Journal Scan

Hypertension

Article 1: Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy

J Am Coll Cardiol. 2022, June 21;79(24):2401-2411.

Lisa D Levine, Bonnie Ky, Julio A Chirinos, Jessica Koshinksi, Zoltan Arany, Valerie Riis, Michal A Elovitz, Nathanael Koelper, and Jennifer Lewey.

Abstract

Background: Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of cardiovascular disease (CVD) 20 to 30 years later; however, cardiovascular (CV) risk in the decade after HDP is less studied.

Objectives: The purpose of this study was to evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier.

Methods: This is a prospective study of patients with and without a diagnosis of HDP ≥10 years earlier (2005-2007) who underwent in-person visits with echocardiography, arterial tonometry, and flow-mediated dilation of the brachial artery.

Results: A total of 135 patients completed assessments (84 with and 51 without a history of HDP); 85% self-identified as Black. Patients with a history of HDP had a 2.4-fold increased risk of new hypertension compared with those without HDP (56.0% vs 23.5%; adjusted relative risk: 2.4; 95% confidence interval: 1.39-4.14) with no differences in measures of left ventricular structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function. Patients who developed hypertension, regardless of HDP history, had greater left ventricular remodeling, including greater relative wall thickness; worse diastolic function, including lower septal and lateral e’ and E/A ratio; more abnormal longitudinal strain; and higher effective arterial elastance than patients without hypertension.

Conclusions: We found a 2.4-fold increased risk of hypertension 10 years after HDP. Differences in noninvasive measures of CV risk were driven mostly by the hypertension diagnosis, regardless of HDP history, suggesting that the known long-term risk of CVD after HDP may primarily be a consequence of hypertension development.

Comments: This prospective study highlighted the importance of early detection of hypertension in patients at high risk. Contrary to the belief, the patients developed hypertension within a decade of hypertensive disorders of pregnancy (HDP). Around 60% of all patients meeting the criteria for either stage 1 or 2 hypertension didn’t have a formal diagnosis. The history of HDP may be primarily responsible for the long-term risk of CVD as evident by the presence of echocardiographic markers of CV risk in those who developed chronic hypertension than those without a history of HDP. This trial paves the way for future efforts to improve postpartum CV care, enabling us to grasp the opportunity to reduce maternal and pregnancy-related morbidity and mortality.

Article 2: Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition

Circulation. 2022;11(7):146.

Yuliya Lytvyn, Karen Kimura, Nuala Peter, Vesta Lai, Josephine Tse, Leslie Cham, Bruce A Perkins, Nima Suleymanov, and David ZI Cherney.

Abstract

Background: The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration.

Methods: Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial. Recruitment was stopped early because of an unexpectedly low proportion of patients with hyperfiltration. Measurements were obtained after each of the 6 treatment phases over 19 weeks: (a) baseline without treatment, (b) 4-week run-in with ramipril treatment alone, (c) 4-week combined empagliflozin-ramipril treatment, (d) a 4-week washout, (e) 4-week combined placebo-ramipril treatment, and (f) 1-week follow-up. The primary endpoint was glomerular filtration rate (GFR) after combination treatment with empagliflozin-ramipril compared with placebo-ramipril. GFR was corrected for ramipril treatment alone before randomization. At the end of the study phase, the following outcomes were measured under clamped euglycemia (4-6 mmol/L): inulin (GFR) and para-amino hippurate (effective renal plasma flow) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, noninvasive cardiac output monitoring, plasma and urine biochemistry, markers of the renin-angiotensin-aldosterone system, and oxidative stress.

