Rhythmos is a quarterly medical journal, aiming at apprising colleagues and readers of the latest events and developments in Cardiac Electrophysiology and Pacing and in General Cardiology. It publishes editorials, reviews, interviews, original articles, case reports, images in Cardiology and cardiovascular news. Manuscripts should be submitted online to undergo the peer-review process at our website: www.rhythmos.gr/. The Journal is using the Open Journal Systems and all papers are available to all readers in the pdf format.
Authors who publish with this journal agree to the following terms: a. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. b. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. c. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
Cardiology News / Recent Literature Review / Third Quarter 2022
HCS, 43rd International Congress of Cardiology, Athens, 20-22/10/22 NY Cardiovascular Symposium 2022, New York, NY, USA, 9-11/12/22 AF Symposium, Boston, MA, USA, 2-4/2/2023 ACC Annual Meeting, New Orleans, LA, USA, 4-6/3/23 EHRA Annual Meeting, Barcelona, Spain, 16-18/4/23 Euro PCR 2023, Paris, 16-19/5/2023 HRS Annual Meeting, New Orleans, LA, USA, 19-21/5/23 EMPEROR-Preserved: Empagliflozin Reduced Cardiovascular Disease (CVD) and Heart Failure (HF) Hospitalizations (HFH) and Improved Symptoms Across a Wide Age Range / High age was not Associated with Decreased Efficacy or Intolerability The relationship of age and empagliflozin effects was evaluated in the EMPEROR-Preserved trial. Patients (N=5,988) were grouped according to their baseline age (<65 years, n = 1,199; 65-74 years, n = 2,214; 75-79 years, n = 1,276; ≥80 years, n = 1,299). The incidence of primary outcomes (CVD or HFH) (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years or >80 years. Empagliflozin improved Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction. There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups. Thus, empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age did not reduce efficacy or meaningful intolerability (Bohm M et al, J Am Coll Cardiol 2022;80:1-18). ARIC Study: Adult Cancer Survivors Have Higher Risk of CVD, Especially HF, Independent of Traditional CV Risk Factors A prospective community-based study including 12,414 ARIC (Atherosclerosis Risk In Communities) study participants (mean age 54 years, 55% female, 25% Black), of whom 3,250 (25%) had incident cancer over a median 13.6 years, indicated that age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for CV risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37), HF (HR: 1.52), and stroke (HR: 1.22), but not CAD (HR: 1.11). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk (Florido R et al, J Am Coll Cardiol 2022;80:22–32). VALOR-HCM Study: In Obstructive Hypertrophic Cardiomyopathy (OHCM) Patients With Intractable Symptoms, Mavacamten Reduced the Fraction of Patients Meeting Guideline Criteria for Septal Reduction Therapy (SRT) After 16 Weeks Patients (N=112; age 60 ± 12 years, 51% men, 93% NYHA class III/IV) with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient −37.2 mm Hg; ≥1 NYHA class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53 (Desai MY et al, J Am Coll Cardiol 2022;80:95–108)... (excerpt)
Electroanatomical Mapping to Curtail Heart Block Occurrence and Enhance Safety During Slow Pathway Ablation in Patients with Atrioventricular Nodal Reentrant Tachycardia
A case is presented of use of electro-anatomical mapping (EAM)-guided ablation of a slow pathway in a patient with symptomatic atrioventricular (AV) nodal reentrant tachycardia (AVNRT) as a safeguard against inadvertent AV block. Rhythmos 2022;17(4):79-80.
Pulsed Field Ablation (PFA) for Pulmonary Vein Isolation in τhe Treatment οf Atrial Fibrillation
Pulsed‐field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF). Pulmonary vein isolation (PVI) remains the most frequently used treatment strategy of any AF ablation procedure. A major limitation of current catheter ablation procedures is PVI reconnection, reported to be about 20% of patients. Pulsed field ablation is a novel energy source by which high-voltage electric pulses are used to create pores in the cellular membrane (i.e., electroporation), leading to cellular death. The amount of energy required to produce irreversible electroporation is highly tissue dependent reducing the risk of damage to surrounding non-cardiac tissues. The tissue specificity of PFA may result in a wide therapeutic range and improved safety profile during atrial fibrillation ablation. There has been no evidence of incidental phrenic nerve injury, and finally, PFA has been shown not to injure esophageal tissue when directly applied to the esophagus or indirectly through ablation in the left atrium. Rhythmos 2022;17(4): 75-78.
