Cardiac Damage Staging Predicts Outcomes in Aortic Valve Stenosis After Aortic Valve Replacement: Meta-Analysis.

Background: The prognostic value of cardiac damage staging classification based on the extent of extravalvular damage has been proposed in moderate/severe aortic stenosis (AS). Objectives: The purpose of this study was to assess the association of cardiac damage staging with mortality across the spectrum of patients with AS following aortic surgical or transcatheter aortic valve replacement (AVR). Methods: We conducted a pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies published through February 2023. Results: In total, 16 studies (n = 14,499) met our eligibility criteria and included 12,282 patients with symptomatic severe AS and 2,217 patients with asymptomatic severe/moderate AS. For patients with symptomatic severe AS, all-cause mortality was 24.0%, 27.7%, 38.0%, 56.3%, and 57.3% at 5 years in patients with cardiac damage stage 0, 1, 2, 3, and 4, respectively (stage 0 as reference; HR in stage 1: 1.30 [95% CI: 1.03-1.64]; P = 0.029; stage 2: 1.74 [95% CI: 1.41-2.16]; P < 0.001; stage 3: 2.92 [95% CI: 2.35-3.64]; P < 0.001, and stage 4: 3.51 [95% CI: 2.79-4.41]; P < 0.001). For patients with asymptomatic moderate/severe AS, all-cause mortality was 19.3%, 36.9%, 51.7%, and 67.8% at 8 years in patients with cardiac damage stage 0, 1, 2, and 3 to 4, respectively (HR in stage 1: 1.70 [95% CI: 1.21-2.38]; P = 0.002; stage 2: 2.20 [95% CI: 1.60-3.02]; P < 0.001; and stage 3 to 4: 3.90 [95% CI: 2.79-5.47]; P < 0.001). Conclusions: In patients undergoing AVR across the symptomatic and severity spectrum of AS, cardiac damage staging at baseline has important prognostic implications. This pooled meta-analysis in patients undergoing AVR suggests that staging of baseline cardiac damage could be considered for timing and selection of therapy in patients with moderate or severe AS to determine the need for earlier AVR or adjunctive pharmacotherapy to prevent irreversible cardiac damage and improve the long-term prognosis.

The Mortality Burden of Untreated Aortic Stenosis.

BACKGROUND: The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe. OBJECTIVES: The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database. METHODS: We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality. RESULTS: Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality. CONCLUSIONS: Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.

The Dicrotic Notch: Mechanisms, Characteristics, and Clinical Correlations.

PURPOSE OF REVIEW: The dicrotic notch (DN) has long been considered a marker of arterial stiffness and compliance. Herein, we explored the recent developments in vascular medicine research in an attempt to assess the DN utility in clinical cardiovascular medicine. RECENT FINDINGS: Since its discovery, several studies have attempted to measure the changes in different parameters of the DN in physiological and pathological states. Despite the significance of their findings, the clinical role of the DN remained limited. This may have been related to the difficulty of measuring the DN via indwelling arterial catheters in the past. However, over the past two decades, several non-invasive methods have been developed, which may re-ignite interest in DN research. The DN may have broader applications in clinical cardiovascular medicine. Further research is needed to establish the accuracy of DN non-invasive measurement methods and compare its prognostic value to other circulatory parameters.

Tissue plasminogen activator for axillary Impella 5.0 with heparin-induced thrombocytopenia as a treatment of choice for acute Impella thrombosis: a case report.

Background: Patients with cardiogenic shock requiring temporary support with percutaneous ventricular assist device, such as Impella (Abiomed, Inc.), can develop heparin-induced thrombocytopenia (HIT) which requires use of alternative purge solution anticoagulation. There are limited recommendations on use of anticoagulation other than standard Unfractionated Heparin in 5% dextrose solution. Case summary: This case describes 69-year-old female who presented with symptoms of decompensated systolic heart failure and was found to be in cardiogenic shock and despite use of inotropes and vasopressors maintained low systolic blood pressure and low mixed venous oxygen saturation which lead to use of axillary Impella 5.0 (Abiomed, Inc.) who developed HIT. Purge solution anticoagulation was switched to Argatroban, but due to increased motor pressures, tissue plasminogen activator (tPA) was successfully used to maintain proper motor pressures. Ultimately, patient was transferred to an outside facility for a transplant evaluation. Discussion: This case demonstrates successful and safe use of tPA as an alternative purge solution although more data needed to support this finding.