Results: Combination treatment with empagliflozin-ramipril resulted in an 8 mL/min/1.73 m² lower GFR compared with placebo-ramipril treatment (P = .0061) without significant changes to effective renal plasma flow. GFR decrease was accompanied by a 21.3 mL/min lower absolute proximal fluid reabsorption rate (P = .0092), a 3.1 mmoL/min lower absolute proximal sodium reabsorption rate (P = .0056), and a 194 ng/mmoL creatinine lower urinary 8-isoprostane level (P = .0084) relative to placebo-ramipril combination treatment. Sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor combination treatment resulted in additive blood pressure-lowering effects (clinic systolic blood pressure lowered by 4 mm Hg [P = .0112]; diastolic blood pressure lowered by 3 mm Hg [P = .0032]) in conjunction with 94.5 dynes × sex/cm⁵ lower total peripheral resistance (P = .0368). There were no significant changes observed in ambulatory blood pressure, arterial stiffness, heart rate variability, or cardiac output with the addition of empagliflozin.

Conclusions: Adding sodium-glucose cotransporter 2 inhibitor treatment to angiotensin-converting enzyme inhibitor resulted in an expected GFR dip, suppression of oxidative stress markers, additive declines in blood pressure, and declines in total peripheral resistance. These changes are consistent with a protective physiologic profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding sodium-glucose cotransporter 2 inhibitors to conservative therapy.

Comments: Dual inhibition pathway was proved to be beneficial in patients with the acute coronary syndrome. In the same line, this novel study has proven that adding ACE inhibition to the SGLT2 inhibitors was proven to be renoprotective, improving the eGFR without affecting the arterial stiffness, heart rate variability, and cardiac output in patients with normofiltration.

Cardiomyopathy

Article 3: Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy

J Am Coll Cardiol. 2022;79(16):1565-1575.

Anne M Dybro, Torsten B Rasmussen, Roni R Nielsen, Bertil T Ladefoged, Mads J Andersen, Morten K Jensen, and Steen H Poulsen.

Abstract

Background: The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.

Objectives: This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.

Methods: This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (∇PCWP) between peak exercise and rest.

Results: No treatment effect on DPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = .12). At rest, metoprolol lowered heart rate (P < .0001), left ventricular outflow tract (LVOT) gradient (P = .01), and increased left ventricular end-diastolic volume (P = .02) and stroke volume (SV) (+6.4; 95% confidence interval [CI]: 0.02-17.7; P = .049). During peak exercise, metoprolol was associated with a lower heart rate (P < .0001), a lower LVOT gradient (P = .0005), lesser degree of mitral regurgitation (P = .004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = .008).

Conclusions: In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

Comments: This study is quite interesting regarding the effect of beta-blockers that they did not reduce PCWP despite increasing the stroke volume (SV) at rest and during exercise. The lack of effect can be due to the negative effect of beta-blockers on lusitropy thereby not improving PCWP. Severe diastolic dysfunction due to abnormalities in the myocyte, extracellular matrix, and pericardial restraint might not improve with short-term betablockade. More surprising is that the severity of mitral regurgitation was reduced, but there was no effect of metoprolol on the amplitude of the PAWP V wave pressure. Before concluding no benefit, the crossover design with potential of a carryover and period effect, reduction of PCWP at mid A wave and PADP producing a type II error, measurement of SV by thermodilution and 3D Echo, exercise being done in semi-supine position limitations should be noted. However, they are still the drug of choice in hypertrophic cardiomyopathy and are the only one that increases stroke volume.

Valvular Heart Disease

Article 4: Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: The AVATAR Trial

Circulation. 2022;145:648-658.

Marko Banovic, Svetozar Putnik, Martin Penicka, Gheorghe Doros, Marek A Deja, Radka Kockova, Martin Kotrc, Sigita Glaveckaite, Hrvoje Gasparovic, Nikola Pavlovic, Lazar Velicki, Stefano Salizzoni, Wojtek Wojakowski, Guy Van Camp, Serge D Nikolic, Jozef Bartunek, and on behalf of the AVATAR Trial Investigators.

Abstract

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated.

Methods: The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm² with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mmHg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries.

Results: Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n = 78) or conservative treatment (n = 79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with an operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite endpoint than those in the conservative arm (hazard ratio, 0.46 [95% confidence interval, 0.23-0.90]; P = .02). There was no statistical difference in secondary endpoints, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome.

Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms.

Comments: The management of aortic stenosis is expanding its horizon over the last 2 decades. The decision to operate on asymptomatic patients with severe AS and normal left ventricular (LV) function remains a matter of debate. A watchful strategy to delay surgery in this subset has been favored traditionally as the risk of sudden cardiac death in such patients has been reported to be low. However, the risk of sudden cardiac death is higher than in the general population. Sustained pressure overload due to AS is associated with structural and functional impairment of LV leading to adverse effects. When patients with asymptomatic AS with normal left ventricular ejection fraction have been followed for a year, the mortality at end of 1 year was 10%, with increased MACE occurring at 6 months. This trial defers from the randomized RECOVERY trial in that the patients included here were having severe AS, degenerative pathology, normal LV function, a negative exercise test, and a multinational study close to real-world practice (in RECOVERY—the patients enrolled were of critical AS (>4.5 m/s), bicuspid aortic valve, no requirement of exercise testing, single country clinical practice). This trial re-emphasizes the role of early surgery rather than watchful waiting in patients with severe AS and has a mortality benefit.

Article 5: Thrombolysis or Surgery in Patients With Obstructive Mechanical Valve Thrombosis: The Multicenter HATTUSHA Study

J Am Coll Cardiol. 2022 Mar;79(10):977-989.

Mehmet Özkan, Sabahattin Gündüz, Ahmet Güner, Macit Kalçık, Mustafa Ozan Gürsoy, Begüm Uygur, Nurşen Keleş, Hasan Kaya, Alev Kılıçgedik, Emrah Bayam, Semih Kalkan, Mehmet Ali Astarcıoğlu, Süleyman Karakoyun, Mahmut Yesin, Duygu İnan, Ali Fedakar, Sabit Sarıkaya, Mehmet Aksüt, Burak Onan, and Cevdet Uğur Koçoğulları.

Abstract

Background: Prosthetic valve thrombosis (PVT) is one of the life-threatening complications of prosthetic heart valve replacement. Due to the lack of randomized controlled trials, the optimal treatment of PVT remains controversial between thrombolytic therapy (TT) and surgery.

Objectives: This study aimed to prospectively evaluate the outcomes of TT and surgery as the first-line treatment strategy in patients with obstructive PVT.

Methods: A total of 158 obstructive PVT patients (women: 103 [65.2%]; median age 49 years [interquartile range {IQR}: 39-60 years]) were enrolled in this multicenter observational prospective study. TT was performed using slow (6 h) and/or ultraslow (25 h) infusion of low-dose tissue plasminogen activator (t-PA) (25 mg) mostly in repeated sessions. The primary endpoint of the study was 3-month mortality following TT or surgery.

Results: The initial management strategy was TT in 83 (52.5%) patients and surgery in 75 (47.5%) cases. The success rate of TT was 90.4% with a median t-PA dose of 59 mg (IQR: 37.5-100 mg). The incidences of outcomes in surgery and TT groups were as follows: minor complications (29 [38.7%] and 7 [8.4%], respectively), major complications (31 [41.3%] and 5 [6%], respectively), and the 3-month mortality rate (14 [18.7%] and 2 [2.4%], respectively).

Conclusions: Low-dose and slow/ultraslow infusion of t-PA were associated with low complications and mortality and high success rates and should be considered a viable treatment in patients with obstructive PVT.