Left Bundle Branch (LBB) Area Pacing for Cardiac Resynchronization Therapy (CRT): Most Promising Alternative CRT Pacing Modality
Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP) has benefitted a large group of heart failure (HF) patients with low (<35%) left ventricular (LV) ejection fraction (LVEF) and cardiac dyssynchrony, mostly in the form of left bundle branch (LBB) block, conferring amelioration of their HF symptoms and prolongation of their survival. However, it entails a tedious procedure to place and find a stable and functional position of the LV lead in a coronary sinus tributary, which may fail in a considerable percentage of patients, while up to one third of patients, even then, may turn out to be non-responders. Over the recent years, strong new data from observational studies and meta-analyses have shown the safety and feasibility of LBB area pacing (LBBAP) in patients with bradyarrhythmias and most importantly in HF patients in need for CRT. LBBAP yields satisfactory pacing threshold and R wave sensing and low complication rates. Particularly, in patients with CRT indication, LBBAP, as an alternative approach to CRT, has shown significant improvement of functional class and LVEF during short-and mid-term follow-up. Thus, LBBAP, as a relatively novel CRT modality, demonstrates a most promising potential (equivalent or even superior) role for effective CRT for HF patients in need of a viable alternative to BiVP, and also circumvents certain limitations of His bundle pacing, which is another, albeit potentially problematic, mode of CRT. Nevertheless, we are still in dire need for confirmatory data from properly designed randomized controlled trials to further establish the role and value of this alternative CRT pacing modality. Rhythmos 2022;17(4): 71-74.
Cardiology News / Recent Literature Review / Second Quarter 2022
ESC Meeting, Barcelona, Spain, 26-29/8/2022 TCT 22, Boston, MA, USA, 16-20/9/22 HCS, 43rd International Congress of Cardiology, Athens, 20-22/10/22 NY Cardiovascular Symposium 2022, New York, NY, USA, 9-11/12/22 AF Symposium, Boston, MA, USA, 2-4/2/2023 ACC Annual Meeting, New Orleans, LA, USA, 4-6/3/23 EHRA Annual Meeting, Barcelona, Spain, 16-18/4/23 Euro PCR 2023, Paris, 16-19/5/2023 HRS Annual Meeting, New Orleans, LA, USA, 19-21/5/23 Registry Study: In Patients With Multivessel Disease After Revascularization by PCI or CABG, Mildly Decreased Renal Function Did not Increase the Risk of the Primary Composite Outcome (Death, MI, or Stroke) and Mortality / Comparative Outcomes After PCI and CABG Were Similar in the Borderline-Risk Group Among 10,354 eligible patients in a registry who underwent coronary revascularization, classified into 3 groups (stage I, n = 3,735, normal renal function; stage II, n = 5,122, mild dysfunction; and stage III, n = 1,497, moderate dysfunction), after propensity matching, the risk for primary composite outcome was not different between the stage I and the stage II group (HR: 1.12). However, the risk of the primary outcome was higher in the stage III group than in the stage I group (HR: 1.50). The relative effect of PCI vs CABG for the primary outcome was similar in the matched cohort of each renal function group of stages I, II, and III (Kim TO et al, J Am Coll Cardiol 2022;79:1270-84). 2-Cohort Studies: Long-Term Cumulative BP Was Associated With Subsequent Cognitive Decline, Dementia Risk, and All-Cause Mortality in Cognitively Healthy Adults Aged ≥50 Years / Efforts are Needed to Control Long-Term Systolic BP and Pulse Pressure and Maintain Adequate Diastolic BP Data from the HRS (Health and Retirement Study, n=9,294, 45% men, median age 65 y) and ELSA (English Longitudinal Study of Ageing, n=7,566, 40% men, median age 62 y) indicated that over a median follow-up of 8 years each, elevated cumulative systolic BP and pulse pressure were independently associated with accelerated cognitive decline (P< 0.001 for both), elevated dementia risk (P< 0.001 for both), and all-cause mortality (P< 0.001 for both), while a significant inverse association was observed for diastolic BP. Strong dose-response relationships were identified, with similar results for the 2 cohorts. (Li C et al, J Am Coll Cardiol 2022;79:1321–35). The BIOSIGNAL Study: MR-proANP is a Valid Biomarker to Determine Risk of Newly Diagnosed Atrial Fibrillation (NDAF) and MACE in Patients With Acute Ischemic Stroke (AIS) and Can Be Used as a Decision Tool to Identify Patients for Prolonged Cardiac Monitoring Among 1,759 patients Log10MR-proANP levels were associated with cardioembolic (CE) stroke (OR: 7.96; risk ratio: 3.12), as well as NDAF (OR: 35.3; risk ratio: 11.47), and MACE (subdistributional HR: 2.02) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81, was well calibrated, and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA2DS2-VASc score) (Schweizer J et al, J Am Coll Cardiol 2022;79: 1369–81)... (excerpt)
Several portable devices for ECG acquisition are already available in the market and have provided valuable information regarding various cardiac arrhythmias, most commonly atrial fibrillation (AF). Such gadgets are easy to use and can impact health care for both diagnosis and management in a variety of clinical settings, such as in patients complaining of palpitations, patients presenting with unexplained presyncope or syncope, patients with heart failure and suspected tachycardiomyopathy, those afflicted by cryptogenic stroke, and/or patient groups who are at high arrhythmic risk (e.g., older persons, individuals with obesity, sleep apnea, hypertension, diabetes or structural heart disease). Rhythmos 2022; 17(3):58-61.
