Cardiac paragangliomas: A case series with clinicopathologic features and succinate dehydrogenase B immunostaining.

Cardiac paragangliomas (PGs) are very rare tumors that comprise less than 1% of all cardiac tumors. PGs can occur sporadically, but inherited syndromes may also play a role in the development of PGs. Approximately one-third of PGs are associated with mutations in the succinate dehydrogenase (SDH) complex, specifically SDHB, as part of syndrome-associated PGs or sporadic PGs. SDH mutations have been assessed by SDHB immunohistochemistry, as negative staining indicates a high likelihood of mutation in PGs in other sites, but not in cardiac PGs. This study aims to evaluate the clinical and pathologic characteristic of cardiac PG cases and assess the expression of SDHB by immunohistochemistry. A retrospective chart analysis of 10 patients with cardiac PG was performed to assess the patient age, sex, size, site of the tumor, and clinical symptoms. Histologically the tumors showed the classic pattern of nested tumor cells surrounded by sustentacular cells. Immunohistochemistry for SDHB was performed in five cases. One case showed a complete absence of SDHB immunohistochemical staining and the others showed staining ranging from a weak-to-strong granular cytoplasmic staining pattern. We conclude that SDHB immunostaining is cost-effective in identifying cases with SDH mutation. It is recommended to assess SDH mutation in patients with cardiac PG to predict the aggressive behavior that has been reported by previous studies from PGs of other sites.

Primary cardiac sarcomas: Treatment strategies.

OBJECTIVE: Our multidisciplinary cardiac tumor team now has an experience of operating on 122 cases of primary cardiac sarcoma over a 23-year period. The purpose of this study is to present our short- and long-term outcomes for cardiac sarcoma. METHODS: We performed a retrospective review of a prospectively collected Institutional Review Board-approved cardiac tumor database for cardiac sarcoma. Patient characteristics, surgical factors, and patient outcomes were analyzed. Perioperative data were collected from direct patient communication and all available medical records. The primary end point was all-cause mortality at 1, 3, and 5 years from the time of our surgery and 1, 3, and 5 years from the initial diagnosis. The secondary end point was all-cause mortality between the first and second halves of the study. RESULTS: From October 1998 to April 2021, we operated on 122 patients with a primary cardiac sarcoma. The mean age was 45.3 years old, and 52.5% were male. Tumors were most frequently found in the left atrium (40.2%) and right atrium (32.0%). The most common type of tumor histologically was an angiosarcoma (38.5%), followed by high-grade sarcoma (14.8%). Survival from initial diagnosis at 1, 3, and 5 years was 88.4%, 43.15%, and 27.8%, respectively. Survival from surgery at our institution at 1 and 3 years was 57.1% and 24.5%, respectively. When comparing outcomes from different time periods, we found no significant difference in survival between the previous era (1998-2011) and the current era (2011-2021). CONCLUSIONS: Management of these complex patients can show reasonable outcomes in centers with a multidisciplinary cardiac tumor team. Mortality has not improved with time and is likely related to the systemic nature of this disease.

Coronary vein defibrillator coil placement in patients with high defibrillation thresholds.

BACKGROUND: Elevated defibrillation threshold (DFT) occurs in 2%-6% of patients undergoing implantable cardioverter defibrillator (ICD) implantation. Adding a defibrillation coil in the coronary sinus (CS) or its branches can result in substantial reductions in the mean DFT. However, data regarding acute success and long-term stability remain lacking. We report our experience with this bailout strategy. METHODS: Patients with elevated DFT at implantation (safety margin at implantation <10 J) and those with failed ICD shocks for ventricular arrhythmias (VA) referred for high DFT underwent placement of an additional defibrillation coil in the CS. DFT testing was performed at the completion of the implantation procedure. External potentially reversible factors were excluded. High-output devices were systematically used. RESULTS: Four patients with high DFT at implantation and two with several failed shock attempts underwent placement of a defibrillation coil in the CS. Mean age was 41.8 (23-78). They presented a mean LVEF of 21% (15-30), QRS-complex duration of 109.8 milliseconds (87-168), body surface area of 1.96 m2 (1.45-2.58), and a mean R wave of 16.3 mV (8-27). Defibrillation coil implantation in the CS (final shocking configuration of right ventricle as anode and left ventricle (LV) plus can as cathode) was associated with successful DFT testing in all. Three patients had a concomitant LV lead for biventricular pacing. During a mean follow-up of 54.67 months (10-118), two patients experienced successful ICD shocks for VA (one of them also presented inappropriate shocks because of the fast conducting atrial fibrillation). CONCLUSIONS: Positioning of a defibrillation coil in the CS can result in a substantial reduction in mean DFT and associates with optimal long-term stability.