Comments: Prosthetic valve thrombosis is the most common complication which is life-threatening in a patient with prosthetic heart valve replacement. Surgery is the preferred treatment in patients with left side thrombosis and a size of more than 10 mm². However, surgery has a high mortality rate, risk of periprocedural complications, and bleeding risk. The mortality rates of surgery for thrombectomy and valve replacement were 15.4% and 19.4% in this study. Rethrombosis requiring management during the 3-month follow-up period was almost twice in the surgery group compared to the thrombolytic therapy group (6.7% vs 2.5%). The use of low dose (25 mg) and slow (6 h)/ultraslow (25 h) infusion of thrombolytic therapy was found to be beneficial with fewer complications when compared to surgery. These regimens were found to have reduced the risk of hemorrhage and thromboembolism when compared with higher doses or faster infusions of tPA or streptokinase. The major guidelines regarding the management of PVT remain controversial (The ACC/AHA—recommends initial treatment with slow infusion, low dose TT, or emergency surgery for symptomatic left-sided PVT whereas ESC/EACTS still give priority to surgery in the management of PVT). To change the existing guidelines, a larger randomized trial is warranted to validate the findings of this study.

Heart Failure

Article 6: Impact of Intravenous Ferric Carboxymaltose on Heart Failure With Preserved and Reduced Ejection Fraction

ESC Heart Failure. 2022;9:133-145.

Raquel López-Vilella, Silvia Lozano-Edo, Patricia Arenas Martín, Pablo Jover-Pastor, Meryem Ezzitouny, José Sorolla Romero, María Calvo Asensio, Julia Martínez-Solé, Borja Guerrero Cervera, José Carlos Sánchez Martínez, Víctor Donoso Trenado, Ignacio Sánchez-Lázaro, Luis Martinez Dolz, and Luis Almenar Bonet.

Abstract

Aims: Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyze the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF).

Methods and Results: We conducted a retrospective, single-center study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID (defined as ferritin <100 µg/L or ferritin 100-300 µg/L with transferrin saturation [TSAT] <20%). Clinical, laboratory, and echocardiographic parameters were analyzed before and after administration. After FCM administration, overall ferritin, TSAT, and hemoglobin levels increased up to 5-fold, 1.6-fold, and 1.1-fold, respectively, relative to baseline values in HF patients with reduced and preserved ejection fraction (P < .0001), with a greater increase in ferritin and TSAT in HFpEF patients. The left ventricular ejection fraction of the overall series improved by 8 percentage points in both types of HF (from 40% to 48%, P < .0001). The percentage of patients with normalization of right ventricular function increased by 6.9 points (from 74.1% to 81%) in HFpEF patients and by 6.4 points (from 53% to 59.4%) in the HFrEF subgroup (P < .0001). New York Heart Association functional status slightly improved, from a median of 2.4 (interquartile range [IQR]: 2-2.7) to 1.9 (IQR: 1.5-2.5; P < .0001) after FCM in both types of HF. No changes were noted in plasma levels of liver enzymes, creatinine, or natriuretic peptide (P > .05).

Conclusions: Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

Comments: Existing evidence points to iron deficiency as one of the most common comorbidities in heart failure. Iron is an essential micronutrient required for the effective function of the mitochondrion and energy production in cells and tissues. The adverse effects on the contractile function of the cardiomyocytes can be reversible if the iron stores are replenished. Iron supplements are associated with adverse effects and ferric carboxymaltose is relatively safe and has lesser adverse effects. Iron supplementation has proven to be beneficial in both subsets of HF. It had shown to improve LVEF on cardiac magnetic resonance imaging 1 month post supplementation in HFREF. Iron supplementation can be called the fifth pillar in the management of HFREF.

Article 7: Criteria for Defining Stages of Cardiogenic Shock Severity

JACC. 2022, July;80(3);185-198.

Navin K Kapur, Manreet Kanwar, Shashank S Sinha, Katherine L Thayer, A Reshad Garan, Jaime Hernandez-Montfort, Yijing Zhang, Borui Li, Paulina Baca, Fatou Dieng, Neil M Harwani, Jacob Abraham, Gavin Hickey, Sandeep Nathan, Detlef Wencker, Shelley Hall, Andrew Schwartzman, Wissam Khalife, Song Li, Claudius Mahr, Ju H Kim, Esther Vorovich, Evan H Whitehead, Vanessa Blumer, and Daniel Burkhoff.