Aortic Valve Stenosis and Cardiac Amyloidosis: An Underestimated Coexistence
Coexistence of aortic valve stenosis (AS) and cardiac amyloidosis (CA) is frequent in the elderly as both conditions increase with age. Wild type transthyretin (TTR) amyloidosis is the most common type of amyloidosis in AS cohorts. Cardiac amyloidosis and AS share common clinical characteristics making diagnosis of dual pathology challenging. However, certain features should raise suspicion of CA presence in AS patients leading to specific imaging modalities to confirm diagnosis. Dual pathology (AS & CA) increase mortality risk and prompt diagnosis is crucial. Novel pharmacological agents targeted for TTR CA should be initiated to improve prognosis. The role of the Heart Team for decision-making in these cases regarding the optimal management of AS is crucial. Transcatheter aortic valve replacement may be the preferred procedure in these high-risk patients. Rhythmos2022;17(3): 53-57.
COVID-19 Re-Infections: More Common with the Omicron Variant / COVID-19 Pandemic: Is There Light at the End of the Tunnel?
A recent surge of COVID-19 reinfections has been ascribed to new variants of concern (VOCs) with increased transmissibility, such as the Omicron variant, but also to laxity in compliance with measures of prophylaxis, incomplete or lack of vaccination, the Peltzman effect where people tend to increase their risky behavior when safety measures are mandated, weaker antibody responses after booster immunization in some individuals and/or immunocompromised patients, and increased antigen variability in VOCs. The latter impairs humoral and cellular immunity post-infection rendering COVID-19 convalescents more vulnerable and at risk of re-infection with VOCs. Unfortunately, COVID-19 disease is here to stay demanding observance of measures of prophylaxis, expansion of vaccination programs and continued vigilance; there is still a dire need for the development of durably effective vaccines against SARS-CoV-2 but also against its emerging variants. Rhythmos 2022;17(3): 46-52.
COVID-19; SARS-CoV-2; reinfections; COVID-19 vaccines; variants of concern; Omicron variant
Cardiology News / Recent Literature Review / First Quarter 2022
ACC.22, Washington, DC, USA, 2-4/4/22 EHRA 22, Copenhagen, Denmark, 3-5/4/22 HRS 22, San Francisco, CA, USA, 29/4-1/5/22 EuroPCR, Paris, France, 17-20/5/22 ESC Meeting, Barcelona, Spain, 26-29/8/2022 TCT 22, Boston, MA, USA, 16-20/9/22 PRAGUE-17: Left Atrial Appendage Closure (LAAC) Remains Noninferior to DOACs for Preventing Major CV, Neurological, or Bleeding Events / Nonprocedural Bleeding Was Significantly Reduced With LAAC A total of 402 patients with AF (201 per group, age 73.3±7.0 years, 65.7% male, CHA2DS2-VASc 4.7±1.5, HASBLED 3.1±0.9) were randomized to percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban). After a median of 3.5 years, LAAC was noninferior to DOACs for the primary endpoint (composite of cardioembolic events-i.e., stroke, TIA, or systemic embolism-, CV death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only)), by modified intention-to-treat (sub-distribution HR [sHR]: 0.81; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint the corresponding sHRs were 0.68 (P= 0.19) for CV death, 1.14 (P=0.72) for all-stroke/TIA, 0.75 (P=0.28) for clinically relevant bleeding, and 0.55 (P=0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; P=0.25) and on-treatment (sHR: 0.82; P=0.30) analyses (Osmancik P et al, J Am Coll Cardiol 2022;79:1-14). Higher Olive Oil Intake Conferred Lower Risk of Total and Cause-Specific Mortality / Replacing Margarine, Butter, Mayonnaise, and Dairy Fat with Olive Oil Lowered Mortality Among 60,582 women (Nurses’ Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular (CV) disease or cancer, over 28 years, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among persons who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 compared with those who never or rarely consumed olive oil. Higher olive oil intake conferred a 19% lower risk of CV mortality (HR: 0.81), 17% lower risk of cancer mortality (HR: 0.83), 29% lower risk of neurodegenerative disease mortality (HR: 0.71), and 18% lower risk of respiratory disease mortality (HR: 0.82). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil conferred 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined (Guasch-Ferré M et al, J Am Coll Cardiol 2022;79:101–112)... (excerpt)
Midventricular Obstructive Hypertrophic Cardiomyopathy with Apical Aneurysm: Left Ventricular Hemodynamic and Angiographic Findings
A case of a 50-year-old patient with a midventricular obstructive hypertrophic cardiomyopathy is presented and the left ventricular hemodynamic and angiographic findings are depicted and discussed. Rhythmos 2022; 17(2):36-38.