Three-Year Outcomes of Balloon-Expandable Transcatheter Aortic Valve Implantation According to Annular Size.

Data on the association between annular size and transcatheter aortic valve implantation (TAVI) outcomes beyond 1 year are limited. The present study assessed the association between the aortic annulus size and TAVI clinical and hemodynamic outcomes at 3 years of follow-up. Patients were classified according to the aortic annulus size as having small, intermediate, and large annuli (size <400, 400 to 574, and ≥575 mm2, respectively). The co-primary endpoints were all-cause mortality and heart failure hospitalization. Further, the changes in hemodynamic outcomes over the follow-up period (median 37, interquartile range: 26 to 45 months) were assessed. The present analysis included 850 patients, with 182 patients (21.4%), 538 patients (63.3%), and 130 patients (15.3%) in the small, intermediate, and large-sized aortic annulus groups, respectively. The groups had comparable age and pre-TAVI pressure gradients; however, patients with small annuli had higher Society of Thoracic Surgeons risk scores. Adjusted Cox regression analysis showed that compared to patients with intermediate-sized annuli, patients with small and large annuli had similar all-cause mortality (hazard ratio [HR] = 1.11, 95% confidence interval [CI] 0.72 to 1.69 and HR = 0.74, 95% CI 0.48 to 1.16, respectively) and heart failure hospitalization rates (HR = 0.96, 95% CI 0.55 to 1.69 and HR = 1.26, 95% CI 0.73 to 2.17, respectively). However, patients with small annuli had consistently higher mean and peak pressure gradients and a higher risk of patient-prosthesis mismatch. The risks of moderate-to-severe regurgitation and structural valve deterioration were similar between the three groups. In conclusion, although patients with small annuli had higher transvalvular gradients, there was no significant association between the aortic annulus size and TAVI clinical outcomes at 3 years of follow-up. Future studies should compare the performance of transcatheter valve types in patients with different aortic annulus sizes.

Consensus recommendations for COVID-19-related myocarditis in athletes: proof of concept-case report.

Background: Post-viral myocarditis has been associated with sudden cardiac death in athletes. Since the beginning of the COVID-19 pandemic, the concern of post-viral myocarditis impacting the professional athletic community has been present. Case summary: An elite-level basketball player presented after a positive COVID-19 test with findings consistent with ventricular tachycardia related to myocardial fibrosis/scar from a COVID-19-related myocarditis. Although rare, COVID-19 myocarditis can occur. This case illustrates how the consensus guidelines for return-to-play correctly identified the player as high risk with appropriate downstream evaluation by cardiac magnetic resonance (CMR) imaging. The stepwise approach is illustrated in this case and highlights the utility and success of the algorithm when approaching athletes with COVID-19-related myocarditis risk and determining a return to exercise. Discussion: Diligence is required to identify competitive athletes with features suggestive of myocarditis at the initial presentation and with the return to exercise. Cardiopulmonary symptoms in the setting of recent COVID-19 infection should prompt additional testing in a stepwise fashion and often benefit from CMR in addition to the triad testing with electrocardiography, echocardiography, and cardiac troponin measurement to further investigate clinical presentations of COVID-19-related myocarditis.

The impact of catheter ablation in patient's heart failure and atrial fibrillation: a meta-analysis of randomized clinical trials.