Abstract

Background: Risk-stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks uniform criteria defining each stage.

Objectives: The purpose of this study was to test parameters that define SCAI stages and explore their utility as predictors of in-hospital mortality in CS.

Methods: The CS Working Group registry includes patients from 17 hospitals enrolled between 2016 and 2021 and was used to define clinical profiles for CS. We selected parameters of hypotension and hypoperfusion and treatment intensity, confirmed their association with mortality, then defined formal criteria for each stage, and tested the association between both baseline and maximum stage and mortality.

Results: Of 3,455 patients, CS was caused by heart failure (52%) or myocardial infarction (32%). Mortality was 35% for the total cohort and higher among patients with myocardial infarction, out-of-hospital cardiac arrest, and treatment with increasing numbers of drugs and devices. Systolic blood pressure, lactate level, alanine transaminase level, and systemic pH were significantly associated with mortality and were used to define each stage. Using these criteria, baseline and maximum stages were significantly associated with mortality (n ¼ 1,890). The lower baseline stage was associated with a higher incidence of stage escalation and a shorter duration of time to reach the maximum stage.

Conclusions: We report a novel approach to defining SCAI stages and identify a significant association between baseline and maximum stage and mortality. This approach may improve the clinical application of the staging system and provides new insight into the trajectory of hospitalized CS patients.

Comments: This study evaluated the easily available parameters at the time of admission and course of hospital stay in defining the stages of cardiogenic shock as per the SCAI system. When analyzed the cardiogenic shock associated with myocardial infarction has more mortality than associated with heart failure, an out-of-hospital cardiac arrest has an increased association with mortality, and increased or intensified treatment is associated with increased mortality. The clinical applicability of the SCAI CS classification is impractical as the cut-off values were not assigned in each class. Most of the ambiguity occurs around stage B. This study incorporated the use of the variables, including treatment intensity (vasoactive agents, inotropes, and assisted mechanical circulatory devices), out-of-hospital cardiac arrest (OHCA), and specific cut-off values for noninvasive hemodynamic (SBP) and laboratory data (lactate, ALT, and pH) to classify patients into the individual stages. These parameters are available bedside making it feasible for application. This approach allows the clinicians to risk-stratify CS patients into SCAI stages using consistent, uniform definitions of hypotension, and hypoperfusion. External validation is required before incorporation into the guidelines.

Lipidology

Article 8: Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction

The PACMAN-AMI Randomized Clinical Trial

JAMA. 2022;327(18):1771-1781.

Abstract

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin Kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown.

Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction.

Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrolment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals.

Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 h after the urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg).

Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 noninfarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy endpoint was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary endpoints were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52.

Results: Among 300 randomized patients (mean [standard deviation {SD}] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, the mean change in percent atheroma volume was −2.13% with alirocumab vs −0.92% with placebo (difference, −1.21% [95% CI, −1.78% to −0.65%], P < .001). The mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs −37.60 with placebo (difference, −41.24 [95% CI, −70.71 to −11.77]; P = .006). The mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving a placebo.

Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in noninfarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population.

Comments: PACMAN-AMI provides evidence that an early, aggressive combination lipid-lowering strategy with PCSK9i treatment on a background of statin therapy for high-risk patients may be beneficial. These results provide further insight into the concept that suggests the degree of LDL-C lowering may lead to favorable changes in the coronary plaque. However, the effect of reduction in plaque volume and changes in characteristics of plaque on clinical outcomes has not yet been demonstrated, so further research is needed to validate these findings. The alirocumab takes a bite out of the coronary plaque (PACMAN).

Interventional Cardiology

Article 9: Predicting Periprocedural Complications in Chronic Total Occlusion Percutaneous Coronary Intervention: The PROGRESS-CTO Complication Scores

JACC: Cardiovascular Interventions. 2022;15(14):1413-1422.