The current guideline recommendations regarding myocardial revascularization of patients with multivessel coronary artery disease (CAD) mostly advocate coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI), especially for patients with diabetes. However, in certain clinical cases, PCI can be considered. FAME and FAME 2 studies had demonstrated the superiority of fractional flow reserve (FFR)-guided PCI over angiography-guided PCI and over optimal medical therapy (OMT) alone respectively. FAME 3 study (Fractional Flow Reserve versus Angiography for Multivessel Evaluation), published early in 2022, was a study that investigated how PCI guided by FFR measurements can perform compared to CABG guided mostly by coronary angiography for the revascularization of patients with three-vessel CAD. Stable patients with an average SYNTAX score of 26 were randomized, while patients with left main disease, recent ST segment elevation myocardial infarction (STEMI), left ventricular ejection fraction <30% or cardiogenic shock were excluded. Regarding the composite primary endpoint of major adverse cardiovascular events (MACE), including death, non-fatal myocardial infarction, stroke or repeat revascularization, at 1 year follow-up, FFR-guided PCI failed to be proven as non-inferior compared to CABG. The findings of FAME 3 as added to those of FAME and FAME 2 should be considered in the context of current guidelines for myocardial revascularization and do not seem practice changing. Relevant limitations, possible implications and future perspectives are also briefly discussed herein. Rhythmos 2022;17(2): 32-35.
COVID-19 Related Myocarditis: Diagnosis and Management
A comprehensive review of current data on COVID-19 related myocarditis is herein presented. Rhythmos 2022;17(2): 25-31.
Cardiology News / Recent Literature Review / Last Quarter 2021
Recent Cardiology Literature Review (Rhythmos 2022;17(1):107-114. ) Cardiology Meetings: 27th Annual International AF Symposium, 13-15/1/22, New York, NY, USA ACC.22, Washington, DC, USA, 2-4/4/22 EHRA 22, Copenhagen, Denmark, 3-5/4/22 HRS 22, San Francisco, CA, USA, 29/4-1/5/22 EuroPCR, Paris, France, 17-20/5/22 ESC Meeting, Barcelona, Spain, 26-29/8/2022 TCT 22, Boston, MA, USA, 16-20/9/22 Brugada Syndrome (BrS) is Associated With Increased Collagen Content Throughout Both Ventricles, With Maximal Collagen Proportions Observed Within BrS RVOT Epicardium Evaluation of 28 whole hearts from consecutive sudden cardiac death cases attributed to BrS (75% men; median age of death 25 years, death occurred in sleep or at rest in 86%) and 29 hearts from a comparator group comprised of noncardiac deaths (control subjects), showed that the highest proportion of collagen was observed in the epicardial right ventricular outflow tract (RVOT) of the BrS group (23.7%). Ventricular myocardium from BrS decedents demonstrated a higher proportion of collagen compared with controls (ratio 1.45; P<0.001), with no significant interactions with respect to sampling location or tissue layer. There was insufficient evidence to support differences in collagen proportion in SCN5A-positive cases (n=5) vs control subjects (ratio 1.23; P=0.27) (Miles C et al, J Am Coll Cardiol 2021;78:1511–21). XIENCE Short DAPT Program: Among High Bleeding Risk (HBR) Patients Undergoing PCI, 1-Month DAPT, Compared With 3-Month DAPT, Was Associated With Similar Ischemic Outcomes and Lower Bleeding Risk Patients who received 1-month DAPT (XIENCE 28 USA and 28 Global; n=1392) were compared with those on 3-month DAPT (XIENCE 90; n= 1972) using propensity score stratification. The primary endpoint of all-cause mortality or myocardial infarction was similar between the 2 groups (7.3% vs 7.5%; P=0.41). The key secondary endpoint of BARC (Bleeding Academic Research Consortium) type 2-5 bleeding was lower with 1-month DAPT compared with 3-month DAPT (7.6% vs 10%; P=0.012). Major BARC type 3-5 bleeding did not differ at 12 months (3.6% vs 4.7%; P=0.082), but was lower with 1-month DAPT at 90 days (1.0% vs 2.1%; P=0.015) (Valgimigli M et al, J Am Coll Cardiol 2021;78:2060–2072). A Booster (Third Dose) at Least 5 Months After a Second Dose of BNT162b2 Vaccine (Pfizer–BioNTech) Conferred 90% Lower Mortality Due to Covid-19 vs Those Who Did Not Receive a Booster Among 843,208 participants 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio–HR for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (P<0.001) (Arbel R et al, N Engl J Med 2021; 385:2413-2420)... (excerpt)
Endocardial Left Atrial Appendage Occlusion and its Place in Contemporary Management of Atrial Fibrillation
Atrial fibrillation (AF) is the most common arrhythmia, affecting 1-2% of the general population in Western countries and it is a well-known risk factor for cardioembolic ischemic stroke, which increases the risk 4 to 5 times. Stroke is responsible for 14% of all annual deaths and every year 8 million people suffer a stroke in European countries. The standard stroke preventive strategy in patients with AF is the administration of anticoagulants. However, contraindications to these agents are not rare, the use of anticoagulants, especially the vitamin-K antagonists, is quantitatively sub-optimal, and many patients with high thromboembolic risk also have increased bleeding risk. Considering that the most frequent location of intracardiac thrombi associated with AF is the left atrial appendage (LAA), the endocardial occlusion of this structure has emerged as a potential alternative treatment. Rhythmos 2022;17(1): 100-104.
