Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis.

BACKGROUND AND AIMS: Conflicting data are available regarding the association between periprocedural myocardial infarction (PMI) and mortality following percutaneous coronary intervention. The purpose of this study was to evaluate the incidence and prognostic implication of PMI according to the Universal Definition of Myocardial Infarction (UDMI), the Academic Research Consortium (ARC)-2 definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition. METHODS: Studies reporting adjusted effect estimates were systematically searched. The primary outcome was all-cause death, while cardiac death was included as a secondary outcome. Studies defining PMI according to biomarker elevation without further evidence of myocardial ischaemia ('ancillary criteria') were included and reported as 'definition-like'. Data were pooled in a random-effect model. RESULTS: A total of 19 studies and 109 568 patients were included. The incidence of PMI was progressively lower across the UDMI, ARC-2, and SCAI definitions. All PMI definitions were independently associated with all-cause mortality [UDMI: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.32-1.97; I2 34%; ARC-2: HR 2.07, 95% CI 1.40-3.08, I2 0%; SCAI: HR 3.24, 95% CI 2.36-4.44, I2 78%]. Including ancillary criteria in the PMI definitions were associated with an increased prognostic performance in the UDMI but not in the SCAI definition. Data were consistent after evaluation of major sources of heterogeneity. CONCLUSIONS: All currently available international definitions of PMI are associated with an increased risk of all-cause death after percutaneous coronary intervention. The magnitude of this latter association varies according to the sensitivity and prognostic relevance of each definition.

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

BACKGROUND AND AIMS: Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. METHODS: In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. RESULTS: At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. CONCLUSIONS: Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum.

BACKGROUND: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. METHODS: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. RESULTS: MVP was associated with DMR absent/mild (ERO <20 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%-90% range, 0-9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%-90% range, 4-11 versus 0-7) and mediocre correlation (R2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29-1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11-1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02-1.14]) or ≥1% (hazard ratio, 1.11 [1.08-1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10-1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10-1.16], all per 1-point increment with P<0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P<0.0001). CONCLUSIONS: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.

Integrating platelet reactivity in the age, creatinine and ejection fraction score to predict clinical outcomes following percutaneous coronary intervention in patients with chronic coronary syndrome: the PR-ACEF score.

To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up.

The safety of transesophageal echocardiography to guide transcatheter tricuspid valve edge-to-edge repair.

BACKGROUND: Transesophageal echocardiography (TEE) is primarily used to guide transcatheter structural heart interventions, such as tricuspid transcatheter edge-to-edge repair (TEER). Although TEE has a good safety profile, it is still an invasive imaging technique that may be associated with complications, especially when performed during long transcatheter procedures or on frail patients. The aim of this study was to assess TEE-related complications during tricuspid TEER. METHODS: This is a prospective study enrolling 53 patients who underwent tricuspid TEER for severe tricuspid regurgitation (TR). TEE-related complications were assessed clinically and divided into major (life-threatening, major bleeding requiring transfusions or surgery, organ perforation, and persistent dysphagia) and minor (perioral hypesthesia, < 24 h dysphagia/odynophagia, minor intraoral bleeding and hematemesis not requiring transfusion) RESULTS: The median age of the patient population was 79 years; 43.4% had severe, 39.6% massive, and 17.6% torrential TR. 62.3% of patients suffered from upper gastrointestinal disorders. Acute procedural success (APS) was achieved in 88.7% in a median device time of 36 min. A negative association was shown between APS and lead-induced etiology (r = -.284, p = .040), baseline TR grade (r = -.410, p = .002), suboptimal TEE view (r = -.349, p = .012), device time (r = -.234, p = .043), and leaflet detachment (r = -.496, p < .0001). We did not observe any clinical manifest major or minor TEE-related complications during the hospitalization. CONCLUSIONS: Our study reinforces the good safety profile and efficacy of TEE guidance during tricuspid TEER. Adequate preoperative management and intraprocedural precautions are mandatory in order to avoid serious complications. Furthermore, suboptimal intraprocedural TEE views are associated with lower TR reduction rates. HIGHLIGHTS: Transesophageal echocardiography is a crucial and safe technique for guiding transcatheter structural heart interventions. A mix of mid/deep esophageal and trans gastric views, as well as real-time 3D imaging is generally used to guide the procedure. Adequate preoperative management and intraprocedural precautions are mandatory in order to avoid serious problems. A shorter device time is associated with more rarely probe-related complications. Suboptimal intraprocedural TEE views are associated with lower TR reduction rates.

