Circulation ( IF 35.5 ) Pub Date : 2022-07-25 , DOI: 10.1161/circulationaha.122.061374
Highlights from the June issues of the subspecialty journals span a variety of topics. The safety of pulsed field ablation, a novel technology for atrial fibrillation, is reported in Circulation: Arrhythmia and Electrophysiology. Associations of truncating variants in the desmosomal gene with arrhythmogenic right ventricular cardiomyopathy from the UK Biobank are analyzed in Circulation: Genomic and Precision Medicine. A randomized trial of assignment to “n-of-1” strategies in statin-hesitant patients is reported in Circulation: Cardiovascular Quality and Outcomes. A large single-center comparison of outcomes of cardiogenic shock from heart failure versus myocardial infarction is presented in Circulation: Heart Failure. The associations of visual coronary and thoracic calcification from nongated chest computed tomography scans with outcomes in patients with very high low-density lipoprotein are reported in Circulation: Cardiovascular Imaging. Last, observational outcomes of long-term dual-antiplatelet therapy are compared with short-term (<12 months) in patients who have undergone left main stenting in Circulation: Cardiovascular Interventions.
Boris Schmidt, MD; Stefano Bordignon, MD; Shota Tohoku, MD; Shaojie Chen, MD; Fabrizio Bologna, MD; Lukas Urbanek, MD; Francesco Pansera, MD; Matthias Ernst, MD; K.R. Julian Chun, MD
Correspondence to: Boris Schmidt, MD, Cardioangiologisches Centrum Bethanien, Wilhelm-Epstein Str 4, 60431 Frankfurt/Main, Germany. Email b.
Background: Pulsed field ablation represents an energy source specific for ablation of cardiac arrhythmias including atrial fibrillation. The aim of the study was to describe the adoption and the process of streamlining procedures with a new ablation technology.
Methods: All-comer atrial fibrillation patients (n=191; mean age 69±12 years) underwent catheter ablation with a pulsed field ablation device exclusively using analog-sedation. In the validation phase (n=25), device electrogram quality was compared with a circular mapping catheter to assess pulmonary vein isolation and esophageal temperature monitoring was used. In the streamline phase (n=166), a single-catheter approach was implemented. Postprocedural cerebral magnetic resonance imaging was performed in 53 patients. In 52 patients, esophageal endoscopy was performed at day 1 after the procedure. Follow-up was performed using 72 hours Holter ECGs.
Results: On a pulmonary vein basis, pulmonary vein isolation rate was 100% including a single shot isolation rate of 99.5%. The electrogram information of the pulsed field ablation catheter and the circular mapping catheter were 100% congruent. Neither esophageal temperature rises nor esophageal thermal injury were observed. Two minor strokes occurred, presumable due to air embolism during catheter exchanges through the large bore sheath (13.8 F ID). In the streamline phase, reduced procedure times (46±14 versus 38±13 minutes, P=0.004), no further strokes and a low incidence of silent cerebral injury (10/53 patients; 19%) were noted. During short-term follow-up, 17/191 patients (9%) had a atrial tachyarrhythmia recurrence.
Conclusions: The pulsed field ablation device allows for simple and safe simple single shot pulmonary vein isolation using standard sedation protocols. Procedural speed and efficacy are remarkable and streamlining measures have added safety.
Circ Arrhythm Electrophysiol. 2022;15:e010817. doi: 10.1161/CIRCEP.121.010817. Epub May 26, 2022.
Robyn J. Hylind, MS, CGC; Alexandre C. Pereira, MD, PhD; Daniel Quiat, MD, PhD; Stephanie F. Chandler, MD; Thomas M. Roston, MD, PhD; William T. Pu, MD; Vassilios J. Bezzerides, MD, PhD; Jonathan G. Seidman, PhD; Christine E. Seidman, MD; Dominic J. Abrams, MD, MRCP, MBA
Correspondence to: Robyn J. Hylind, MS, CGC, or Dominic J. Abrams, MD, MRCP, MBA, Department of Cardiology, Boston Children’s Hospital, Boston, MA 02115. Email robyn.
Background: Truncating variants in the desmosomal gene PKP2 (PKP2tv) cause arrhythmogenic right ventricular cardiomyopathy (ARVC) yet display varied penetrance and expressivity.
