Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. METHODS: We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus <90%. RESULTS: We included 75 patients (age 74 ± 11 years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and <90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90% versus <90% (15.7 ± 9.3% vs. 7.5 ± 9.6%, p = .003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p = .005 and .02, respectively). CONCLUSION: A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.

Impact of Biopsy Proven Liver Fibrosis on Patients Undergoing Evaluation and Treatment for Advanced Heart Failure Surgical Therapies.

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p = 0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p = 0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p = 0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings.

UltraSound Axillary Vein Access (USAA): Learning curve and randomized comparison to traditional venous access for cardiac device implantation.

BACKGROUND: Many techniques exist for venous access (VA) during cardiac implantable electronic device (CIED) implantation. OBJECTIVE: We sought to evaluate the learning curve with ultrasound (US) guided axillary vein access (USAA). METHODS: Single-center prospective randomized controlled trial of patients undergoing CIED implantation. Patients were randomized in a 2:1 fashion to USAA versus conventional VA techniques. The primary outcomes were the success rates, VA times and 30-day complication rates. RESULTS: The study included 100 patients (age 68 ± 14 years, BMI 27 ± 4 kg/m2 ). USAA was successful in 66/70 implants (94%). Initial attempts at conventional VA included 47% axillary (n = 14), 30% (n = 9) cephalic, and 23% (n = 7) subclavian. The median access time was longer for USAA than conventional access (8.3 IQR 4.2-15.3 min vs. 5.2 IQR 3.4-8.6 min, p = .009). Among the five inexperienced USAA implanters, there was a significant improvement in median access time from first to last tertile of USAA implants (17.0 IQR 7.0-21.0 min to 8.6 IQR 4.5-10.8 min, p = .038). The experienced USAA implanter had similar access times with USAA compared with conventional access (4.0 IQR 3.3-4.7 min vs. 5.2 IQR 3.4-8.6 min, p = .15). Venograms were less common with USAA than conventional access (2% vs. 33%, p < .0001). The 30-day complication rate was similar with USAA (n = 4/70, 6%) versus conventional (n = 3/30, 10%, p = .44). CONCLUSION: Although the success rate with USAA was high, there was a significant learning curve. Once experienced with the USAA technique, there is the potential for reduced complications without adding to the procedure duration.

Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock: Lifeline of Modern Day CICU.

Cardiogenic shock (CS) portends an extremely high mortality of nearly 50% during index hospitalization. Prompt diagnoses of CS, its underlying etiology, and efficient implementation of treatment modalities, including mechanical circulatory support (MCS), are critical especially in light of such high predicted mortality. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides the most comprehensive cardiopulmonary support in critically ill patients and hence has seen a steady increase in its utilization over the past decade. Hence, a good understanding of VA-ECMO, its role in treatment of CS, especially when compared with other temporary MCS devices, and its complications are vital for any critical care cardiologist. Our review of VA-ECMO aims to provide the same.

Ultrasound guided axillary vein access: An alternative approach to venous access for cardiac device implantation.

INTRODUCTION: Ultrasound guided axillary vein access (UGAVA) is an emerging approach for cardiac implantable electronic device (CIED) implantation not widely utilized. METHODS AND RESULTS: This is a retrospective, age and sex-matched cohort study of CIED implantation from January 2017 to July 2019 comparing UGAVA before incision to venous access obtained after incision without ultrasound (conventional). The study population included 561 patients (187 with attempted UGAVA, 68 ± 13 years old, 43% women, body mass index (BMI) 30 ± 8 kg/m2 , 15% right-sided, 43% implantable cardioverter-defibrillator, 15% upgrades). UGAVA was successful in 178/187 patients (95%). In nine patients where UGAVA was abandoned, the vein was too deep for access before incision. BMI was higher in abandoned patients than successful UGAVA (38 ± 6 vs. 28 ± 6 kg/m2 , p < .0001). Median time from local anesthetic to completion of UGAVA was 7 min (interquartile range [IQR]: 4-10) and median procedure time 61 min (IQR: 50-92). UGAVA changed implant laterality in two patients (avoiding an extra incision in both) and could have prevented unnecessary incision in four conventional patients. Excluding device upgrades, there was reduced fluoroscopy time in UGAVA versus conventional (4 vs. 6 min; IQR: 2-5 vs. 4-9; p < .001). Thirty-day complications were similar in UGAVA versus conventional (n = 7 vs. 26, 4 vs. 7%; p = .13, p = .41 adjusting for upgrades), partly driven by a trend towards reduced pneumothorax (n = 0 vs. 3, 0 vs. 1%; p = .22). CONCLUSIONS: UGAVA is a safe approach for CIED implantation and helps prevent an extra incision if a barrier is identified changing laterality preincision.