Electrocardiographic alterations in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, and its incidence has grown within several years, quickly becoming the third leading cause of mortality. The disease is characterized by alveolar destruction, air-trapping, and chronic inflammation due to persistent exposure to a large spectrum of harmful particles. The diagnosis of COPD is made by demonstration of persistent and not fully reversible airflow limitation, and different phenotypes may be recognized based on pathophysiological, clinical, and radiological features. However, COPD is a systemic disease with effects involving several organs. For example, mechanical and functional alterations secondary to COPD involve heart function. Indeed, cardiovascular diseases are highly prevalent in patients affected by COPD and represent the primary cause of mortality in such patients. An electrocardiogram is a simple and cheap test that gives much information about the heart status of COPD patients. Consequently, variations from "normality" can be appreciated in these patients, with the most frequent abnormalities being P-wave, QRS axis, and ventricular repolarization abnormalities, in addition to conduction alterations and a vast number of arrhythmias. As a result, ECG should be routinely performed as a valuable tool to recognize alterations due to COPD (i.e., mechanical and functional) and possible associated heart diseases. This review aims to describe the typical ECG features in most COPD patients and to provide a systematic summary that can be used in clinical practice.

Factors influencing post-surgical survival in degenerative mitral regurgitation.

AIMS: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). CONCLUSION: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.

Severe heart failure and intracardiac thrombosis: going beyond the appearance for diagnosis and treatments.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

The current paradigm of cardiac troponin increase among athletes.

Although it is known that exercise improves cardiovascular health and extends life expectancy, a significant number of people may also experience an elevation in cardiac troponin levels as a result of exercise. For many years, researchers have argued whether exercise-induced cardiac troponin rises are a consequence of a physiological or pathological reaction and whether they are clinically significant. Differences in cardiac troponin elevation and cardiac remodeling can be seen between athletes participating in different types of sports. When forecasting the exercise-induced cardiac troponin rise, there are many additional parameters to consider, as there is a large amount of interindividual heterogeneity in the degree of cardiac troponin elevation. Although it was previously believed that cardiac troponin increases in athletes represented a benign phenomenon, numerous recent studies disproved this notion by demonstrating that, in specific individuals, cardiac troponin increases may have clinical and prognostic repercussions. This review aims to examine the role of cardiac troponin in athletes and its role in various sporting contexts. This review also discusses potential prognostic and clinical implications, as well as future research methods, and provides a straightforward step-by-step algorithm to help clinicians interpret cardiac troponin rise in athletes in both ischemic and non-ischemic circumstances.

Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function. METHODS: We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality. RESULTS: Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56-1.34). CONCLUSIONS: SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.

Cardiovascular and metabolic effects of hyperbilirubinemia in a cohort of Italian Olympic athletes.