Methods: We identified individuals with PKP2tv from the UK Biobank (UKB) and determined the prevalence of an ARVC phenotype and other cardiovascular traits based on clinical and procedural data. The PKP2tv minor allelic frequency in the UKB was compared with a second cohort of probands with a clinical diagnosis of ARVC (ARVC cohort), with a figure of 1:5000 assumed for disease prevalence. In silico predictors of variant pathogenicity (combined annotation-dependent depletion and Splice AI) were assessed.
Results: PKP2tv were identified in 193/200 643 (0.10%) UKB participants, with 47 unique PKP2tv. Features consistent with ARVC were present in 3 (1.6%), leaving 190 with PKP2tv without manifest disease (UKB cohort; minor allelic frequency 4.73×10−4). The ARVC cohort included 487 ARVC probands with 144 distinct PKP2tv, with 25 PKP2tv common to both cohorts. The odds ratio for ARVC for the 25 common PKP2tv was 0.047 (95% CI, 0.001–0.268; P=2.43×10−6), and only favored ARVC (odds ratio >1) for a single variant, p.Arg79*. In silico variant analysis did not differentiate PKP2tv between the 2 cohorts. Atrial fibrillation was over-represented in the UKB cohort in those with PKP2tv (7.9% versus 4.3%; odds ratio, 2.11; P=0.005).
Conclusions: PKP2tv are prevalent in the population and associated with ARVC in only a small minority, necessitating a more detailed understanding of how PKP2tv cause ARVC in combination with associated genetic and environmental risk factors.
Circ Genom Precis Med. 2022;15:e003507. doi: 10.1161/CIRCGEN.121.003507. Epub May 10, 2022.
Kate Tudor, PhD; Jenny Brooks, MSc; Jeremy Howick, PhD; Robin Fox, FRCGP; Paul Aveyard, PhD
Correspondence to: Kate Tudor, PhD, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK, OX3 7JX; or Paul Aveyard, PhD, Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK, OX2 6GG. Email kate.
Background: The aim was to assess whether an intervention incorporating a practicable open-label n-of-1 trial would lead to greater uptake of statin than usual care and comparable uptake to a closed-label gold-standard n-of-1 trial.
Methods: We enrolled patients who had stopped or declined statins into a 3-arm trial (usual care, unblinded, and blinded n-of-1 intervention arms). Physicians advised participants randomized to usual care to take statin therapy to prevent cardiovascular disease. In both intervention arms, physicians delivered a theoretically informed intervention endorsing the value of experimenting with medication in n-of-1 trials to assess whether it caused side-effects. In these trials, participants alternated between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and recorded symptoms and symptom attributions for 6 months. Thereafter, physicians discussed participants’ symptom reports during active/inactive treatment periods and asked participants to resume statins if appropriate.
Results: Seventy-three were randomized to the intervention arms and 20 to the control group. Fifty-six of 73 (77%) attempted the n-of-1 experiment; 28/36 (78%) in the unblinded arm; and 28/37 (76%) in the blinded arm. Forty-three of 56 (77%) completed the 6-month experiment and received feedback from the physician; 20/28 (71%) in the unblinded arm and 23/28 (82%) in the blinded arm. Thirty-three of 76 (45%) people restarted statins in the n-of-1 arms compared with 4/20 (20%) in the control arm, difference 24% (95% CI, 5%–43%; P=0.041). There was no evidence this differed between blinded and unblinded arms, difference 2% (95% CI, −20% to 24%; P=0.86). Adverse events occurred at a similar rate on and off statin.
Conclusions: In patients refusing or intolerant of statin, supporting experimentation with n-of-1 trials increases medication uptake compared with usual care. Alternating on-off medication in unblinded n-of-1 experiments appears as effective as a blinded experiment.
Circ Cardiovasc Qual Outcomes. 2022;15:e007793. doi: 10.1161/CIRCOUTCOMES.120.007793. Epub June 14, 2022.
Shashank S. Sinha, MD, MSc; Carolyn M. Rosner, MSN, NP-C, MBA; Behnam N. Tehrani, MD; Aneel Maini, BS; Alexander G. Truesdell, MD; Seiyon Ben Lee, PhD; Pramita Bagchi, PhD; James Cameron, MS; Abdulla A. Damluji, MD, PhD, MPH; Mehul Desai, MD; Shashank S. Desai, MD, MBA; Kelly C. Epps, MD; Christopher deFilippi, MD; M. Casey Flanagan, MD; Leonard Genovese, MD; Hala Moukhachen, MD; James J. Park, BA; Mitchell A. Psotka, MD, PhD; Anika Raja, BS, MPH; Palak Shah, MD, MS; Matthew W. Sherwood, MD, MHS; Ramesh Singh, MD; Daniel Tang, MD; Karl D. Young, PA; Timothy Welch, MD; Christopher M. O’Connor, MD; Wayne B. Batchelor, MD, MHS
Correspondence to: Wayne Batchelor, MD, MHS, Inova Heart and Vascular Institute, 3300 Gallows Rd, Ste I-4109, Falls Church, VA 22042. Email wayne.