NS5806 Induces Electromechanically Discordant Alternans and Arrhythmogenic Voltage-Calcium Dynamics in the Isolated Intact Rabbit Heart.

Background: NS5806 activates the transient outward potassium current I to, and has been claimed to reproduce Brugada Syndrome (BrS) in ventricular wedge preparations. I to modulates excitation-contraction coupling, which is critical in alternans dynamics. We explored NS5806-arrhythmogenic effects in the intact whole heart and its impact on alternans. Methods: Langendorff-perfused rabbit hearts (n = 20) underwent optical AP and Ca mapping during pacing at decremental cycle lengths (CL). Spontaneous arrhythmias and pacing-induced alternans was characterized at baseline (BL), after perfusing with NS5806, before and after adding verapamil (VP), and SEA0400 (SEA, n = 5 each), to modulate Ca-current and Na-Ca exchange, the main AP-Ca coupling mechanisms. Results: NS5806 induced BrS-like ECG features in 6 out of 20 hearts. NS5806 prolonged steady-state (3 Hz) action potential duration (APD) by 16.8%, Ca decay constant by 34%, and decreased conduction velocity (CV) by 52.6%. After NS5806 infusion, spontaneous ventricular ectopy (VE) and AP/Ca alternans occurred. Pacing-induced alternans during NS5806 infusion occurred at longer CL and were AP/Ca discordant from its onset. Spatially discordant alternans after NS5806 infusion had non-propagation-driven nodal line distribution. No spontaneous phase-2 reentry occurred. Under NS5806 + VP, alternans became AP/Ca concordant and only induced in two out of five; NS5806 + SEA did not affect alternans but suppressed spontaneous ectopy. Conclusions: NS5806 disrupts AP-Ca coupling and leads to Ca-driven, AP/Ca-discordant alternans and VE. Despite BrS-like ECG features, no spontaneous sustained arrhythmias or phase-2 reentry occurred. NS5806 does not fully reproduce BrS in the intact rabbit heart.

Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea: Implications for Atrial Fibrillation.

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.

Incidence and outcomes of cancer treatment-related cardiomyopathy among referrals for advanced heart failure.

BACKGROUND: Approximately 2-3% of patients undergoing advanced heart failure therapies such as left ventricular assist devices (LVAD) and orthotropic heart transplantation (OHT) have chemotherapy-related cardiomyopathy, according to analyses of large databases such as United Network for Organ Sharing (UNOS) or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registries. While these studies have shown similar survival outcomes post-interventions, these databases by definition exclude patients referred for advanced therapies but do not receive them, and thus there is little data on overall outcomes of such patients. Given the lack of nuance in the diagnoses in large registries and the possibility that many cancer treatment-related cardiomyopathy (CCMP) patients might be misclassified by the generic "non-ischemic" or "dilated" cardiomyopathies, we investigated the incidence and clinical outcomes of CCMP patients among advanced heart failure (HF) referrals at a single high volume institution. METHODS: All referrals from 2013 to 2016 were evaluated for type of cardiomyopathy, with careful chart review. Outcomes such as LVAD, OHT and death were compared between CCMP and other cardiomyopathies. RESULTS: Of 553 referrals for advanced HF, 19 (3.4%) were for CCMP. There was a higher percentage of patients receiving advanced therapies in the CCMP vs. non-ischemic cardiomyopathy (NICMP) and ischemic cardiomyopathy (ICMP) (42.1% vs 30.2% vs 33.6%, not significant). Of the CCMP patients, 3 had OHT directly, 2 had LVAD followed by OHT, and 3 had LVADs as bridge to candidacy or destination therapy. Fifty-eight percent of the CCMP did not receive LVAD or OHT compared to 69.8% and 66.3 of the NICMP and ICMP, respectively (p = 0.0388). Independent of type of advanced therapy, survival was significantly higher in the CCMP group compared to NICMP and ICMP (93.3% vs 84.8% vs 73.8%, respectively P = 0.0021 for 1 year, 93.3% vs 76.2% vs 58.3%, respectively, P = < 0.0001 for 3 year). CONCLUSIONS: In a single institution, CCMP accounts for more than 3% of all referrals for advanced HF therapies and almost 8% of NICMP. Contrary to concerns for previous cancer and sequelae of cancer treatment excluding patients for advanced therapies, a higher percentage of CCMP underwent advanced HF therapies and with similar outcomes. This is the first study to show that among patients referred for advanced therapies, CCMP patients do not have inferior outcomes compared to other cardiomyopathies regardless of the selected management strategy.