implantation are limited. We compared outcomes of patients with ICDs implanted for cardiac amyloidosis versus nonischemic cardiomyopathies (NICMs) and evaluated factors associated with mortality among patients with cardiac amyloidosis. Methods and Results Using National Cardiovascular Data Registry's ICD Registry data between April 1, 2010 and December 31, 2015, we created a 1:5 propensity-matched cohort of patients implanted with ICDs with cardiac amyloidosis and NICM. We compared mortality between those with cardiac amyloidosis and matched patients with NICM using Kaplan-Meier survival curves and Cox proportional hazards models. We also evaluated risk factors associated with 1-year mortality in patients with cardiac amyloidosis using multivariable Cox proportional hazards regression models. Among 472 patients with cardiac amyloidosis and 2360 patients with propensity-matched NICMs, 1-year mortality was significantly higher in patients with cardiac amyloidosis compared with patients with NICMs (26.9% versus 11.3%, P<0.001). After adjustment for covariates, cardiac amyloidosis was associated with a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.80; 95% CI, 1.56-2.08). In a multivariable analysis of patients with cardiac amyloidosis, several factors were significantly associated with mortality: syncope (HR, 1.78; 95% CI, 1.22-2.59), ventricular tachycardia (HR, 1.65; 95% CI, 1.15-2.38), cerebrovascular disease (HR, 2.03; 95% CI, 1.28-3.23), diabetes mellitus (HR, 1.55; 95% CI, 1.05-2.27), creatinine = 1.6 to 2.5 g/dL (HR, 1.99; 95% CI, 1.32-3.02), and creatinine >2.5 (HR, 4.34; 95% CI, 2.72-6.93). Conclusions Mortality after ICD implantation is significantly higher in patients with cardiac amyloidosis than in patients with propensity-matched NICMs. Factors associated with death among patients with cardiac amyloidosis include prior syncope, ventricular tachycardia, cerebrovascular disease, diabetes mellitus, and impaired renal function.

Outcomes After Implantable Cardioverter-Defibrillator Generator Replacement for Primary Prevention of Sudden Cardiac Death.

BACKGROUND: The effectiveness of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in patients with an ejection fraction (EF) ≤ 35% and clinical heart failure is well established. However, outcomes after replacement of the ICD generator in patients with recovery of EF to >35% and no previous therapies are not well characterized. METHODS AND RESULTS: Between 2001 and 2011, generator replacement was performed at 2 tertiary medical centers in 253 patients (mean age, 68.3 ± 12.7 years; 82% men) who had previously undergone ICD placement for primary prevention but subsequently never received appropriate ICD therapy. EF had recovered to > 35% in 72 of 253 (28%) patients at generator replacement. During median (quartiles) follow-up of 3.3 (1.8-5.3) years after generator replacement, 68 of 253 (27%) experienced appropriate ICD therapy. Patients with EF ≤ 35% were more likely to experience ICD therapy compared with those with EF > 35% (12% versus 5% per year; hazard ratio, 3.57; P = 0.001). On multivariable analysis, low EF predicted appropriate ICD therapy after generator replacement (hazard ratio, 1.96 [1.35-2.87] per 10% decrement; P = 0.001). Death occurred in 25% of patients 5 years after generator replacement. Mortality was similar in patients with EF ≤ 35% and > 35% (7% versus 5% per year; hazard ratio, 1.10; P = 0.68). Atrial fibrillation (3.24 [1.63-6.43]; P < 0.001) and higher blood urea nitrogen (1.28 [1.14-1.45] per increase of 10 mg/dL; P < 0.001) were associated with mortality. CONCLUSIONS: Although approximately one fourth of patients with a primary prevention ICD and no previous therapy have EF >35% at the time of generator replacement, these patients continue to be at significant risk for appropriate ICD therapy (5% per year). These data may inform decisions on ICD replacement.

Computed Tomographic Perfusion Improves Diagnostic Power of Coronary Computed Tomographic Angiography in Women: Analysis of the CORE320 Trial (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) According to Gender.

BACKGROUND: Coronary computed tomographic angiography (CTA) and myocardial perfusion imaging (CTP) is a validated approach for detection and exclusion of flow-limiting coronary artery disease (CAD), but little data are available on gender-specific performance of these modalities. In this study, we aimed to evaluate the diagnostic accuracy of combined coronary CTA and CTP in detecting flow-limiting CAD in women compared with men. METHODS AND RESULTS: Three hundred and eighty-one patients who underwent both CTA-CTP and single-photon emission computed tomography myocardial perfusion imaging preceding invasive coronary angiography as part of the CORE320 multicenter study (Coronary Artery Evaluation Using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) were included in this ancillary study. All 4 image modalities were analyzed in blinded, independent core laboratories. Prevalence of flow-limiting CAD defined by invasive coronary angiography equal to 50% or greater with an associated single-photon emission computed tomography myocardial perfusion imaging defect was 45% (114/252) and 23% (30/129) in males and females, respectively. Patient-based diagnostic accuracy defined by the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone in females was 0.83 (0.75-0.89) and for CTA-CTP was 0.92 (0.86-0.97; P=0.003) compared with men where the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone was 0.82 (0.77-0.87) and for CTA-CTP was 0.84 (0.80-0.89; P=0.29). CONCLUSIONS: The combination of CTA-CTP was performed similarly in men and women for identifying flow-limiting coronary stenosis; however, in women, CTP had incremental value over CTA alone, which was not the case in men. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.

Influence of Gender on the Tolerability, Safety, and Efficacy of Quinidine Used for Treatment of Supraventricular and Ventricular Arrhythmias.

Quinidine, a class IA antiarrhythmic drug (AAD), has been used for the treatment of arrhythmias since the early 1900s. Use has decreased recently because of the availability of newer AADs and concerns about side effects and safety. Quinidine can cause QT prolongation, and women have longer QT intervals and are more susceptible to torsades de pointes (TdP) than are men. We sought to evaluate the influence of gender on quinidine tolerability, safety, and efficacy. We performed retrospective analyses of patients at our institution prescribed quinidine as an AAD between 2000 and 2012. Time to quinidine discontinuation and arrhythmia recurrence were evaluated using Cox proportional hazards models. In 179 patients, 23.5% were women and median age was 65.8 years. Quinidine indication was supraventricular arrhythmias in 68.7% and ventricular arrhythmias in 27.9% of patients. At 3 years after quinidine initiation, Kaplan-Meier probability of quinidine discontinuation was 65.7% for men and 82.4% for women (p = 0.015). Women were more likely than men to discontinue quinidine for QT prolongation (14.3 vs 4.4%, p = 0.036) and TdP (4.8 vs 0%, p = 0.054). After multivariate adjustment, female gender remained independently associated with quinidine discontinuation (adjusted hazard ratio 1.97, p = 0.014). Gender had no influence on arrhythmia recurrence: 1 year after quinidine initiation, Kaplan-Meier probability of freedom from recurrent arrhythmia was 62.4% in men and 57.9% in women (p = 0.33). Quinidine is highly effective in both genders. However, women are more likely than men to experience QT prolongation and TdP on quinidine and are more likely to discontinue quinidine independent of these side effects.