Background: Little is known about clinical characteristics, hospital course, and longitudinal outcomes of patients with cardiogenic shock (CS) related to heart failure (HF-CS) compared to acute myocardial infarction (AMI; CS related to AMI [AMI-CS]).
Methods: We examined in-hospital and 1-year outcomes of 520 (219 AMI-CS, 301 HF-CS) consecutive patients with CS (January 3, 2017–December 31, 2019) in a single-center registry.
Results: Mean age was 61.5±13.5 years, 71% were male, 22% were Black patients, and 63% had chronic kidney disease. The HF-CS cohort was younger (58.5 versus 65.6 years, P<0.001), had fewer cardiac arrests (15.9% versus 35.2%, P<0.001), less vasopressor utilization (61.8% versus 82.2%, P<0.001), higher pulmonary artery pulsatility index (2.14 versus 1.51, P<0.01), lower cardiac power output (0.64 versus 0.77 W, P<0.01) and higher pulmonary capillary wedge pressure (25.4 versus 22.2 mm Hg, P<0.001) than patients with AMI-CS. Patients with HF-CS received less temporary mechanical circulatory support (34.9% versus 76.3% P<0.001) and experienced lower rates of major bleeding (17.3% versus 26.0%, P=0.02) and in-hospital mortality (23.9% versus 39.3%, P<0.001). Postdischarge, 133 AMI-CS and 229 patients with HF-CS experienced similar rates of 30-day readmission (19.5% versus 24.5%, P=0.30) and major adverse cardiac and cerebrovascular events (23.3% versus 28.8%, P=0.45). Patients with HF-CS had lower 1-year mortality (n=123, 42.6%) compared to the patients with AMI-CS (n=110, 52.9%, P=0.03). Cumulative 1-year mortality was also lower in patients with HF-CS (log-rank test, P=0.04).
Conclusions: Patients with HF-CS were younger, and despite lower cardiac power output and higher pulmonary capillary wedge pressure, less likely to receive vasopressors or temporary mechanical circulatory support. Although patients with HF-CS had lower in-hospital and 1-year mortality, both cohorts experienced similarly high rates of postdischarge major adverse cardiovascular and cerebrovascular events and 30-day readmission, highlighting that both cohorts warrant careful long-term follow-up.
Circ Heart Fail. 2022;15:e009279. doi: 10.1161/CIRCHEARTFAILURE.121.009279. Epub May 5, 2022.
Francesco Castagna, MD; Jeremy Miles, MD; Javier Arce, MD; Ephraim Leiderman, MD; Patrick Neshiwat, MD; Paul Ippolito, MD; Patricia Friedmann, MS; Aldo Schenone, MD; Lili Zhang, MD, ScM; Carlos J. Rodriguez, MD, MPH; Michael J. Blaha, MD, MPH; Jeffrey M. Levsky, MD, PhD; Mario J Garcia, MD; Leandro Slipczuk, MD, PhD
Correspondence to: Leandro Slipczuk, MD, PhD, Montefiore Medical Center, Cardiology Division. 111 E 210th, Bronx, NY 10467. Email [email protected]
Background: Current guidelines recommend coronary artery calcium (CAC) scoring for stratification of atherosclerotic cardiovascular disease risk only in patients with borderline to intermediate risk score by the pooled cohort equation with low-density lipoprotein-cholesterol (LDL-C) of 70 to 190 mg/dL. It remains unknown if CAC or thoracic aorta calcification (TAC), detected on routine chest computed tomography, can provide further risk stratification in patients with LDL-C≥190 mg/dL.
Methods: From a multisite medical center, we retrospectively identified all patients from March 2005 to June 2021 age ≥40 years, without established atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL who had non-gated non-contrast chest computed tomography within 3 years of LDL-C measurement. Ordinal CAC and TAC scores were measured by visual inspection. Kaplan-Meier curves and multivariable Cox-regression models were built to ascertain the association of CAC and TAC scores with all-cause mortality.