COVID-19 Breakthrough Infections in Vaccinated Individuals
Vaccine breakthrough COVID-19 infections are increasingly occurring in fully vaccinated individuals, who may also spread COVID-19 to others. Hence, one is better protected if one wears a mask and maintaining distancing when in indoor public places. Mild infections pose little risk to vaccinated individuals and their contacts, while they may boost the individual immune responses and thus necessitate only monitoring as a precautionary measure. However, higher infectiousness and transmissibility of viral variants remain worrisome. Variants of concern are overrepresented among post-vaccination breakthrough COVID-19 infections. Identifying subgroups at a high risk for severe breakthrough infections is important in prioritizing early preventive treatment or prophylaxis. Despite a strong protection afforded by vaccination against severe disease, breakthrough infections may still advance to severe or critical illness at not-insignificant rates. The age distribution of patients with severe breakthrough infections is skewed towards older age groups and individuals with underlying comorbidities. All these issues and factors modulating the probability of a breakthrough COVID-19 infection in vaccinated people are herein discussed, and a tabulated list of the recommendations of the World Health Organization on COVID-19 infection prevention and control is also presented. Rhythmos 2022;17(1): 92-99.
Cardiology News / Recent Literature Review / Third Quarter 2021
TCT Meeting, San Francisco, 22-26/10/2021 42nd Panhellenic Congress of Cardiology, Athens, 21-23/10/21 AHA Sessions 2021, Boston, MA, USA, 13-15/10/21 ACC.22, Washington, DC, USA, 2-4/4/22 EuroPCR, Paris, France, 17-20/5/22 Subanalysis of SYNTAXES: In Patients With 3-Vessel and/or Left Main Disease Having PCI or CABG, Those on Optimal Medical Therapy (OMT) at 5 Years Had a Survival Benefit at 10 Years Among 1472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; P=0.002) but had a mortality similar to those on 3 types of medications. Patients having CABG with antiplatelet drug and statin at 5 years had lower 10-year mortality than those without (Kawashima H et al, J Am Coll Cardiol 2021;78:27-38). GALACTIC-HF: In Heart Failure (HF) Patients with Reduced Ejection Fraction (EF), Omecamtiv Mecardil Conferred Greater Benefit as Baseline EF Decreased The risk of the primary composite endpoint (PCE) of time-to-first HF event or CV death in the placebo group was ~1.8-fold greater in the lowest EF (≤22%) vs the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (P=0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF≤22% (n=2,246; HR 0.83) vs patients with EF ≥33% (n=1,750; HR 0.99; P=0.013). The absolute reduction in the PCE increased with decreasing EF (EF≤22%; risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile (Teerlink JR et al, J Am Coll Cardiol 2021;78:97-108). Repurposing Metoprolol for COVID-19-Associated ARDS Appears a Safe and Inexpensive Strategy that Can Alleviate the Burden of the COVID-19 Pandemic Among 20 COVID-19 patients with ARDS on invasive mechanical ventilation randomized to metoprolol (n=12, 15 mg daily for 3 days) or control (n=8, no treatment), patients randomized to metoprolol had significantly fewer neutrophils in bronchoalveolar lavage (BAL) on day 4 (P=0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (P=0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5±7.6 vs 21.9±12.6 days; P=0.17) (Clemente-Moragon A et al, J Am Coll Cardiol 2021;78:1001-11)... (excerpt)
Chronic Atrial Overdrive Pacing to Suppress Recurrences of Atrial Fibrillation
A case of a patient with persistent atrial fibrillation is presented who was electrically cardioverted and was subsequently maintained on chronic overdrive atrial pacing and remained free of arrhythmia recurrences. Rhythmos 2021; 16(4):82-83.
Long QT Syndrome in Athletes: Challenges in the Diagnosis and Management
The long QT syndrome (LQTS) is an inherited channelopathy characterized by a prolonged QT interval without structural heart disease posing a risk of sudden cardiac death. Especially in athletes, diagnosis is sometimes more difficult due to bradycardia and to the QT prolongation induced by the exercise. Based on limited clinical data which tend to demonstrate that exercise, especially swimming, is a trigger for cardiac events, participation in any competitive sports practice is not supported by 2020 European guidelines. However, based on retrospective studies and involving the patient-athlete in shared decision making, the 2015 US guidelines are more lenient. Rhythmos 2021;16(4): 79-81.
Cardiovascular Complications of COVID-19 Vaccination
Currently available COVID-19 vaccines may confer several side-effects, including cardiovascular (CV) adverse effects. Among them, perimyocarditis, acute myocardial infarction, arrhythmias and vaccine-induced immune thrombotic thrombocytopenia (VITT) with multiple vascular beds involved causing cerebral venous sinus thrombosis, splanchnic vein thrombosis, deep vein thrombosis and pulmonary embolism, as well as arterial thrombosis, constitute the most worrisome CV complications. Rhythmos 2021;16(4): 73-78.