Bahadir Simsek, Spyridon Kostantinis, Judit Karacsonyi, Khaldoon Alaswad, Oleg Krestyaninov, Dmitrii Khelimskii, Rhian Davies, Jeremy Rier, Omer Goktekin, Sevket Gorgulu, Ahmed ElGuindy, Raj H Chandwaney, Mitul Patel, Nidal Abi Rafeh, Dimitrios Karmpaliotis, Amirali Masoumi, Jaikirshan J Khatri, Farouq A Jaffer, Darshan Doshi, Paul B Poommipanit, Bavana V Rangan, Yader Sanvodal, James W Choi, Basem Elbarouni, William Nicholson, Wissam A Jaber, Stephane Rinfret, Michael Koutouzis, Ioannis Tsiafoutis, Robert W Yeh, M Nicholas Burke, Salman Allana, Olga C Mastrodemos, and Emmanouil S Brilakis.

Abstract

Background : Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with an increased risk of periprocedural complications. Estimating the risk of complications facilitates risk-benefit assessment and procedural planning.

Objectives: This study sought to develop risk scores for in-hospital major adverse cardiovascular events (MACE), mortality, pericardiocentesis, and acute myocardial infarction (MI) in patients undergoing CTO PCI.

Methods: The study analyzed the PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) and created risk scores for MACE, mortality, pericardiocentesis, and acute MI. Logistic regression prediction modeling was used to identify independently associated variables, and models were internally validated with bootstrapping.

Results: The incidence of periprocedural complications among 10,480 CTO PCIs was as follows: MACE 215 (2.05%), mortality 47 (0.45%), pericardiocentesis 83 (1.08%), and acute MI 66 (0.63%). The final model for MACE included $65 years of age (1 point), moderate-severe calcification (1 point), blunt stump (1 point), antegrade dissection and re-entry (ADR) (1 point), female (2 points), and retrograde (2 points); the final model for mortality included $65 years of age (1 point), left ventricular ejection fraction <45% (1 point), moderate-severe calcification (1 point), ADR (1 point), and retrograde (1 point); the final model for pericardiocentesis included $65 years of age (1 point), female (1 point), moderate-severe calcification (1 point), ADR (1 point), and retrograde (2 points); the final model for acute MI included prior coronary artery bypass graft surgery (1 point), atrial fibrillation (1 point), and blunt stump (1 point). The C-statistics of the models were 0.74, 0.80, 0.78, and 0.72 for MACE, mortality, pericardiocentesis, and acute MI, respectively.

Conclusions: The PROGRESS-CTO complication risk scores can facilitate the estimation of the periprocedural complication risk in patients undergoing CTO PCI.

Comments: Chronic total occlusion (CTO) interventions are associated with complications. Assessment of the risk-benefit ratio is of need before intervening the CTO. The recent guidelines have decreased the class of recommendation from IIa to IIb for CTOs. Most of the available scores assess the technical success of CTOs, only a few tools assess the risk of complications one of which is the PROGRESS CTO score. Developing scores to assess the risk of MACE, MI, and mortality are important. An older age, moderate-severe calcification, and the use of ADR or the retrograde approach were independently associated with a higher risk of MACE, death, and pericardiocentesis. The CTO length was not associated with any MACE, instead, the blunt stump was associated with increased MACE. Female sex was associated with MACE and pericardiocentesis. The 4 scores (PROGRESS CTO complication risk scores for MI, Mortality, Pericardiocentesis, and Acute MI) will help in having a clear view regarding the complications while intervening in CTO cases unlike the already available scores which focus on the success of crossing and intervening CTO. External validation of scores is of need before incorporating them into the guidelines.

Cardiac Surgery

Article 10: Analysis of Anticoagulation Therapy and Anticoagulation-Related Outcomes Among Asian Patients After Mechanical Valve Replacement

JAMA Netw Open. 2022 Feb 1;5(2):e2146026.

Jo-Ting Huang, Yi-Hsin Chan, Victor Chien-Chia Wu, Yu-Ting Cheng, Dong-Yi Chen, Chia-Pin Lin, Kuo-Chun Hung, Shang-Hung Chang, Pao-Hsien Chu, An-Hsun Chou, and Shao-Wei Chen.