In-Hospital Outcomes and Trends of Tricuspid Valve Surgery in Heart Transplant Patients.

INTRODUCTION: Tricuspid valve (TV) regurgitation is the most common valvular pathology after orthotopic heart transplant (OHT). The number of transplants being performed is increasing with patients living longer after heart transplant. Data on TV surgery in OHT recipients is limited. METHODS: We sought to analyze the outcomes of patients undergoing TV surgery from a large diverse, multicentric, nationwide cohort using the Nationwide Inpatient Sample (NIS) database. RESULTS: A total of 42,766 TV repair or replacement (bioprosthetic and mechanical) involving adult patients (age ≥18 years) between 2007 and September 2015 were identified. Of these, 366 were performed in patients with OHT. TV repair was the most common surgery performed in both groups (OHT group and native heart group). Compared to the native group, patients with OHT had a significantly higher incidence of cardiogenic shock (20 vs. 11%, p = 0.024), acute kidney injury (AKI) (59 vs. 30%, p < 0.001), and AKI requiring hemodialysis (13 vs. 4%, p < 0.001). Also, the mean length of stay for the index admission was significantly longer in the OHT group (27 vs. 17 days, p = 0.008). The mortality rate was similar between the two groups (7 vs. 8%, p = 0.753). The number of TV surgeries performed in OHT patients from 2007 to 2014 have remained stable (p = 0.803) compared to those in native heart patients which showed a significantly increasing trend (p = 0.019) during the same time period. CONCLUSIONS: TV surgery remains an important treatment modality among the OHT population and carries a similar mortality during index hospitalization as that in native heart patients undergoing TV surgery.

Seeking shelter from the storm: Conservation and management of imperiled species in a changing climate.

Climate change is anticipated to exacerbate the extinction risk of species whose persistence is already compromised by habitat loss, invasive species, disease, or other stressors. In coastal areas of the southeastern United States (USA), many imperiled vertebrates are vulnerable to hurricanes, which climate models predict to become more severe in the 21st century. Despite this escalating threat, explicit adaptation strategies that address hurricane threats, in particular, and climate change more generally, are largely underrepresented in recovery planning and implementation. We provide a basis for stronger emphasis on strategic planning for imperiled species facing the increasing threat of catastrophic hurricanes. Our reasoning comes from observations of short-term environmental and biological impacts of Hurricane Michael, which impacted the Gulf Coast of the southeastern USA in October 2018. During this storm, St. Marks National Wildlife Refuge, located along the northern Gulf of Mexico's coast in the panhandle region of Florida, received storm surge that was 3.0-3.6 m (NAVD88) above sea level. Storm surge pushed sea water into some ephemeral freshwater ponds used for breeding by the federally threatened frosted flatwoods salamander (Ambystoma cingulatum). After the storm, specific conductance across all ponds measured varied from 80 to 23,100 µS/cm, compared to 75 to 445 µS/cm in spring 2018. For 17 overwashed wetlands that were measured in both spring and fall 2018, posthurricane conductance observations were, on average, more than 90 times higher than in the previous spring, setting the stage for varying population responses across this coastal landscape. Importantly, we found live individual flatwoods salamanders at both overwashed and non-overwashed sites, although we cannot yet assess the demographic consequences of this storm. We outline actions that could be incorporated into climate adaptation strategies and recovery planning for imperiled species, like A. cingulatum, that are associated with freshwater coastal wetlands in hurricane-prone regions.

Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase.

The N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells. Altered polyamine levels are associated with a variety of cancers as well as other diseases, and key enzymes in the polyamine pathway, including SSAT, are being explored as potential therapeutic drug targets. We have expressed and purified human SSAT in Escherichia coli and characterized its kinetic and chemical mechanism. Initial velocity and inhibition studies support a random sequential mechanism for the enzyme. The bisubstrate analogue, N1-spermine-acetyl-coenzyme A, exhibited linear, competitive inhibition against both substrates with a true Ki of 6 nM. The pH-activity profile was bell-shaped, depending on the ionization state of two groups exhibiting apparent pKa values of 7.27 and 8.87. The three-dimensional crystal structure of SSAT with bound bisubstrate inhibitor was determined at 2.3 A resolution. The structure of the SSAT-spermine-acetyl-coenzyme A complex suggested that Tyr140 acts as general acid and Glu92, through one or more water molecules, acts as the general base during catalysis. On the basis of kinetic properties, pH dependence, and structural information, we propose an acid/base-assisted reaction catalyzed by SSAT, involving a ternary complex.