Cardiology News / Recent Literature Review / Second Quarter 2021
ESC Digital Congress 27-30/8/2021 TCT Meeting, San Francisco, 22-26/10/2021 42nd Panhellenic Congress of Cardiology, Athens, 21-23/10/21 AHA Scientific Sessions 2021, Boston, MA, USA, 13-15/10/21 ACC.22, Washington, DC, USA, 2-4/4/22 EuroPCR, Paris, France, 17-20/5/22 Systemic Lupus Erythematosus (SLE) Patients Have a Higher Associated Risk of Heart Failure (HF) and Other Cardiovascular (CV) Outcomes Compared with Matched Control Subjects Among 3,411 SLE patients (median age: 44.6 years; 86% women) who were matched with 13,644 controls, over a median of 8.5 years, absolute 10-year risks of outcomes were: HF, 3.71% vs 1.94%; atrial fibrillation, 4.35% vs 2.82%; ischemic stroke, 3.75% vs 1.92%; MI, 2.17% vs 1.49%; venous thromboembolism, 6.03% vs 1.68%; and the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 0.89% vs 0.30% (SLE patients, vs control subjects). SLE with subsequent HF was associated with higher mortality compared with HF without SLE (adjusted hazard ratio: 1.50) (Yafasova A et al, J Am Coll Cardiol 2021;77:1717-27). Worse Long-Term Outcomes of Patients with Late Presentation of ST-Segment Elevation Myocardial Infarction (STEMI) Of 13,707 patients (2011-2015), 5,826 consecutive patients diagnosed with STEMI within 48 h of symptom onset were categorized as late (12-48 h; n = 624) or early (<12 h; n = 5,202) presenters. Late presenters had worse clinical outcomes (180-day mortality: 10.7% vs. 6.8%; 3-year mortality: 16.2% vs. 10.6%; both log-rank p < 0.001), whereas presentation at ≥12 h of symptom onset was not independently associated with increased mortality after STEMI. The use of invasive interventional procedures decreased from the first (<12 h) to the second (12-24 h) 12-h interval of symptom-to-door time (“no primary PCI strategy” increased from 4.9% to 12.4%, and “no PCI” from 2.3% to 6.6%; both p < 0.001). Mortality rates increased from the first to the second 12-h interval of symptom-to-door time (from 6.8% to 11.2% for 180-day mortality; from 10.6% to 17.3% for 3-year mortality; all p < 0.05) (Cho KH et al, J Am Coll Cardiol 2021;77:1859-70). High Dietary Sodium (HS) Intake Increases Plasma Volume, Lowers Standing Plasma Norepinephrine, and Decreases Δ Heart Rate in Patients With Postural Tachycardia Syndrome (POTS) Among 14 POTS patients and 13 healthy control subjects (HC), age 23-49 years, enrolled in a crossover study with 6 days of low (LS) (10 mEq/d) or high sodium (HS) (300 mEq/d) diet, in POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and plasma volume (PV) increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in controls on the HS diet, despite no difference in the measured PV (Garland EM et al, J Am Coll Cardiol 2021; 77:2174-84)... (excerpt)
False Negative Myocardial Perfusion Imaging: Regular Exercise Tolerance Test Coming to the Rescue
A case of a patient with critical coronary artery disease is presented where a regular exercise tolerance test was positive whereas myocardial perfusion imaging was (false) negative. Rhythmos 2021; 16(3):62-64.
Transcatheter Aortic Valve Implantation (TAVI) and Mitral Valve Transcatheter Edge-To-Edge Repair (TEER): Current Frontiers and Horizons
During the last two decades transcatheter aortic valve implantation (TAVI) and mitral valve transcatheter edge-to-edge repair (TEER) have evolved in parallel to provide percutaneous interventional treatment solutions for patients with the two most common valvular heart diseases, aortic stenosis and mitral regurgitation, respectively. Having initially been conceived and used to treat patients considered inoperable, TAVI indications have been expanded to include high operative risk and more recently moderate or even low risk patients. The TAVI techniques have also improved to permit tackling challenging complex anatomies and bioprosthetic valve degeneration and structural failure. Similarly, TEER has been initially used to treat inoperable patients with severe symptomatic primary mitral regurgitation (MR), but recently published data have shown that it can provide benefit in carefully selected patients with refractory to optimal medical treatment (OMT) symptomatic severe secondary MR. Furthermore, apart from TEER with the traditional MitraClip system and its iterations, a second TEER system (Pascal) has provided promising results in initial clinical trials and can alternatively be used. We attempt herein a concise overview of the TAVI and mitral valve TEER current state of play. Rhythmos 2021;16(3): 57-61
Interindividual clinical variability characterizes COVID-19 infection, ranging from no or mild symptoms in >95% of individuals to severe and life-threatening acute respiratory distress syndrome with bilateral pneumonia requiring intensive care unit monitoring in <0.5% of infected individuals. The host genetic background seems to determine the susceptibility and outcome in COVID-19 patients. Several relevant genetic variants and risk genes have been identified, relating to blood type, HLA system, angiotensin converting enzyme and other proteins, cytokines, and other host genetic signals and immune system’s specific response. On the other hand, emerging new variants of the COVID-19 virus with enhanced transmissibility/infectivity and immune escape ability pose new risks, especially if they are going to have an impact on the efficacy of currently available vaccines. All these issues relating to the impact of genetics on COVID-19 selectivity are herein reviewed. Rhythmos 2021;16(3): 48-56.