Results: We included 811 patients with median age 59 (53–68) years, 262 (32.3%) were male, and LDL-C median level was 203 (194–217) mg/dL. Patients were followed for 6.2 (3.29–9.81) years, and 109 (13.4%) died. Overall, 376 (46.4%) of patients had CAC=0 and 226 (27.9%) had TAC=0. All-cause mortality increased with any CAC and moderate to severe TAC. In a multivariate model, patients with CAC had a significantly higher mortality compared with those without CAC: mild hazard ratio (HR), 1.71 (1.03–2.83), moderate HR, 2.12 (1.14–3.94), and severe HR, 3.49 (1.94–6.27). Patients with moderate TAC (HR, 2.34 [1.19–4.59]) and those with severe TAC (HR, 3.02 [1.36–6.74]) had higher mortality than those without TAC.
Conclusions: In patients without history of atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL, the presence and severity of CAC and TAC are independently associated with all-cause mortality.
Circ Cardiovasc Imaging. 2022;15:e014135. DOI: 10.1161/CIRCIMAGING.122.014135. Epub June 21, 2022.
Hao-Yu Wang, MD; Ke-Fei Dou, MD; Changdong Guan, MSc; Lihua Xie, MSc; Yunfei Huang, PhD; Rui Zhang, MD; Weixian Yang, MD; Yongjian Wu, MD; Yuejin Yang, MD; Shubin Qiao, MD; Runlin Gao, MD; Bo Xu, MBBS
Correspondence to: Ke-Fei Dou, MD, Cardiometabolic Medicine Center, Coronary Heart Disease Center, Department of Cardiology, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Cardiovascular Diseases, A 167, Beilishi Rd, Xicheng District, Beijing, 100037, China; or Bo Xu, MBBS, Catheterization Laboratories, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Cardiovascular Diseases, A 167, Beilishi Rd, Xicheng District, Beijing, 100037. Email [email protected]
Background: The appropriate duration of dual antiplatelet therapy (DAPT) and risk-benefit ratio for long-term DAPT in patients with left main (LM) disease undergoing percutaneous coronary intervention remains uncertain.
Methods: Four thousand five hundred sixty-one consecutive patients with stenting of LM disease at a single center from January 2004 to December 2016 were enrolled. Decision to discontinue or remain on DAPT after 12 months was left to an individualized decision-making based on treating physicians by weighing the patient’s risks of ischemia versus bleeding and considering patient preference. The primary outcome was a composite of death, myocardial infarction, stent thrombosis, or stroke at 3 years. Key safety outcome was 3-year rate of Bleeding Academic Research Consortium 2, 3, or 5 bleeding.
Results: Of 3865 patients free of ischemic and bleeding events at 12 months, 1727 (44.7%) remained on DAPT (mostly clopidogrel based [97.7%]) beyond 12 months after LM percutaneous coronary intervention. DAPT>12-month versus ≤12-month DAPT was associated with a significant reduced risk of 3-year primary outcome (2.6% versus 4.6%; adjusted hazard ratio: 0.59 [95% CI, 0.41–0.84]). The same trend was found for other ischemic end points: death (0.9% versus 3.0%; Plog-rank<0.001), cardiovascular death (0.5% versus 1.7%; Plog-rank=0.001), myocardial infarction (0.8% versus 1.9%; Plog-rank=0.005), and stent thrombosis (0.4% versus 1.1%; Plog-rank=0.017). The key safety end point was not significantly different between 2 regimens (1.8% versus 1.6%; adjusted hazard ratio: 1.07 [95% CI, 0.65–1.74]). The effect of DAPT>12 month on primary and key safety outcomes was consistent across clinical presentations, high bleeding risk, P2Y12 inhibitor, and LM bifurcation percutaneous coronary intervention approach.
Conclusions: In a large cohort of patients free from clinical events during the first year after LM percutaneous coronary intervention and at low apparent future bleeding risk, an individualized patient-tailored approach to longer duration (>12 month) of DAPT with aspirin plus a P2Y12 inhibitor (mostly clopidogrel) improved both composite and individual efficacy outcomes by reducing ischemic risk, without a concomitant increase in clinically relevant bleeding.
Circ Cardiovasc Interv. 2022;15:e011536. doi: 10.1161/CIRCINTERVENTIONS.121.011536. Epub May 18, 2022.
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