Abstract

Importance: Current international normalized ratio (INR) guidelines are based on trials involving European and US populations. To our knowledge, no adequate study involving Asian patients has been conducted to date.

Objective: To evaluate the association between INR and anticoagulation-related outcomes in an Asian population after mechanical aortic valve replacement (AVR) or mitral VR (MVR).

Design, Setting, and Participants: This retrospective cohort study was conducted between 2001 and 2018, with follow-up until December 31, 2018, among patients who underwent AVR, MVR, or combined AVR-MVR at 3 medical centers and 4 regional hospitals and contributed electronic medical records to the Chang Gung Research Database. Exclusion criteria were missing demographic characteristics, younger than 20 years, fewer than 2 INR records, and having died during the hospitalization of the index surgery.

Main Outcomes and Measures: Bleeding and thromboembolic complications were analyzed. The possibility of nonlinearity and cut-off potential for the INR was explored using a logistic regression model, which considered the INR a restricted cubic spline (RCS) variable.

Results: The study population consisted of 900 patients, with 525 (58.3%) men and 375 (41.7%) women and a mean (standard deviation) age of 52.0 (12.5) years. Overall, 474 (52.7%) received AVR alone, 329 (36.6%) received MVR alone, and 97 (10.8%) received combined AVR-MVR. All patients had at least 2 INR examinations after discharge, providing 16 676 INR records for the AVR group and 18 207 for the MVR and combined AVR-MVR groups. In the AVR group, the RCS model showed that higher risks of composite thromboembolic events were associated with an INR of less than 2.0 or greater than 2.6 vs an INR of 2.0, and a higher risk of bleeding events was associated with an INR of less than 1.8 or greater than 2.4 vs an INR of 2.0. When treating the INR as a categorical variable, the risk of composite thromboembolic and composite bleeding events was significantly higher among patients with INRs less than 1.5 (adjusted odds ratio [aOR], 2.55; 95% confidence interval [CI], 1.37-4.73) and with INRs of 3.0 or greater (aOR, 3.48; 95% CI, 1.95-6.23) vs those with INRs between 2.0 and 2.5. In the MVR and combined AVR-MVR groups, higher risks of composite thromboembolic events were associated with an INR of less than 2.1 or greater than 2.7 vs an INR of 2.5, and a higher risk of bleeding events was associated with an INR of less than 2.1 or greater than 2.8 vs an INR of 2.5. When treating the INR as a categorical variable, the risk of composite bleeding events was significantly higher among patients with INRs of 3.5 or greater (aOR, 2.25; 95% CI, 1.35-3.76) vs those with INRs between 2.5 and 3.0.

Conclusions and Relevance: Among Asian patients in this study, the incidence of thromboembolic events in the MVR group with INRs in the range of 2.0 to 2.5 was not significantly higher than that among those with INRs in the range of 2.5 to 3.0; in the AVR group, the incidence for those with INRs in 1.5 to 2.0 range was not significantly higher than for those with INRs in the range of 2.0 to 2.5.

Comments: This study emphasizes that the INR target values be reframed for the south Asian population. The low INR attained in south Asians was not associated with increased thrombotic complications compared to those with high target INR both at the mitral and aortic position. Low INR essentially does not mean low efficacy in this trial.

Preventive Cardiology

Article 11: Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium

J Am Coll Cardiol Img. 2022 Jul;15(7):1259-1270.

Alexander C Razavi, SM IftekharUddin, Zeina A Dardari, Daniel S Berman, Matthew J Budoff, Michael D Miedema, Albert D Osei, Olufunmilayo H Obisesan, Khurram Nasir, Alan Rozanski, John A Rumberger, Leslee J Shaw, Laurence S Sperling, Seamus P Whelton, Martin Bødtker Mortensen, Michael J Blaha, and Omar Dzaye.