INTRODUCTION: Bilirubin was supposed to have cardio-metabolic protective role by signaling functions. Indeed, mild hyperbilirubinemia has immunosuppressive and endocrine activities and may offer protection against oxidative stress-mediated diseases. Gilbert syndrome (GS) has been hypothesized to provide cardio-metabolic benefits. OBJECTIVE: To investigate the prevalence of hyperbilirubinemia and its cardio-metabolic effects in a cohort of elite Italian athletes engaged in different sports disciplines. METHODS: We enrolled 1492 elite athletes (age 25.8 ± 5.1) practising different disciplines (power, skills, endurance, and mixed) underwent blood, echocardiographic, and exercise tests. GS was diagnosed per exclusionem in athletes with isolated asymptomatic unconjugated hyperbilirubinemia. RESULTS: GS was highlighted in 91 athletes (6%; globally 9% male and 2.4% female); 82% were males (p < 0.0001) showing higher indirect bilirubin (0.53 ± 0.4 vs. 0.36 ± 0.24 mg/dL in females, p < 0.0001). GS athletes had fewer platelets (201 ± 35 vs. 214 ± 41, p = 0.01), higher iron (male: 124 ± 44 vs. 100.9 ± 34 mcg/dL, p < 0.0001; female: 143.3 ± 35 vs. 99.9 ± 42 mcg/dL, p < 0.0001), and lower erythrocyte sedimentation rate, (1.93 ± 0.9 vs. 2.80 ± 2.7 mm/H, p = 0.03). At multivariate analysis, male (OR 3.89, p = 0.001) and iron (OR 3.47, p = 0.001) were independently associated with GS. No significant differences were found in cardiac remodeling, heart rate, blood pressure, arrhythmias, or power capacity at stress test. Endurance athletes (313) presented higher total (p = 0.003) and indirect bilirubin (p = 0.001). CONCLUSION: Bilirubin has several metabolic effects (including immunosuppressive and endocrine) and plays a role in regulating antioxidant pathways exercise-related with hematological consequences but seems not to affect significantly cardiovascular remodeling. Endurance athletes present higher bilirubin concentrations, likely as an adaptive mechanism to counteract increased oxidative stress.

The butterfly effect: Restoring the tricuspid coaptation after clipping the antero-septal commissure.

Edge-to-edge tricuspid transcatheter repair requires extensive echocardiographic planning before the procedure. Sometimes, anatomic features may anticipate a suboptimal result. For this reason, a tailored strategy is the key to the procedural success. We report a case of massive tricuspid regurgitation due to multiple complex mechanisms that was successfully treated by clipping the antero-septal commissure to restore functional coaptation of the valve leaflets at multiple sites.

Association of transcatheter edge-to-edge repair with improved survival in older patients with severe, symptomatic degenerative mitral regurgitation.

BACKGROUND: Randomized clinical trials demonstrated transcatheter edge-to-edge repair (TEER) efficacy in improving outcome vs. medical management for functional mitral regurgitation, but limited randomized data are available for the treatment of degenerative mitral regurgitation (DMR). We aimed to compare the outcome of older patients treated with TEER vs. unoperated DMR. METHODS AND RESULTS: Registries including consecutive patients ≥65 years with symptomatic severe DMR treated with TEER (MitraSwiss and Minneapolis Heart Institute registries) or unoperated (MIDA registry) were analysed. Survival was compared overall and after matching for age, sex, EuroSCORE II, and ejection fraction. The study included 1187 patients (872 treated with TEER and 315 unoperated). During 24 ± 17 months of follow-up, 430 patients died, 18 ± 1% at 1 year and 50 ± 2% at 4 years. Patients undergoing TEER had similar age (82 ± 6 vs. 82 ± 7 years) and sex to unoperated patients, but higher surgical risk/comorbidity (EuroSCORE II 3.98 ± 4.28% vs. 2.77 ± 2.46%), more symptoms, and atrial fibrillation (P < 0.0001). Transcatheter edge-to-edge repair was associated with lower mortality accounting for age, sex, EuroSCORE II, New York Heart Association class, atrial fibrillation, and ejection fraction [hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.37-0.58; P < 0.0001]. After propensity matching (247 pairs of patients), TEER consistently showed better survival compared with unoperated patients (49 ± 6% vs. 37 ± 3% at 4 years, P < 0.0001) even in comprehensive multivariable analysis (HR: 0.60, 95% CI: 0.40-0.91; P = 0.03). Procedural failure was infrequent but post-procedural mitral regurgitation, remaining moderate-to-severe in 66 (7.6%) patients, was associated with excess mortality vs. trivial residual regurgitation (30 ± 6% vs. 11 ± 1% at 1 year, P < 0.0001). CONCLUSION: Amongst older patients with severe symptomatic DMR at high surgical risk, mitral TEER was associated with higher survival vs. unoperated patients. Successful control of mitral regurgitation was key to survival improvement with mitral TEER, which should be actively considered in patients deemed inoperable.

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets.