Cardiology News / Recent Literature Review / First Quarter 2021
EHRA online Congress, 23-25/4/2021 ACC Meeting: Atlanta, 15-17/5/2021 EuroPCR online, 18-20/5/201 ESC Digital Congress 27-30/8/2021 TCT Meeting, San Francisco, 22-26/10/2021 EARLY-AF: Cryoballoon Ablation Lowers Rate of Atrial Fibrillation (AF) Recurrence Among Patients Receiving Initial Treatment for Symptomatic, Paroxysmal AF, Compared With Antiarrhythmic Drug (AAD) Therapy, as Assessed by Continuous Cardiac Rhythm Monitoring Among 303 patients with symptomatic, paroxysmal, untreated AF randomized to catheter ablation with a cryothermy balloon or antiarrhythmic drug (AAD) therapy for initial rhythm control, at 1 year, 66 of 154 patients (42.9%) assigned to ablation had AF recurrence vs 101 of 149 patients (67.8%) assigned to AAD (hazard ratio-HR, 0.48; P<0.001). Symptomatic AF recurred in 11% vs 26.2% (HR, 0.39). The median percentage of time in AF was 0% with ablation and 0.13% with AAD. Serious adverse events occurred in 5 (3.2%) vs 6 patients (4%) (Andrade JG et al, N Engl J Med 2021; 384:305-315). STOP AF First: Cryoballoon Ablation as Initial Therapy was Superior to Drug Therapy for Prevention of Recurrence in Patients With Paroxysmal Atrial Fibrillation (AF) with Uncommon Serious Procedure-Related Adverse Events According to a multicenter trial which randomized 203 patients 18-80 years of age with paroxysmal AF to antiarrhythmic drugs (class I or III agents) (n=99) or pulmonary vein isolation with a cryoballoon (n=104), with initial success of the ablation procedure achieved in 97%, the Kaplan–Meier estimate of treatment success at 1 year was 74.6% in the ablation group and 45% in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan–Meier estimate of the percentage of patients with an event within 12 months, 1.9%) (Wazni OM et al, N Engl J Med 2021; 384:316-324). GALACTIC-HF: Among Patients with Heart Failure and a Reduced Ejection, Those on Omecamtic Mecarbil Had a Lower Incidence of a Composite of a HF Event or Death from Cardiovascular Causes on Placebo Among 8256 patients (in- and out-patients) with symptomatic chronic HF and an ejection fraction of <35% assigned to omecamtiv mecarbil (25-50 mg bid) or placebo, in addition to standard HF therapy, over a median of 21.8 months, a primary-outcome event (composite of a first HF event, i.e. hospitalization or urgent visit for HF, or death from CV causes) occurred in 1523 of 4120 patients (37%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio-HR, 0.92; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from CV causes (HR, 1.01). There was no significant difference between groups in the change from baseline on quality-of-life score. At week 24, the change from baseline for the median N-terminal pro–B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng/L higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar (Teerlink JR et al, N Engl J Med 2021; 384:105-116)... (excerpt)
Cavotricuspid Isthmus Ablation Using a Novel High-Density Automated Electroanatomical Contact Mapping System
A case of atrial flutter ablation is presented with use of a novel high-density automated electroanatomic contact mapping system that was employed for guidance of the procedure. Rhythmos 2021; 16(2):39-40.
Anticoagulation with Enoxaparin in Patients with Obesity
Obesity is a relatively common characteristic in modern western world populations and has a significant impact on the person’s health status. Despite the fact that it constitutes a well-described risk factor for thromboembolic events, the optimal anticoagulation strategy in obese patients remains vague. The available data suggest that while standard fixed enoxaparin doses (for prophylactic purposes) can lead to subtherapeutic effect, the conventional weight-based dosing schemes may result in overtreatment. Although not particularly strong, contemporary evidence indicate that a dose reduction in morbidly obese patients will likely result in a therapeutic anti-Xa level without an increased probability for bleeding or VTE. Rhythmos 2021;16(2):34-38.