Abstract

Background: Coronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.

Objectives: SCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.

Methods: The authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors.

Results: The mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend <.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% confidence interval [CI]: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (∇C-statistic =+0.046; P = .02) and 7.5% to 20% (∇C-statistic =+0.069; P = .003), which were larger when compared with persons with a 10-year risk >20% (∇C-statistic =+0.01; P = .54).

Conclusions: Higher CAC burden is strongly associated with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

Comments: This trial shows that assessment of coronary artery calcium (CAC) in middle-aged adults with intermediate risk of CAD helps in risk assessment for sudden cardiac death (SCD). A logarithmic association with SCD was noted with a value >100. However, this trial has some limitations which should be considered before applying in the daily practice. It cannot be applied to young adults, and varied populations (most of the studied population were whites). Assessment of the significance of CAC plus LVEF in SCD assessment in ischemic heart disease than either alone would be more helpful.

Electrophysiology

Article 12: Simplified Integrated Clinical and Electrocardiographic Algorithm for Differentiation of Wide QRS Complex Tachycardia The Basel Algorithm

J Am Coll Cardiol EP. 2022 Jul;8(7):831-839.

Federico Moccetti, Mrinal Yadava, Yllka Latifi, Ivo Strebel, Nikola Pavlovic, Sven Knecht, Babken Asatryan, Beat Schaer, Michael Kühne, Charles A Henrikson, Frank-Peter Stephan, Stefan Osswald, Christian Sticherling, and Tobias Reichlin.

Abstract

Background: Prompt differential diagnosis of wide QRS complex tachycardia (WCT) is crucial to patient management. However, distinguishing ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with wide QRS complexes remains problematic, especially for nonelectrophysiologists.

Objectives: This study aimed to develop a simple-to-use algorithm with the integration of clinical and electrocardiographic (ECG) parameters for the differential diagnosis of WCT.

Methods: The 12-lead ECGs of 206 monomorphic WCTs (153 VT, 53 SVT) with electrophysiology-confirmed diagnoses were analyzed. In the novel Basel algorithm, VT has been diagnosed in the presence of at least 2 of the following criteria: (a) clinical high-risk features, (b) lead II time to first peak >40 ms, and (c) lead aVR time to first 
peak >40 ms. The algorithm was externally validated in 203 consecutive WCT cases (151 VT, 52 SVT). Its diagnostic performance and clinical applicability were compared with those of the Brugada and Vereckei algorithms.

Results: The Basel algorithm showed a sensitivity, specificity, and accuracy of 92%, 89%, and 91%, respec­tively, in the derivation cohort and 93%, 90%, and 93%, respectively, in the validation cohort. There were no significant differences in the performance characteristics between the 3 algorithms. The evaluation of the clinical applicability of the Basel algorithm showed similar diagnostic accuracy compared with the Brugada algorithm (80% vs 81%; P ¼ 1.00), but superiority compared with the Vereckei algorithm (72%; P ¼ 0.03). The Basel algorithm, however, enabled a faster diagnosis (median 36 s vs 105 s for the Brugada algorithm [P ¼ 0.002] and 50 s for the Vereckei algorithm [P ¼ 0.02]).

Conclusions: The novel Basel algorithm based on simple clinical and ECG criteria allows for a rapid and accurate differential diagnosis of WCT.

Comments: The assessment of wide QRS complex tachycardia is of importance because of the fear of missing a VT, which needs prompt treatment to prevent mortality compared to the SVT. Several scores have been developed and were validated empirically and not in an orderly fashion. The new algorithm uses only 2 leads, but more importantly, it is a combination of both clinical and electrocardiographic, whereas the Brugada algorithm is purely based on electrocardiography. The new algorithm holds good concerning the sensitivity and specificity when compared to the Brugada algorithm but more than the Vereckei algorithm. The pretest probability of the cardiac disease makes the present score valid and more appropriate for clinical application when compared to the other 2 scores.