Type-2 diabetes mellitus (DM) represents one of the most important risk factors for cardiovascular diseases (CVD). Hyperglycemia and glycemic variability are not the only determinant of the increased cardiovascular (CV) risk in diabetic patients, as a frequent metabolic disorder associated with DM is dyslipidemia, characterized by hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol levels and a shift towards small dense low-density lipoprotein (LDL) cholesterol. This pathological alteration, also called diabetic dyslipidemia, represents a relevant factor which could promotes atherosclerosis and subsequently an increased CV morbidity and mortality. Recently, the introduction of novel antidiabetic agents, such as sodium glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), has been associated with a significant improvement in CV outcomes. Beyond their known action on glycemia, their positive effects on the CV system also seems to be related to an ameliorated lipidic profile. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs and their effects on diabetic dyslipidemia, which could explain the provided global benefit to the cardiovascular system.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

A sudden right-to-left shunt: the importance of evaluating patent foramen ovale during exercise.

A 55-year-old male affected by heart failure with reduced ejection fraction and a history of a transient cerebrovascular accident was accepted to the Cardiology Department for worsening dyspnea. A cardiopulmonary exercise test was performed after therapy optimization to further evaluate exercise intolerance. A rapid increase in the minute ventilation/carbon dioxide production slope, end-tidal oxygen pressure, and respiratory exchange ratio, with a concomitant decrease in end-tidal carbon dioxide pressure and oxygen saturation, were observed during the test. These findings indicate exercise-induced pulmonary hypertension leading to a right-to-left shunt. Subsequent echocardiography with a bubble test unveiled the presence of an unknown patent foramen ovale. It is, therefore, necessary to exclude a right-to-left shunt by cardiopulmonary exercise testing, particularly in patients predisposed to develop pulmonary hypertension during exercise. Indeed, this eventuality might potentially provoke severe cardiovascular embolisms. However, the patent foramen ovale closure in patients with heart failure with reduced ejection fraction is still debated because of its potential hemodynamic worsening.

Simultaneous presence of Brugada and overgrowth syndromes.

In the present article, we describe the case of a 21-year-old male presenting to the emergency department following a syncopal episode. Physical examination revealed a distinctive facial appearance in the context of an overgrowth syndrome. Also, an ajmaline test was performed because of the evidence of an incomplete right bundle branch block with ST-T segment elevation in the right precordial derivations, revealing a type-1 Brugada electrocardiographic pattern. Considering the high cardiovascular risk phenotype, the patient underwent subcutaneous cardiac defibrillator implantation. The subsequent comprehensive genomic testing analysis led to the diagnosis of a variant of uncertain significance of the nuclear receptor binding SET domain protein 1 (NSD1) gene and a heterozygous mutation of the calsequestrin 2 (CASQ2) gene. NSD1 gene alterations are usually responsible for the Sotos syndrome, characterized by distinctive facial appearance, learning disability, and overgrowth, in addition to cardiac anomalies ranging from single self-limiting alterations to more severe, complex cardiac abnormalities. On the contrary, a compound heterozygous or homozygous alteration of the CASQ2 gene is usually associated with catecholaminergic polymorphic ventricular tachycardia; however, the significance of a merely heterozygous alteration in the CASQ2 gene, as in the present case report, is not yet clear. In conclusion, to the best of our knowledge, this is the first description of the coexisting presence of Brugada and overgrowth syndromes in a single patient.

Prevalence and clinical impact of high platelet reactivity in patients with chronic kidney disease treated with percutaneous coronary intervention: An updated systematic review and meta-analysis.