BACKGROUND: Recent trial data suggest a benefit to catheter ablation (CA) compared to medical therapy for atrial fibrillation (AF) in patients with heart failure (HF). Nevertheless, because of mixed trial evidence, contemporary guidelines give it a class 2 recommendation. Accordingly, we sought to assess the currently available evidence for CA in HF with AF. METHODS: Electronic databases were searched to identify randomized clinical trials (RCTs) comparing CA to medical therapy in patients with AF and HF. Study data was pooled using fixed and random effects, and the number needed to treat (NNT) was calculated to gauge absolute risk differences. Heterogeneity was quantified using I2. Our primary outcome was all-cause mortality. RESULTS: Nine trials (CA 1075 patients; medical therapy 1083 patients) were included. Ablation reduced the relative risk of all-cause mortality by 31.5% (95% CI 13.7 to 45.6%; NNT = 23), cardiovascular mortality by 39.3% (95% CI 10.9 to 58.7%; NNT = 31), cardiovascular hospitalization by 29.1% (95% CI 9.4 to 44.6%; NNT = 9), and heart failure hospitalization by 28.5% (95% CI 6.5 to 45.4%; NNT = 22). Improvements in quality of life were observed with CA using the Minnesota Living with Heart Failure Questionnaire (mean difference - 5.26; 95% CI - 2.73 to - 7.78) and the Atrial Fibrillation Effect on Quality of Life (mean difference 5.36; 95% CI 2.72 to 8.00). CONCLUSION: Compared to medical therapy, CA for AF in patients with HF reduces all-cause mortality, cardiovascular mortality, cardiovascular hospitalizations, and heart failure hospitalizations, and may improve quality of life.

Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

BACKGROUND: Since the initial clinical description of hypertrophic cardiomyopathy (HCM) over 60 years ago, sudden cardiac death (SCD) has been the most visible and feared complication of HCM. OBJECTIVES: This study sought to characterize the temporal, geographic, and age-related trends of reported SCD rates in adult HCM patients. METHODS: Electronic databases were systematically searched up to November 2021 for studies reporting on SCD event rates in HCM patients. Patients with SCD equivalents (appropriate implantable cardioverter-defibrillator [ICD] shocks and nonfatal cardiac arrests) were not included. A random-effects model was used to pool study estimates calculating the overall incidence rates (IR) for each time-era, geographic region, and age group. We analyzed 2 periods (before vs after 2000, following clinical implementation of ICD in HCM). Following 2000, 5-year intervals were used to demonstrate the temporal change in SCD rates. RESULTS: A total of 98 studies (N = 70,510 patients and 431,407 patient-years) met our inclusion criteria. The overall rate of HCM SCD was 0.43%/y (95% CI: 0.37-0.50%/y; I2 = 75%; SCD events: 1,938; person-years of follow-up: 408,715), with young patients (<18 years of age) demonstrating a >2-fold-risk for sudden death vs adult patients 18-60 years of age (IR: 1.09%; 95% CI: 0.69%-1.73% vs IR: 0.43%; 95% CI: 0.37%-0.50%) (P value for subgroup differences <0.01). Contemporary SCD rates from 2015 to present were 0.32%/y and significantly lower compared with 2000 or earlier (IR: 0.32%; 95% CI: 0.20%-0.52% vs IR: 0.73%; 95% CI: 0.53%-1.02%, respectively). Reported SCD rates for HCM were lowest in North America (IR: 0.28%; 95% CI: 0.18%-0.43%,) and highest in Asia (IR: 0.67%; 95% CI: 0.54%-0.84%). CONCLUSIONS: Contemporary HCM-related SCD rates are low (0.32%/y) representing a 2-fold decrease compared with prior treatment eras. Young HCM patients are at the highest risk. The maturation of SCD risk stratification strategies and the application of primary prevention ICD to HCM are likely responsible for the notable decline over time in SCD events. In addition, worldwide geographic disparities in SCD rates were evident, underscoring the need to increase access to SCD prevention treatment for all HCM patients.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Radiation reduction in a modern catheterization laboratory: A single-center experience.

BACKGROUND: Measures were undertaken at the Cleveland Clinic to reduce radiation exposure to patients and personnel working in the catheterization laboratories. We report our experience with these improved systems over a 7-year period in patients undergoing diagnostic catheterization (DC) and percutaneous coronary interventions (PCIs). METHODS: Patients were categorized into preinitiative (2009-2012) and postinitiative (2013-2019) groups in the DC and PCI cohorts. Propensity score matching was done between the pre- and postinitiative groups for both cohorts based on age, sex, body surface area, total fluoroscopy time, and total acquisition time. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (Ka,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups. RESULTS: In the DC cohort, there was a significant reduction in Ka,r in the postinitiative group in comparison to the preinitiative group (median, 396 vs. 857 mGy; p < 0.001). In the PCI cohort, Ka,r in the postinitiative group was 1265 mGy, which was significantly lower than the corresponding values in the preinitiative group (1994 mGy; p < 0.001). We also observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates, and air kerma area product in the postinitiative group in comparison to the preinitiative group in both matched and unmatched DC and PCI cohorts after the institution of radiation reduction measures. CONCLUSION: There was a significant and sustained reduction in radiation exposure to patients in the catheterization laboratory with the implementation of advanced protocols. Similar algorithms can be applied in other laboratories to achieve a similar reduction in radiation exposure.