COVID-19 Vaccines: Cardiovascular Perspectives
The accelerated development of COVID-19 vaccines has ushered in new hope for the beginning of the end of this unprecedented pandemic with the heaviest toll on global health and economy. The goal of vaccination is to achieve “herd immunity” which helps interrupt the chain of transmission with the threshold of such immunity estimated at 60-70%. There are four main types of COVID-19 vaccines: messenger RNA (mRNA); viral vector; protein-based; and whole virus. mRNA vaccines and most of the COVID-19 vaccines are using various versions of the spike (S) protein as their vaccine antigen component, while a few vaccines employ the whole virion. Local reactions and mild symptoms are the most common adverse reactions to vaccination; however, anaphylaxis is a potentially life-threatening adverse effect and needs to be monitored and promptly managed. Deaths with temporal association with vaccination have also been reported, but not causally linked to vaccination. Thrombotic events have also been reported, particularly with two brands, and have caused alarm but apparently remain extremely rare, nevertheless authorities remain watchful. One is considered fully vaccinated for COVID-19 ≥2 weeks after one has received the last dose. Unfortunately, new strains of COVID-19 are emerging fast, for which the current vaccines may be less effective. Thus, it is still crucial to continue wearing facemasks, apply hand washing, and social distancing in order to slow viral spread and to protect everybody from infection. Several unknowns still remain about COVID-19 vaccines that relate to the safety and efficacy of the vaccines in “special” populations, the degree and duration that these vaccines protect against infection and transmission. and possible long-term adverse effects of vaccination, not yet encountered in phase 3 trials. Rhythmos 2021;16(2): 22-33.
Cardiology News / Recent Literature Review / Last Quarter 2020
Rhythmos 2021;16(1): 14-21. 26th Annual International AF Virtual Symposium, 29-31/1/2021 EHRA online Congress, 23-25/4/2021 ACC Meeting: Atlanta, 15-17/5/2021 EuroPCR online, 18-20/5/201 ESC Digital Congress 27-30/8/2021 TCT Meeting, San Francisco, 22-26/10/2021 Active Myocardial Inflammation is a Powerful Predictor of Recurrent Ventricular Tachycardia (VT) Following Catheter Ablation: VT Ablation Should be Avoided During Active Myocarditis (AM), But is Often of Benefit for Recurrent VT After the Acute Phase of Myocarditis Among 125 consecutive patients (age 51±14 years, 91% men, LVEF 52%±9%) with myocarditis diagnosed by endomyocardial biopsy (59%) and/or cardiac magnetic resonance (90%), undergoing VT ablation, with all patients showing low-voltage areas (LVA) at electro-anatomical map (97% epicardial or endoepicardial), VT recurrences were documented in 25 patients (20%) by 12 months, and in 43 (34%) by last follow-up (median 63 months). At multivariable analysis, active myocarditis (AM) stage was the only predictor of VT recurrences by 12 months (hazard ratio: 9.5; p < 0.001), whereas both AM stage and wide border zone were associated with arrhythmia recurrences anytime during follow-up. No VT episodes were found after redo ablation was performed in 23 patients with previous (non-active) myocarditis (Peretto G et al, J Am Coll Cardiol 2020;76:1644–1656). Left Ventricular (LV) Non-Compaction (LVNC): Vigorous Recreational Physical Activity (VPA) May be a Possible Determinant of LV Hypertrabeculation in Asymptomatic Individuals In PESA (Progression of Early Subclinical Atherosclerosis) study participants (n = 4,184 subjects free of cardiovascular disease), LVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 = 30.5%) than in participants with no VPA (14.2%). The Jacquier and Grothoff criteria were also more frequently fulfilled in participants in the highest VPA quintile (Jacquier Q5 = 27.4% vs no VPA = 12.8% and Grothoff Q5 = 15.8% vs no VPA = 7.1%). The prevalence of the systolic Stacey LVNC criterion was low (3.6%) and did not differ significantly between no VPA and Q5 (de la Chica JA et al, J Am Coll Cardiol 2020;76: 1723–1733). Interleukin-1β (IL-1β) Measured on Admission is Associated with Risk of Premature Death in Patients with Myocardial Infarction IL-1β concentration measured at admission in 1,398 patients with ST-segment elevation MI (STEMI) was associated with all-cause mortality at 90 days (adjusted hazard ratio - adjHR: 1.47 per 1 SD increase; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; p = 0.0002) and at 1 year (adjHR: 1.93; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; p = 0.002, and adjHR: 2.29; p = 0.004, respectively) and at 1 year (adjHR: 2.32; p = 0.002, and adjHR: 2.35; p = 0.001, respectively) (Silvain J et al, J Am Coll Cardiol 2020;76:1763–1773)... (excerpt)
A case of refractory heart failure (HF) is presented in a 64-year-old gentleman with ischemic cardiomyopathy and severe left ventricular dysfunction, who availed himself of currently available hybrid HF treatment, like optimal medical treatment, electrical and interventional therapies comprising drugs, an implantable cardiac resynchronization therapy defibrillator (CRT-D) effected via alternate route (middle cardiac vein) for left ventricular lead placement combined with percutaneous mitral valve therapy (MitraClip) that prolonged his life to ~10 years. Rhythmos 2021; 16(1):11-13.