BACKGROUND: High platelet reactivity (HPR) on clopidogrel and chronic kidney disease (CKD) are recognized as potent risk factors for adverse outcomes in patients suffering coronary artery disease (CAD) and undergoing percutaneous coronary intervention (PCI). However, conclusive evidence regarding their reciprocal interaction and the consequent impact on clinical events is still lacking. OBJECTIVES: We performed a metaanalysis with the aim to evaluate the prevalence of HPR in patients with and without CKD and the incidence of major adverse cardiovascular events (MACE) according to the renal and platelet function status in current literature (co-primary endpoints). Secondary endpoints were myocardial infarction (MI), all-cause death, and definite/probable stent thrombosis (ST). METHODS: We searched on PubMed, EMBASE, and Cochrane Library studies investigating CKD and HPR on clopidogrel in patients suffering CAD who underwent PCI and their related outcomes. Overall, 13 studies including 22.464 patients were selected. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using a random-effects model with the Mantel-Haenszel method. RESULTS: Patients with CKD presented significantly higher odds of HPR compared with those without CKD (OR 1.51 [95% CI: 1.29, 1.76]). In patients without CKD, HPR was associated with increased odds of MACE (OR 1.31 [95% CI: 1.01, 1.72]), MI (OR 1.48 [95% CI: 1.17, 1.86]) and definite/probable ST (OR 2.45 [95% CI: 1.08, 5.60]). In patients with CKD, HPR was associated with higher odds of both MACE (OR 1.61 [95% CI: 1.14, 2.27]) and MI (OR 1.69 [95% CI: 1.11, 2.59]), compared to those without HPR. CONCLUSIONS: Our analysis shows that HPR on clopidogrel is more frequent in patients with CKD treated with PCI. Patients with HPR are exposed to a high risk of MACE after PCI, regardless of the renal function status.

Contrast-induced Acute Kidney Injury in Diabetic Patients and SGLT-2 Inhibitors: A Preventive Opportunity or Promoting Element?

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients undergoing diagnostic or therapeutic procedures that require contrast use and negatively affects the long-term outcomes. Patients with type 2 diabetes mellitus (DM), particularly those who have already developed diabetic nephropathy (DN), are more susceptible to contrast-induced renal damage. Indeed, contrast media amplify some pathological molecular and cellular pathways already in place in the DN setting. In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have triggered a paradigm shift in managing patients with type 2 DM, reducing cardiovascular and renal adverse events, and slowing DN development. Some evidence also suggests favorable effects of SGLT2i on acute kidney injury despite the initial alarm; however, little data exist regarding CI-AKI. The present review provides an updated overview of the most recent experimental and clinical studies investigating the beneficial effects of SGLT2i on chronic and acute renal injury, focusing on their potential role in the development of CI-AKI. Thus, we aimed to expand the clinicians' understanding by underscoring new opportunities to prevent this complication in the setting of DM, where effective preventive strategies are still lacking.

Impact of Mediterranean diet on metabolic and inflammatory status of patients with polyvascular atherosclerotic disease.

BACKGROUND AND AIMS: The Mediterranean Diet (MD) represents a key player in cardiovascular disease prevention. Therefore, we aimed to assess the relationship between adherence to the MD and inflammatory, lipid and glycemic profile in patients affected by polyvascular atherosclerotic disease (PAD). We also investigated the incidence of long-term major adverse cardiovascular events (MACEs) according to MD adherence. METHODS AND RESULTS: We enrolled 107 patients with PAD, defined as the simultaneous involvement of at least two vascular districts. Adherence to the MD was estimated through a 9-item simplified form of the Mediterranean Diet Score. Improved fasting glycemic and LDL-cholesterol levels were reported in the high-adherence group compared with the low-adherence group (p < 0.001 and p = 0.0049, respectively). Both C-reactive protein and platelet-to-lymphocyte ratio were significantly lower in high-adherence patients than those with poor adherence to the MD (p = 0.0045 and p = 0.008, respectively). During follow-up (mean 34 ± 11 months), fatal events happened exclusively in the low-adherence group (58%), with an event-free survival of 37% compared with 87% in the moderate-adherence group and 70% in the high-adherence group (log-rank p-value < 0.001). Low adherence to the MD was associated with a higher incidence of MACEs in the Cox regression model adjusted for atherosclerotic risk factors (HR 12.23, 95% CI 4.00-37.39). CONCLUSIONS: High adherence to Mediterranean dietary pattern seems to be associated with improving inflammatory and metabolic status in patients suffering from PAD, potentially translating into better long-term cardiovascular outcomes. These findings provide evidence regarding the relevance of MD as a secondary preventive tool in this high-risk population.