Meta-Analysis of Provisional Versus Systematic Double-Stenting Strategy for Left Main Bifurcation Lesions.

OBJECTIVE: We sought to compare the clinical outcomes with provisional versus double-stenting strategy for left main (LM) bifurcation percutaneous coronary intervention (PCI). BACKGROUND: Despite two recent randomized controlled trials (RCTs) and several observational reports, the optimal LM bifurcation PCI technique remains controversial. METHODS: PubMed, Cochrane Central Register of Controlled-Trials (CENTRAL), Clinicaltrials.gov, International Clinical Trial Registry Platform were leveraged for studies comparing PCI bifurcation techniques for LM coronary lesions using second-generation drug eluting stents (DES). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), target vessel or lesion revascularization, and stent thrombosis. RESULTS: Two RCTs and 10 observational studies with 7105 patients were included. Median follow-up duration was 42 months (IQR: 25.7). Double stenting was associated with a trend towards higher incidence of MACE (odds ratio [OR] 1.20; 95 % confidence interval [CI] 0.94 to 1.53) compared with provisional stenting. This was mainly driven by higher rates of target lesion revascularization (TLR) (OR 1.50; 95 % CI 1.07 to 2.11). There were no statistically significant differences in the incidence of all-cause mortality, cardiovascular mortality, MI, or stent thrombosis. On subgroup analysis according to the study type, provisional stenting was associated with lower MACE and TLR in observational studies, but not in RCTs. CONCLUSION: For LM bifurcation PCI using second-generation DES, a provisional stenting strategy was associated with a trend towards lower incidence of MACE driven by statistically significant lower rates of TLR, compared with systematic double stenting. These differences were primarily driven by observational studies. Further RCTs are warranted to confirm these findings.

Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis.

BACKGROUND: Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown. METHODS: Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). RESULTS: Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%). CONCLUSION: Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

Fixed-Dose Combination (Polypill) for Cardiovascular Disease Prevention: A Meta-Analysis.

INTRODUCTION: This meta-analysis was performed to assess the efficacy of fixed-dose combination (polypill) in reducing the risk of mortality and cardiovascular events. METHODS: Medline, Scopus, Web of Science, and Cochrane Central were searched during May 2021. All randomized trials investigating the efficacy of antihypertensive and lipid-lowering ± antiplatelet drug combinations in patients at cardiovascular risk were included. Outcomes were presented as risk ratios or standardized mean differences with 95% CIs. RESULTS: A total of 16 trials (N = 26,567 participants) were included. The risk reduction for all-cause mortality (risk ratio = 0.90; 95% CI = 0.79, 1.01; I2 = 0%; moderate certainty) and major adverse cardiac events (risk ratio=0.84; 95% CI=0.68, 1.04; I2=51%; very low certainty) did not reach statistical significance in comparison with those of the control group. Subgroup analysis of studies that used an active control yielded similar results. However, significant reductions in major adverse cardiac event risk were observed in studies that exclusively targeted primary prevention, followed patients for ≥4 years, and had a low risk of bias. The polypill group had significantly higher adherence (risk ratio=1.18; 95% CI=1.06, 1.32; I2=96%; very low certainty) and comprable rates of adverse side effects (risk ratio=1.10; 95% CI=0.98, 1.23; I2=58%; moderate certainty) with those of the control group. Patients randomized to the polypill had significant reductions in systolic and diastolic blood pressure as well as in total and low-density lipoprotein cholesterol. DISCUSSION: Despite reductions in cardiovascular risk factors, the observed mortality benefit for the polypill did not reach statistical significance. Further studies are needed to validate its clinical benefits and determine the patient populations likely to achieve such benefits.